Search in electronic databases (n=1558) PubMed: 760 Embase: 795 Web of Science: 3

Search in electronic databases (n=1558)PubMed: 760Embase: 795Web of Science: 3

Retrieved (n=1579)

Hand-searching(n=21)

Title review (n=782)

Abstract review (n=341)

Article review for more detailed evaluation (n=117)

Included 79 studies in 75 articles

Excluded duplicates(n=797)

Excluded; no relevance(n=441)

Articles excluded (n=42)For reasons see Supplementary Table 1

Supplementary Figure 1. Study flow diagram

Supplementary Figure 2. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. All studies.

Random effectFixed effect

Hugot JP (2001)

Hampe J (2002)

Study

Ernst A (2007)Cavanaugh JA (2003)

Canto E (2007)

Heresbach D (2004)

Karban A (2005)

Nunez C (2004)

Newman B (2004)

Karban A (2005)

Arnot IDR (2004)

Tukel T (2004)Ince AT (2008)

Weersma RK (2009)

Leung E (2005)

Bene J (2006)

Oostenbrug LE (2006)

Jess T (2005)

Vermeire S (2002)

Ahmad T (2002)

Zouiten-Mekki L (2005)

Cottone M (2006)

Riss L (2007)

Giachino D (2004)

Brant SR (2007)

Ferraris A (2006)

Lakatos PL (2005)Baptista ML (2008)

Vermeire S (2004)

Crawford NPS (2007)

Protic MB (2007)

Esters N (2004)

Mendoza JL (2003)

Russel RK (2005)Cukovic-Cavak S (2006)

Tomer G (2003)

Lappalainen M (2008)

Sugimura K (2003)

Economou M (2007)

Torkvist L (2006)

van der Linde K (2007)

Tukel T (2004)

Braat H (2005)Diego CD (2006)

Nagy Z (2005)

Magyari L (2009)

Vind I (2005)

de Ridder L (2007)

Cucchiara S (2007)Kugathasan S (2005)

Bonen DK (2003)

Bianchi V (2007)

Buhner S (2006)Karban A (2004)

Zhou Z (2002)

Hradsky O (2008)

Cuthbert AP (2002)

Rigoli L (2008)

Ozen SC (2006)

Annese V (2005)

Buning C (2005)

Gazouli M (2004)

Helio T (2003)

Rodrigo L (2007)

Zaahl MG (2005)

Vavassori P (2004)

Kugathasan S (2005)

Mascheretti S (2002)

Ferreira AC (2005)

Kugathasan S (2005)

Derakhshan F (2008)

Gearry RB (2007)

2.24 (2.03, 2.48)

3.06 (1.47, 6.39)

2.72 (1.92, 3.84)

2.02 (1.32, 3.09)2.35 (1.56, 3.56)

6.59 (1.52, 28.55)

2.60 (1.25, 5.43)

4.24 (1.46, 12.30)

1.17 (0.62, 2.20)

2.26 (1.31, 3.90)

5.58 (0.23, 137.89)

1.48 (0.88, 2.51)

6.71 (1.04, 43.16)0.16 (0.02, 1.26)

1.65 (1.33, 2.04)

1.47 (0.80, 2.69)

1.89 (0.58, 6.10)

1.88 (1.21, 2.92)

3.76 (1.11, 12.80)

3.38 (1.43, 8.01)

2.63 (1.71, 4.04)

3.51 (0.41, 30.30)

OR (95% CI)

2.98 (1.33, 6.70)

2.31 (1.50, 3.57)

1.56 (0.89, 2.76)

3.49 (2.08, 5.86)

4.51 (1.91, 10.64)

2.55 (1.37, 4.73)3.77 (2.00, 7.10)

2.94 (1.74, 4.96)

5.50 (1.67, 18.18)

1.50 (0.90, 2.50)

2.42 (1.48, 3.97)

3.52 (1.70, 7.26)

1.19 (0.58, 2.43)2.79 (1.35, 5.76)

5.47 (1.48, 20.16)

2.15 (0.83, 5.55)

1.73 (1.10, 2.73)

3.85 (1.25, 11.93)

6.68 (1.52, 29.31)

1.53 (0.68, 3.45)

2.11 (0.92, 4.84)

2.89 (1.47, 5.65)2.29 (1.15, 4.58)

2.30 (1.00, 5.27)

1.41 (0.66, 3.03)

1.01 (0.41, 2.49)

2.96 (1.77, 4.93)

3.01 (1.83, 4.95)1.26 (0.76, 2.07)

1.95 (1.26, 3.04)

1.79 (0.94, 3.42)

3.15 (1.06, 9.32)4.13 (1.38, 12.34)

1.13 (0.56, 2.26)

1.48 (0.95, 2.30)

2.72 (1.64, 4.50)

4.36 (1.64, 11.55)

0.75 (0.14, 4.17)

2.20 (1.26, 3.85)

2.81 (1.33, 5.92)

11.00 (2.57, 47.14)

1.84 (0.86, 3.93)

0.79 (0.36, 1.72)

2.10 (0.62, 7.08)

1.52 (0.28, 8.37)

0.53 (0.06, 4.80)

2.05 (1.33, 3.14)

3.31 (2.03, 5.38)

0.44 (0.02, 7.89)

9.51 (3.00, 30.16)

2.59 (1.41, 4.76)

1.31

2.97

2.502.57

0.42

1.31

0.73

1.61

1.93

0.09

2.02

0.270.22

3.81

1.71

0.62

2.44

0.58

1.04

2.48

0.20

Weight, %

1.14

2.46

1.85

2.05

1.04

1.661.61

2.03

0.60

2.08

2.16

1.34

1.371.34

0.52

0.89

2.35

0.66

0.41

1.13

1.09

1.491.43

1.10

1.24

0.96

2.08

2.142.14

2.42

1.57

0.710.70

1.42

2.43

2.11

0.85

0.32

1.88

1.29

0.42

1.25

1.20

0.59

0.32

0.20

2.50

2.20

0.12

0.64

1.69

2.24 (2.03, 2.48)

3.06 (1.47, 6.39)

2.72 (1.92, 3.84)

2.02 (1.32, 3.09)2.35 (1.56, 3.56)

6.59 (1.52, 28.55)

2.60 (1.25, 5.43)

4.24 (1.46, 12.30)

1.17 (0.62, 2.20)

2.26 (1.31, 3.90)

5.58 (0.23, 137.89)

1.48 (0.88, 2.51)

6.71 (1.04, 43.16)0.16 (0.02, 1.26)

1.65 (1.33, 2.04)

1.47 (0.80, 2.69)

1.89 (0.58, 6.10)

1.88 (1.21, 2.92)

3.76 (1.11, 12.80)

3.38 (1.43, 8.01)

2.63 (1.71, 4.04)

3.51 (0.41, 30.30)

2.98 (1.33, 6.70)

2.31 (1.50, 3.57)

1.56 (0.89, 2.76)

3.49 (2.08, 5.86)

4.51 (1.91, 10.64)

2.55 (1.37, 4.73)3.77 (2.00, 7.10)

2.94 (1.74, 4.96)

5.50 (1.67, 18.18)

1.50 (0.90, 2.50)

2.42 (1.48, 3.97)

3.52 (1.70, 7.26)

1.19 (0.58, 2.43)2.79 (1.35, 5.76)

5.47 (1.48, 20.16)

2.15 (0.83, 5.55)

1.73 (1.10, 2.73)

3.85 (1.25, 11.93)

6.68 (1.52, 29.31)

1.53 (0.68, 3.45)

2.11 (0.92, 4.84)

2.89 (1.47, 5.65)2.29 (1.15, 4.58)

2.30 (1.00, 5.27)

1.41 (0.66, 3.03)

1.01 (0.41, 2.49)

2.96 (1.77, 4.93)

3.01 (1.83, 4.95)1.26 (0.76, 2.07)

1.95 (1.26, 3.04)

1.79 (0.94, 3.42)

3.15 (1.06, 9.32)4.13 (1.38, 12.34)

1.13 (0.56, 2.26)

1.48 (0.95, 2.30)

2.72 (1.64, 4.50)

4.36 (1.64, 11.55)

0.75 (0.14, 4.17)

2.20 (1.26, 3.85)

2.81 (1.33, 5.92)

11.00 (2.57, 47.14)

1.84 (0.86, 3.93)

0.79 (0.36, 1.72)

2.10 (0.62, 7.08)

1.52 (0.28, 8.37)

0.53 (0.06, 4.80)

2.05 (1.33, 3.14)

3.31 (2.03, 5.38)

0.44 (0.02, 7.89)

9.51 (3.00, 30.16)

2.59 (1.41, 4.76)

1.31

2.97

2.502.57

0.42

1.31

0.73

1.61

1.93

0.09

2.02

0.270.22

3.81

1.71

0.62

2.44

0.58

1.04

2.48

0.20

1.14

2.46

1.85

2.05

1.04

1.661.61

2.03

0.60

2.08

2.16

1.34

1.371.34

0.52

0.89

2.35

0.66

0.41

1.13

1.09

1.491.43

1.10

1.24

0.96

2.08

2.142.14

2.42

1.57

0.710.70

1.42

2.43

2.11

0.85

0.32

1.88

1.29

0.42

1.25

1.20

0.59

0.32

0.20

2.50

2.20

0.12

0.64

1.69

1.05 1 5 10 50

Crohn’s disease

Odds ratio (95% CI)

2.21 (2.06, 2.37)

Supplementary Figure 3. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Crohn’s disease. All studies.

Random effectFixed effect

Vind I (2005)

Ince AT (2008)

Ferreira AC (2005)

Sugimura K (2003)


Buhner S (2006)

Torkvist L (2006)

Ferraris A (2006)

Tukel T (2004)

Bonen DK (2003)

Tomer G (2003)

Kugathasan S (2005)

Canto E (2007)

Protic MB (2007)

Braat H (2005)

Annese V (2005)

Esters N (2004)

Magyari L (2009)

Ernst A (2007)

Newman B (2004)

Leung E (2005)

Rigoli L (2008)

Rodrigo L (2007)

Kugathasan S (2005)

Riss L (2007)Lakatos PL (2005)

Jess T (2005)

Cukovic-Cavak S (2006)

Vermeire S (2002)

Nunez C (2004)

Study

Crawford NPS (2007)

Cavanaugh JA (2003)


Karban A (2004)


Hradsky O (2008)

Baptista ML (2008)

Ozen SC (2006)

Ahmad T (2002)

Diego CD (2006)Buning C (2005)

Arnot IDR (2004)

Derakhshan F (2008)

Cuthbert AP (2002)

Bene J (2006)

Mendoza JL (2003)

Cucchiara S (2007)

Hugot JP (2001)


Giachino D (2004)

Heresbach D (2004)

Zaahl MG (2005)

Gazouli M (2004)

Hampe J (2002)

de Ridder L (2007)

Bianchi V (2007)

Zhou Z (2002)

Queiroz DM, (2009)

Karban A (2005)

Weersma RK (2009)

Brant SR (2007)

Karban A (2005)

Vavassori P (2004)

Kugathasan S (2005)

Vermeire S (2004)

Cottone M (2006)

Nagy Z (2005)


Helio T (2003)

Economou M (2007)

Gearry RB (2007)

Russel RK (2005)

Tukel T (2004)

2.56 (2.23, 2.94)

3.11 (0.69, 14.06)

0.65 (0.06, 7.21)

OR (95% CI)

2.19 (0.90, 5.33)

1.58 (0.95, 2.63)

1.99 (0.70, 5.63)

2.63 (0.57, 12.19)

12.30 (0.70, 216.21)

6.89 (2.33, 20.32)

2.50 (1.30, 4.78)

3.31 (1.80, 6.10)

1.96 (0.98, 3.93)

4.27 (2.23, 8.17)

5.83 (0.32, 106.57)

20.60 (1.22, 347.57)

1.11 (0.59, 2.09)

2.85 (1.46, 5.56)

3.43 (1.47, 7.97)

8.20 (1.83, 36.73)

1.55 (0.73, 3.29)

1.52 (0.80, 2.91)

1.48 (0.62, 3.50)

1.03 (0.43, 2.50)

1.20 (0.24, 5.99)

0.96 (0.05, 18.98)

1.21 (0.53, 2.76)1.76 (0.77, 4.02)

2.31 (0.38, 14.24)

4.15 (0.92, 18.78)

7.73 (1.04, 57.63)

5.19 (1.49, 18.10)

2.30 (0.66, 8.06)

2.13 (0.85, 5.33)

3.98 (0.19, 83.06)

7.00 (3.12, 15.69)

9.88 (1.29, 75.93)

2.82 (1.55, 5.12)

1.20 (0.43, 3.33)

2.30 (0.38, 13.94)

2.33 (1.05, 5.18)

2.63 (0.83, 8.35)2.58 (0.85, 7.77)

7.10 (0.93, 54.19)

5.21 (0.94, 29.04)

6.71 (2.03, 22.14)

6.28 (0.78, 50.38)

4.64 (1.62, 13.25)

2.97 (1.63, 5.42)

6.49 (1.57, 26.82)

1.42 (0.83, 2.45)

3.17 (1.15, 8.76)

2.37 (0.68, 8.28)

0.81 (0.03, 19.99)

4.55 (1.97, 10.51)

5.72 (2.91, 11.25)

1.31 (0.78, 2.22)

4.79 (1.37, 16.71)

1.57 (0.84, 2.94)

5.23 (1.61, 17.04)

1.87 (0.37, 9.39)

2.05 (1.49, 2.82)

4.06 (1.69, 9.73)

5.76 (2.59, 12.81)

2.66 (0.97, 7.31)2.10 (0.81, 5.42)

4.01 (1.61, 9.99)

1.95 (0.43, 8.86)

2.52 (1.41, 4.51)

7.79 (0.40, 151.18)

0.84 (0.39, 1.79)

2.21 (0.86, 5.65)

11.20 (0.64, 197.01)

7.52 (1.90, 29.85)

0.72

0.31

1.64

3.00

1.31

0.70

0.22

1.24

2.40

2.55

2.23

2.40

0.22

0.23

2.45

2.32

1.76

0.73

2.03

2.40

1.71

1.65

0.65

0.21

1.801.81

0.52

0.72

0.43

0.99

0.98

1.57

0.20

1.86

0.42

2.61

1.35

0.53

1.89

1.121.20

0.43

0.58

1.06

0.41

1.29

2.59

0.80

2.85

1.36

0.99

0.18

1.78

2.29

2.94

0.99

2.49

1.08

0.64

3.99

1.68

1.89

1.37

0.00

1.50

1.58

0.72

2.68

0.21

2.00

1.52

0.22

0.84

2.56 (2.23, 2.94)

3.11 (0.69, 14.06)

0.65 (0.06, 7.21)

2.19 (0.90, 5.33)

1.58 (0.95, 2.63)

1.99 (0.70, 5.63)

2.63 (0.57, 12.19)

12.30 (0.70, 216.21)

6.89 (2.33, 20.32)

2.50 (1.30, 4.78)

3.31 (1.80, 6.10)

1.96 (0.98, 3.93)

4.27 (2.23, 8.17)

5.83 (0.32, 106.57)

20.60 (1.22, 347.57)

1.11 (0.59, 2.09)

2.85 (1.46, 5.56)

3.43 (1.47, 7.97)

8.20 (1.83, 36.73)

1.55 (0.73, 3.29)

1.52 (0.80, 2.91)

1.48 (0.62, 3.50)

1.03 (0.43, 2.50)

1.20 (0.24, 5.99)

0.96 (0.05, 18.98)

1.21 (0.53, 2.76)1.76 (0.77, 4.02)

2.31 (0.38, 14.24)

4.15 (0.92, 18.78)

7.73 (1.04, 57.63)

5.19 (1.49, 18.10)

2.30 (0.66, 8.06)

2.13 (0.85, 5.33)

3.98 (0.19, 83.06)

7.00 (3.12, 15.69)

9.88 (1.29, 75.93)

2.82 (1.55, 5.12)

1.20 (0.43, 3.33)

2.30 (0.38, 13.94)

2.33 (1.05, 5.18)

2.63 (0.83, 8.35)2.58 (0.85, 7.77)

7.10 (0.93, 54.19)

5.21 (0.94, 29.04)

6.71 (2.03, 22.14)

6.28 (0.78, 50.38)

4.64 (1.62, 13.25)

2.97 (1.63, 5.42)

6.49 (1.57, 26.82)

1.42 (0.83, 2.45)

3.17 (1.15, 8.76)

2.37 (0.68, 8.28)

0.81 (0.03, 19.99)

4.55 (1.97, 10.51)

5.72 (2.91, 11.25)

1.31 (0.78, 2.22)

4.79 (1.37, 16.71)

1.57 (0.84, 2.94)

5.23 (1.61, 17.04)

1.87 (0.37, 9.39)

2.05 (1.49, 2.82)

4.06 (1.69, 9.73)

5.76 (2.59, 12.81)

2.66 (0.97, 7.31)

2.10 (0.81, 5.42)

4.01 (1.61, 9.99)

1.95 (0.43, 8.86)

2.52 (1.41, 4.51)

7.79 (0.40, 151.18)

0.84 (0.39, 1.79)

2.21 (0.86, 5.65)

11.20 (0.64, 197.01)

7.52 (1.90, 29.85)

0.72

0.31

1.64

3.00

1.31

0.70

0.22

1.24

2.40

2.55

2.23

2.40

0.22

0.23

2.45

2.32

1.76

0.73

2.03

2.40

1.71

1.65

0.65

0.21

1.801.81

0.52

0.72

0.43

0.99

0.98

1.57

0.20

1.86

0.42

2.61

1.35

0.53

1.89

1.121.20

0.43

0.58

1.06

0.41

1.29

2.59

0.80

2.85

1.36

0.99

0.18

1.78

2.29

2.94

0.99

2.49

1.08

0.64

3.99

1.68

1.89

1.37

0.00

1.50

1.58

0.72

2.68

0.21

2.00

1.52

0.22

0.84

1.05 5 10 50

Crohn’s disease Weight, %

Odds ratio (95% CI)

(Excluded)

2.56 (2.31, 2.83)

Studies were excluded from meta-analysis if the risk allele/genotype was found neither in cases nor in controls.

Supplementary Figure 4. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. All studies..

Random effect

Fixed effect

Ahmad T (2002)

Gearry RB (2007)Hugot JP (2001)

Arnot IDR (2004)

Buning C (2005)

Economou M (2007)

Tomer G (2003)Helio T (2003)


Crawford NPS (2007)


Heresbach D (2004)

Ogura Y (2001)

Cuthbert AP (2002)

Weersma RK (2009)

Vermeire S (2002)

Vind I (2005)

Zaahl MG (2005)

Cavanaugh JA (2003)

Hampe J (2002)

Lakatos PL (2005)

Roussomoustakaki M (2003)

Mendoza JL (2003)

Rodrigo L (2007)


Ferreira AC (2005)

Sugimura K (2003)

Murillo L (2002)


Protic MB (2007)

Kugathasan S (2005)

Karban A (2005)

Bene J (2006)

Ernst A (2007)

Radlmayr M (2002)

Baptista ML (2008)

Karban A (2004)

Hampe J (2001)

Vermeire S (2004)

Gazouli M (2004)

Karban A (2005)Rigoli L (2008)

Zhou Z (2002)

Magyari L (2009)

Bonen DK (2003)

Diego CD (2006)

Tukel T (2004)

Guo QS (2004)

Kugathasan S (2005)

Ozen SC (2006)

Ferraris A (2006)

Giachino D (2004)


Annese V (2005)

Nagy Z (2005)

Leung E (2005)

Newman B (2004)

Canto E (2007)

Derakhshan F (2008)

Buhner S (2006)

Cucchiara S (2007)

Cottone M (2006)

Queiroz DM, (2009)

Torkvist L (2006)

Study

Riss L (2007)

Russel RK (2005)

de Ridder L (2007)

Esters N (2004)

Nunez C (2004)

Tukel T (2004)

Ince AT (2008)

Hradsky O (2008)

Vavassori P (2004)

Kugathasan S (2005)

Jess T (2005)

Braat H (2005)


Brant SR (2007)

Bianchi V (2007)

3.84 (3.41, 4.32)

6.50 (3.33, 12.68)

4.17 (1.50, 11.57)6.86 (2.50, 18.83)

3.86 (1.35, 11.03)

5.48 (2.57, 11.67)

7.06 (3.47, 14.37)

5.46 (2.59, 11.49)2.97 (1.42, 6.22)

4.91 (0.25, 95.57)

2.95 (1.13, 7.72)

2.82 (1.75, 4.55)

2.26 (1.03, 4.95)

2.13 (1.31, 3.46)

3.23 (1.72, 6.10)

3.69 (2.73, 4.98)

16.35 (2.24, 119.53)

2.63 (1.10, 6.32)

0.30 (0.04, 2.41)

7.54 (3.48, 16.32)

4.73 (3.26, 6.86)

4.78 (2.48, 9.21)

1.82 (0.30, 11.07)

3.66 (1.78, 7.55)

1.75 (0.49, 6.21)

6.12 (1.81, 20.64)

4.49 (2.18, 9.22)

3.56 (1.87, 6.77)

9.27 (2.74, 31.36)

2.87 (1.71, 4.83)

64.25 (3.92, 1052.26)

2.15 (0.13, 34.64)

5.58 (0.23, 137.89)

5.24 (1.52, 18.07)

5.70 (3.34, 9.74)

9.54 (3.28, 27.77)

4.56 (1.47, 14.08)

3.22 (1.28, 8.08)

4.11 (2.59, 6.54)

6.41 (2.87, 14.31)

3.42 (1.75, 6.69)

3.17 (1.30, 7.73)3.61 (1.46, 8.95)

1.73 (0.82, 3.68)

5.10 (2.18, 11.94)

2.45 (1.53, 3.92)

2.35 (0.96, 5.73)

4.18 (2.09, 8.37)

11.83 (0.72, 194.03)

7.06 (0.43, 115.39)

7.67 (0.37, 161.00)

6.18 (2.08, 18.40)

2.88 (1.27, 6.53)

2.90 (1.30, 6.45)

13.97 (4.35, 44.87)

4.03 (1.40, 11.55)

10.91 (3.30, 36.08)

1.76 (0.95, 3.26)

4.26 (0.53, 34.53)

2.54 (0.35, 18.34)

18.74 (2.53, 138.87)

4.54 (2.23, 9.26)

4.26 (1.82, 9.98)

26.98 (6.62, 109.87)

1.13 (0.35, 3.59)

OR (95% CI)

2.13 (1.15, 3.92)

3.51 (1.00, 12.37)

1.70 (1.02, 2.82)

3.01 (1.55, 5.84)

5.19 (1.49, 18.10)

49.85 (2.29, 1082.74)

1.30 (0.08, 20.99)

4.76 (3.39, 6.69)

10.40 (3.17, 34.13)

6.82 (4.12, 11.29)

1.13 (0.24, 5.23)

2.34 (1.10, 4.98)

3.14 (1.26, 7.78)

2.96 (1.66, 5.30)

5.80 (1.69, 19.89)

1.79

1.021.03

0.97

1.55

1.67

1.581.59

0.15

1.11

2.49

1.47

2.46

1.90

3.31

0.33

1.27

0.30

1.50

2.98

1.83

0.39

1.63

0.72

0.77

1.64

1.87

0.77

2.32

0.17

0.17

0.13

0.75

2.26

0.95

0.87

1.18

2.56

1.43

1.79

1.241.21

1.55

1.32

2.53

1.24

1.72

0.17

0.17

0.15

0.92

1.39

1.44

0.82

0.97

0.79

1.97

0.30

0.33

0.32

1.66

1.32

0.61

0.83

Weight

1.98

0.73

2.38

1.81

0.74

0.14

0.17

3.12

0.80

2.39

0.52

1.55

1.21

2.09

0.75

6.50 (3.33, 12.68)

4.17 (1.50, 11.57)6.86 (2.50, 18.83)

3.86 (1.35, 11.03)

5.48 (2.57, 11.67)

7.06 (3.47, 14.37)

5.46 (2.59, 11.49)2.97 (1.42, 6.22)

4.91 (0.25, 95.57)

2.95 (1.13, 7.72)

2.82 (1.75, 4.55)

2.26 (1.03, 4.95)

2.13 (1.31, 3.46)

3.23 (1.72, 6.10)

3.69 (2.73, 4.98)

16.35 (2.24, 119.53)

2.63 (1.10, 6.32)

0.30 (0.04, 2.41)

7.54 (3.48, 16.32)

4.73 (3.26, 6.86)

4.78 (2.48, 9.21)

1.82 (0.30, 11.07)

3.66 (1.78, 7.55)

1.75 (0.49, 6.21)

6.12 (1.81, 20.64)

4.49 (2.18, 9.22)

3.56 (1.87, 6.77)

9.27 (2.74, 31.36)

2.87 (1.71, 4.83)

64.25 (3.92, 1052.26)

2.15 (0.13, 34.64)

5.58 (0.23, 137.89)

5.24 (1.52, 18.07)

5.70 (3.34, 9.74)

9.54 (3.28, 27.77)

4.56 (1.47, 14.08)

3.22 (1.28, 8.08)

4.11 (2.59, 6.54)

6.41 (2.87, 14.31)

3.42 (1.75, 6.69)

3.17 (1.30, 7.73)3.61 (1.46, 8.95)

1.73 (0.82, 3.68)

5.10 (2.18, 11.94)

2.45 (1.53, 3.92)

2.35 (0.96, 5.73)

4.18 (2.09, 8.37)

11.83 (0.72, 194.03)

7.06 (0.43, 115.39)

7.67 (0.37, 161.00)

6.18 (2.08, 18.40)

2.88 (1.27, 6.53)

2.90 (1.30, 6.45)

13.97 (4.35, 44.87)

4.03 (1.40, 11.55)

10.91 (3.30, 36.08)

1.76 (0.95, 3.26)

4.26 (0.53, 34.53)

2.54 (0.35, 18.34)

18.74 (2.53, 138.87)

4.54 (2.23, 9.26)

4.26 (1.82, 9.98)

26.98 (6.62, 109.87)

1.13 (0.35, 3.59)

OR (95% CI)

2.13 (1.15, 3.92)

3.51 (1.00, 12.37)

1.70 (1.02, 2.82)

3.01 (1.55, 5.84)

5.19 (1.49, 18.10)

49.85 (2.29, 1082.74)

1.30 (0.08, 20.99)

4.76 (3.39, 6.69)

10.40 (3.17, 34.13)

6.82 (4.12, 11.29)

1.13 (0.24, 5.23)

2.34 (1.10, 4.98)

3.14 (1.26, 7.78)

2.96 (1.66, 5.30)

5.80 (1.69, 19.89)

1.79

1.021.03

0.97

1.55

1.67

1.581.59

0.15

1.11

2.49

1.47

2.46

1.90

3.31

0.33

1.27

0.30

1.50

2.98

1.83

0.39

1.63

0.72

0.77

1.64

1.87

0.77

2.32

0.17

0.17

0.13

0.75

2.26

0.95

0.87

1.18

2.56

1.43

1.79

1.241.21

1.55

1.32

2.53

1.24

1.72

0.17

0.17

0.15

0.92

1.39

1.44

0.82

0.97

0.79

1.97

0.30

0.33

0.32

1.66

1.32

0.61

0.83

Weight, %

1.98

0.73

2.38

1.81

0.74

0.14

0.17

3.12

0.80

2.39

0.52

1.55

1.21

2.09

0.75

1.05 1 5 10 50

Crohn’s disease

Odds ratio (95% CI)

3.89 (3.58, 4.24)

Supplementary Figure 5. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Ulcerative colitis. All studies..

Random effect

Fixed effect

Annese V (2005)Esters N (2004)

Giachino D (2004)

Weersma RK (2009)

Brant SR (2007)

Helio T (2003)


Zaahl MG (2005)

Hugot JP (2001)

de Ridder L (2007)

Bianchi V (2007)

Ozen SC (2006)

Ferraris A (2006)

Ince AT (2008)

Cucchiara S (2007)

Karban A (2004)

Crawford NPS (2007)

Braat H (2005)

Russel RK (2005)Economou M (2007)

Arnot IDR (2004)

Jess T (2005)

Cuthbert AP (2002)

Rigoli L (2008)

Ernst A (2007)

Gearry RB (2007)


Buning C (2005)

Gazouli M (2004)

Derakhshan F (2008)

Protic MB (2007)

Cavanaugh JA (2003)

Study

1.10 (0.90, 1.34)

0.97 (0.54, 1.77)1.39 (0.75, 2.54)

1.93 (1.02, 3.67)

1.00 (0.77, 1.29)

1.54 (0.75, 3.16)

0.82 (0.23, 2.98)

0.75 (0.40, 1.41)

0.47 (0.06, 3.96)

0.80 (0.31, 2.07)

3.52 (1.42, 8.74)

0.70 (0.27, 1.85)

OR (95% CI)

0.88 (0.22, 3.57)

2.06 (0.74, 5.78)

0.51 (0.13, 1.95)

1.18 (0.64, 2.20)

2.21 (0.55, 8.97)

2.29 (0.63, 8.31)

2.01 (0.97, 4.16)

0.77 (0.27, 2.22)1.26 (0.38, 4.13)

0.46 (0.23, 0.95)

0.11 (0.01, 2.05)

1.04 (0.60, 1.79)

0.91 (0.17, 4.80)

1.16 (0.75, 1.81)

1.51 (0.80, 2.84)

0.78 (0.23, 2.60)

1.19 (0.47, 2.99)

7.52 (1.66, 34.09)

0.25 (0.03, 2.22)

0.09 (0.02, 0.39)

0.13 (0.01, 2.18)

5.085.01

4.77

7.95

4.24

1.95

4.86

0.82

3.04

3.21

2.97

Weight

1.70

2.71

1.81

4.91

1.70

1.94

4.19

2.622.19

4.29

0.45

5.50

1.28

6.36

4.82

2.14

3.14

1.50

0.77

1.59

0.49

0.97 (0.54, 1.77)1.39 (0.75, 2.54)

1.93 (1.02, 3.67)

1.00 (0.77, 1.29)

1.54 (0.75, 3.16)

0.82 (0.23, 2.98)

0.75 (0.40, 1.41)

0.47 (0.06, 3.96)

0.80 (0.31, 2.07)

3.52 (1.42, 8.74)

0.70 (0.27, 1.85)

0.88 (0.22, 3.57)

2.06 (0.74, 5.78)

0.51 (0.13, 1.95)

1.18 (0.64, 2.20)

2.21 (0.55, 8.97)

2.29 (0.63, 8.31)

2.01 (0.97, 4.16)

0.77 (0.27, 2.22)1.26 (0.38, 4.13)

0.46 (0.23, 0.95)

0.11 (0.01, 2.05)

1.04 (0.60, 1.79)

0.91 (0.17, 4.80)

1.16 (0.75, 1.81)

1.51 (0.80, 2.84)

0.78 (0.23, 2.60)

1.19 (0.47, 2.99)

7.52 (1.66, 34.09)

0.25 (0.03, 2.22)

0.09 (0.02, 0.39)

0.13 (0.01, 2.18)

5.085.01

4.77

7.95

4.24

1.95

4.86

0.82

3.04

3.21

2.97

1.70

2.71

1.81

4.91

1.70

1.94

4.19

2.622.19

4.29

0.45

5.50

1.28

6.36

4.82

2.14

3.14

1.50

0.77

1.59

0.49

1.05 1 5 10 50

Ulcerative colitis

Odds ratio (95% CI)

1.06 (0.93, 1.20)

Supplementary Figure 6. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Ulcerative colitis. All studies.


Random effect

Fixed effect

Gearry RB (2007)

Russel RK (2005)


Rigoli L (2008)

Braat H (2005)

Cuthbert AP (2002)

Arnot IDR (2004)

Ernst A (2007)

Crawford NPS (2007)

Economou M (2007)

de Ridder L (2007)

Annese V (2005)

Cucchiara S (2007)

Gazouli M (2004)

Helio T (2003)

Esters N (2004)


Giachino D (2004)

Weersma RK (2009)

Brant SR (2007)

Buning C (2005)

Derakhshan F (2008)Ozen SC (2006)

Cavanaugh JA (2003)

Ferraris A (2006)Ince AT (2008)

Karban A (2004)

Protic MB (2007)

Hugot JP (2001)Jess T (2005)

Bianchi V (2007)

Zaahl MG (2005)

Study

1.10 (0.87, 1.39)

0.94 (0.34, 2.59)

(Excluded)

0.91 (0.44, 1.86)

1.02 (0.31, 3.40)

0.41 (0.17, 0.97)

3.08 (0.90, 10.49)

7.50 (0.96, 58.85)

0.79 (0.35, 1.80)

1.22 (0.30, 4.96)

0.82 (0.43, 1.59)

0.19 (0.01, 3.10)

0.73 (0.33, 1.58)

1.47 (0.72, 2.99)

4.31 (1.80, 10.33)

(Excluded)

1.77 (0.65, 4.85)

0.58 (0.02, 14.49)

1.95 (0.56, 6.82)

1.00 (0.67, 1.50)

2.00 (0.63, 6.38)

1.30 (0.35, 4.90)

OR (95% CI)

1.51 (0.25, 9.12)0.88 (0.12, 6.32)

0.68 (0.04, 11.84)

0.44 (0.05, 3.95)0.69 (0.06, 7.67)

0.62 (0.13, 3.01)

(Excluded)

0.13 (0.01, 2.69)0.20 (0.01, 4.22)

1.80 (0.36, 8.99)

0.94 (0.04, 23.42)

4.27

0.00

7.24

3.23

5.54

3.13

1.22

5.98

2.48

8.12

0.67

6.47

7.34

5.45

0.00

4.36

0.52

3.02

13.69

3.46

2.74

Weight, %

1.571.33

0.65

1.070.90

1.98

0.00

0.570.57

1.92

0.52

0.94 (0.34, 2.59)

(Excluded)

0.91 (0.44, 1.86)

1.02 (0.31, 3.40)

0.41 (0.17, 0.97)

3.08 (0.90, 10.49)

7.50 (0.96, 58.85)

0.79 (0.35, 1.80)

1.22 (0.30, 4.96)

0.82 (0.43, 1.59)

0.19 (0.01, 3.10)

0.73 (0.33, 1.58)

1.47 (0.72, 2.99)

4.31 (1.80, 10.33)

(Excluded)

1.77 (0.65, 4.85)

0.58 (0.02, 14.49)

1.95 (0.56, 6.82)

1.00 (0.67, 1.50)

2.00 (0.63, 6.38)

1.30 (0.35, 4.90)

1.51 (0.25, 9.12)0.88 (0.12, 6.32)

0.68 (0.04, 11.84)

0.44 (0.05, 3.95)0.69 (0.06, 7.67)

0.62 (0.13, 3.01)

(Excluded)

0.13 (0.01, 2.69)0.20 (0.01, 4.22)

1.80 (0.36, 8.99)

0.94 (0.04, 23.42)

4.27

0.00

7.24

3.23

5.54

3.13

1.22

5.98

2.48

8.12

0.67

6.47

7.34

5.45

0.00

4.36

0.52

3.02

13.69

3.46

2.74

1.571.33

0.65

1.070.90

1.98

0.00

0.570.57

1.92

0.52

1.05 1 5 10 50

Ulcerative colitis

Odds ratio (95% CI)

1.10 (0.91, 1.33)

Supplementary Figure 7. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Ulcerative colitis. All studies.


Random effect

Fixed effect

Ince AT (2008)

Cuthbert AP (2002)

Radlmayr M (2002)

Ernst A (2007)

Bianchi V (2007)Rigoli L (2008)van der Linde K (2007)

Buning C (2005)

Karban A (2004)

Braat H (2005)

Hugot JP (2001)

Hampe J (2001)


Cucchiara S (2007)

Esters N (2004)Gearry RB (2007)

Ozen SC (2006)

Crawford NPS (2007)

Study Ulcerative colitits

Protic MB (2007)

Helio T (2003)

Zaahl MG (2005)

Cavanaugh JA (2003)

Derakhshan F (2008)Roussomoustakaki M (2003)

de Ridder L (2007)

Weersma RK (2009)

Giachino D (2004)

Jess T (2005)

Russel RK (2005)

Brant SR (2007)

Gazouli M (2004)

Economou M (2007)

Guo QS (2004)

Ferraris A (2006)

Arnot IDR (2004)

Annese V (2005)

1.02 (0.85, 1.24)

0.46 (0.02, 11.31)

0.71 (0.34, 1.51)

1.24 (0.31, 5.03)

0.89 (0.43, 1.84)

2.41 (0.53, 10.88)0.76 (0.15, 3.83)1.18 (0.19, 7.22)

1.09 (0.38, 3.09)

0.36 (0.04, 3.01)

1.06 (0.44, 2.57)

0.48 (0.11, 2.17)

0.69 (0.23, 2.02)

0.66 (0.29, 1.48)

1.72 (0.72, 4.08)

0.47 (0.16, 1.39)1.41 (0.48, 4.20)

(Excluded)

0.98 (0.31, 3.03)

30.76 (1.79, 529.89)

OR (95% CI)

1.84 (0.66, 5.14)

1.07 (0.28, 4.17)

0.68 (0.04, 11.84)

0.20 (0.01, 4.15)0.28 (0.01, 5.91)

0.79 (0.18, 3.45)

1.00 (0.67, 1.50)

0.24 (0.03, 1.90)

0.25 (0.03, 2.25)

0.29 (0.01, 5.59)

1.24 (0.53, 2.89)

0.57 (0.21, 1.56)

1.06 (0.48, 2.32)

4.70 (0.42, 52.22)

2.24 (0.59, 8.44)

2.82 (0.93, 8.56)

3.76 (1.12, 12.63)

0.35

6.05

1.80

6.35

1.561.351.09

3.18

0.79

4.41

1.56

3.01

5.17

4.57

2.962.94

0.00

2.72

0.44

Weight, %

3.30

1.92

0.44

0.390.39

1.63

18.18

0.82

0.73

0.41

4.77

3.45

5.48

0.62

2.00

2.82

2.39

1.02 (0.85, 1.24)

0.46 (0.02, 11.31)

0.71 (0.34, 1.51)

1.24 (0.31, 5.03)

0.89 (0.43, 1.84)

2.41 (0.53, 10.88)0.76 (0.15, 3.83)1.18 (0.19, 7.22)

1.09 (0.38, 3.09)

0.36 (0.04, 3.01)

1.06 (0.44, 2.57)

0.48 (0.11, 2.17)

0.69 (0.23, 2.02)

0.66 (0.29, 1.48)

1.72 (0.72, 4.08)

0.47 (0.16, 1.39)1.41 (0.48, 4.20)

(Excluded)

0.98 (0.31, 3.03)

30.76 (1.79, 529.89)

1.84 (0.66, 5.14)

1.07 (0.28, 4.17)

0.68 (0.04, 11.84)

0.20 (0.01, 4.15)0.28 (0.01, 5.91)

0.79 (0.18, 3.45)

1.00 (0.67, 1.50)

0.24 (0.03, 1.90)

0.25 (0.03, 2.25)

0.29 (0.01, 5.59)

1.24 (0.53, 2.89)

0.57 (0.21, 1.56)

1.06 (0.48, 2.32)

4.70 (0.42, 52.22)

2.24 (0.59, 8.44)

2.82 (0.93, 8.56)

3.76 (1.12, 12.63)

0.35

6.05

1.80

6.35

1.561.351.09

3.18

0.79

4.41

1.56

3.01

5.17

4.57

2.962.94

0.00

2.72

0.44

3.30

1.92

0.44

0.390.39

1.63

18.18

0.82

0.73

0.41

4.77

3.45

5.48

0.62

2.00

2.82

2.39

1.05 1 5 10 50

Odds ratio (95% CI)

1.05 (0.88, 1.25)

Supplementary Figure 8. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. Northern Europeans.

Random effect

Fixed effect

Ernst A (2007)

Riss L (2007)

Weersma RK (2009)


Hampe J (2002)

Vermeire S (2004)

Cuthbert AP (2002)


Ahmad T (2002)

Arnot IDR (2004)

Helio T (2003)

Braat H (2005)

Russel RK (2005)

Study Crohn’s disease

Vind I (2005)

Jess T (2005)

Buhner S (2006)


Esters N (2004)

de Ridder L (2007)

Torkvist L (2006)

2.17 (1.88, 2.49)

2.02 (1.32, 3.09)

OR (95% CI)

1.93 (1.11, 3.36)

1.65 (1.33, 2.04)

1.88 (1.21, 2.92)

2.72 (1.92, 3.84)

2.94 (1.74, 4.96)

2.72 (1.64, 4.50)

2.15 (0.83, 5.55)

2.63 (1.71, 4.04)

1.48 (0.88, 2.51)

1.84 (0.86, 3.93)

2.89 (1.47, 5.65)

1.19 (0.58, 2.43)

0.23 (0.01, 4.59)

3.76 (1.11, 12.80)

3.15 (1.06, 9.32)

1.53 (0.68, 3.45)

2.42 (1.48, 3.97)

2.96 (1.77, 4.93)

6.68 (1.52, 29.31)

7.48

Weight

5.08

15.58

7.22

9.84

5.57

5.87

2.01

7.42

5.53

3.00

3.70

3.35

0.22

1.25

1.57

2.64

6.05

5.75

0.87

2.17 (1.88, 2.49)

2.02 (1.32, 3.09)

OR (95% CI)

1.93 (1.11, 3.36)

1.65 (1.33, 2.04)

1.88 (1.21, 2.92)

2.72 (1.92, 3.84)

2.94 (1.74, 4.96)

2.72 (1.64, 4.50)

2.15 (0.83, 5.55)

2.63 (1.71, 4.04)

1.48 (0.88, 2.51)

1.84 (0.86, 3.93)

2.89 (1.47, 5.65)

1.19 (0.58, 2.43)

0.23 (0.01, 4.59)

3.76 (1.11, 12.80)

3.15 (1.06, 9.32)

1.53 (0.68, 3.45)

2.42 (1.48, 3.97)

2.96 (1.77, 4.93)

6.68 (1.52, 29.31)

7.48

Weight, %

5.08

15.58

7.22

9.84

5.57

5.87

2.01

7.42

5.53

3.00

3.70

3.35

0.22

1.25

1.57

2.64

6.05

5.75

0.87

1.05 1 5 10 50

Odds ratio (95% CI)

2.12 (1.90, 2.37)

Supplementary Figure 9. Detailed meta-analysis of Gly908Arg on the asis of allele frequencies. Crohn’s disease. Northern Europeans.

Random effectt

Fixed effect

Torkvist L (2006)

Arnot IDR (2004)

Weersma RK (2009)


Cuthbert AP (2002)

Hampe J (2002)

Ernst A (2007)

de Ridder L (2007)

Ahmad T (2002)

Vermeire S (2004)

Study


Riss L (2007)

Vind I (2005)

Jess T (2005)


Braat H (2005)

Esters N (2004)

Russel RK (2005)

Buhner S (2006)

Helio T (2003)

2.30 (1.72, 3.08)

12.30 (0.70, 216.21)

7.10 (0.93, 54.19)

2.05 (1.49, 2.82)

OR (95% CI)

1.42 (0.83, 2.45)

6.71 (2.03, 22.14)

5.72 (2.91, 11.25)

1.55 (0.73, 3.29)

1.31 (0.78, 2.22)

2.33 (1.05, 5.18)

2.10 (0.81, 5.42)

9.88 (1.29, 75.93)

0.99 (0.35, 2.81)

4.32 (0.83, 22.66)

2.31 (0.38, 14.24)

3.98 (0.19, 83.06)

1.11 (0.59, 2.09)

3.43 (1.47, 7.97)

11.20 (0.64, 197.01)

2.63 (0.57, 12.19)

7.79 (0.40, 151.18)

0.96

1.79

12.56

Weight

9.75

4.22

8.21

7.41

9.99

6.98

5.72

1.78

5.10

2.54

2.17

0.86

8.65

6.57

0.96

2.88

0.90

2.30 (1.72, 3.08)

12.30 (0.70, 216.21)

7.10 (0.93, 54.19)

2.05 (1.49, 2.82)

OR (95% CI)

1.42 (0.83, 2.45)

6.71 (2.03, 22.14)

5.72 (2.91, 11.25)

1.55 (0.73, 3.29)

1.31 (0.78, 2.22)

2.33 (1.05, 5.18)

2.10 (0.81, 5.42)

9.88 (1.29, 75.93)

0.99 (0.35, 2.81)

4.32 (0.83, 22.66)

2.31 (0.38, 14.24)

3.98 (0.19, 83.06)

1.11 (0.59, 2.09)

3.43 (1.47, 7.97)

11.20 (0.64, 197.01)

2.63 (0.57, 12.19)

7.79 (0.40, 151.18)

0.96

1.79

12.56

Weight, %

9.75

4.22

8.21

7.41

9.99

6.98

5.72

1.78

5.10

2.54

2.17

0.86

8.65

6.57

0.96

2.88

0.90

1.05 1 5 10 50

Crohn’s disease

Odds ratio (95% CI)

2.25 (1.89, 2.68)

Supplementary Figure 10. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. Northern Europeans.

Random effect

Fixed effect

Vind I (2005)

Hampe J (2001)


Vermeire S (2004)

Helio T (2003)


Buhner S (2006)

Murillo L (2002)

Russel RK (2005)

Jess T (2005)

Radlmayr M (2002)

Riss L (2007)

Ernst A (2007)

Braat H (2005)

Study

Cuthbert AP (2002)

Arnot IDR (2004)

Hampe J (2002)

Esters N (2004)

Torkvist L (2006)


de Ridder L (2007)

Ahmad T (2002)

Weersma RK (2009)3.65 (2.98, 4.47)

4.98 (1.55, 16.02)

4.11 (2.59, 6.54)

2.87 (1.71, 4.83)

6.41 (2.87, 14.31)

2.97 (1.42, 6.22)

3.14 (1.26, 7.78)

18.74 (2.53, 138.87)

9.27 (2.74, 31.36)

3.51 (1.00, 12.37)

1.13 (0.24, 5.23)

9.54 (3.28, 27.77)

1.75 (0.78, 3.94)

5.70 (3.34, 9.74)

2.34 (1.10, 4.98)

OR (95% CI)

3.23 (1.72, 6.10)

3.86 (1.35, 11.03)

4.73 (3.26, 6.86)

3.01 (1.55, 5.84)

1.13 (0.35, 3.59)

6.12 (1.81, 20.64)

1.70 (1.02, 2.82)

6.50 (3.33, 12.68)

3.69 (2.73, 4.98)

2.38

7.19

6.56

4.09

4.55

3.47

0.94

2.23

2.12

1.52

2.74

4.04

6.38

4.43

Weight

5.41

2.81

8.31

5.16

2.42

2.24

6.71

5.11

9.203.65 (2.98, 4.47)

4.98 (1.55, 16.02)

4.11 (2.59, 6.54)

2.87 (1.71, 4.83)

6.41 (2.87, 14.31)

2.97 (1.42, 6.22)

3.14 (1.26, 7.78)

18.74 (2.53, 138.87)

9.27 (2.74, 31.36)

3.51 (1.00, 12.37)

1.13 (0.24, 5.23)

9.54 (3.28, 27.77)

1.75 (0.78, 3.94)

5.70 (3.34, 9.74)

2.34 (1.10, 4.98)

OR (95% CI)

3.23 (1.72, 6.10)

3.86 (1.35, 11.03)

4.73 (3.26, 6.86)

3.01 (1.55, 5.84)

1.13 (0.35, 3.59)

6.12 (1.81, 20.64)

1.70 (1.02, 2.82)

6.50 (3.33, 12.68)

3.69 (2.73, 4.98)

2.38

7.19

6.56

4.09

4.55

3.47

0.94

2.23

2.12

1.52

2.74

4.04

6.38

4.43

Weight, %

5.41

2.81

8.31

5.16

2.42

2.24

6.71

5.11

9.20

1.05 1 5 10 50

Crohn’s disease

Odds ratio (95% CI)

3.78 (3.30, 4.32)

Supplementary Figure 11. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. Southern Europeans.

Random effect

Fixed effect

Protic MB (2007)

Karban A (2004)

Ferraris A (2006)

Lakatos PL (2005)

Nagy Z (2005)

Hradsky O (2008)

Vind I (2005)

Giachino D (2004)

Economou M (2007)

Cottone M (2006)

Bianchi V (2007)Nunez C (2004)

Mendoza JL (2003)

Riss L (2007)

Heresbach D (2004)

Study

Vavassori P (2004)

Ferreira AC (2005)

Buning C (2005)

Bene J (2006)

Rodrigo L (2007)

Annese V (2005)

Rigoli L (2008)

Cucchiara S (2007)

Karban A (2005)

Diego CD (2006)

Gazouli M (2004)

Magyari L (2009)

Canto E (2007)


2.34 (1.98, 2.78)

1.50 (0.90, 2.50)

4.13 (1.38, 12.34)

4.51 (1.91, 10.64)

2.55 (1.37, 4.73)

2.30 (1.00, 5.27)

1.48 (0.95, 2.30)

2.04 (0.77, 5.37)

1.56 (0.89, 2.76)

3.85 (1.25, 11.93)

2.98 (1.33, 6.70)

1.79 (0.94, 3.42)1.17 (0.62, 2.20)

3.52 (1.70, 7.26)

2.99 (1.50, 5.97)

2.60 (1.25, 5.43)

1.52 (0.28, 8.37)

OR (95% CI)

3.31 (2.03, 5.38)

2.81 (1.33, 5.92)

1.89 (0.58, 6.10)

0.79 (0.36, 1.72)

2.20 (1.26, 3.85)

4.36 (1.64, 11.55)

3.01 (1.83, 4.95)

4.24 (1.46, 12.30)

2.29 (1.15, 4.58)

11.00 (2.57, 47.14)

1.41 (0.66, 3.03)

6.59 (1.52, 28.55)

2.79 (1.35, 5.76)

5.47

1.99

2.90

4.46

3.04

6.29

2.41

4.92

1.89

3.15

4.244.34

3.66

3.90

3.60

0.92

Weight,%

5.75

3.53

1.77

3.31

5.00

2.39

5.62

2.08

3.88

1.22

3.42

1.20

3.67

2.34 (1.98, 2.78)

1.50 (0.90, 2.50)

4.13 (1.38, 12.34)

4.51 (1.91, 10.64)

2.55 (1.37, 4.73)

2.30 (1.00, 5.27)

1.48 (0.95, 2.30)

2.04 (0.77, 5.37)

1.56 (0.89, 2.76)

3.85 (1.25, 11.93)

2.98 (1.33, 6.70)

1.79 (0.94, 3.42)1.17 (0.62, 2.20)

3.52 (1.70, 7.26)

2.99 (1.50, 5.97)

2.60 (1.25, 5.43)

1.52 (0.28, 8.37)

OR (95% CI)

3.31 (2.03, 5.38)

2.81 (1.33, 5.92)

1.89 (0.58, 6.10)

0.79 (0.36, 1.72)

2.20 (1.26, 3.85)

4.36 (1.64, 11.55)

3.01 (1.83, 4.95)

4.24 (1.46, 12.30)

2.29 (1.15, 4.58)

11.00 (2.57, 47.14)

1.41 (0.66, 3.03)

6.59 (1.52, 28.55)

2.79 (1.35, 5.76)

5.47

1.99

2.90

4.46

3.04

6.29

2.41

4.92

1.89

3.15

4.244.34

3.66

3.90

3.60

0.92

5.75

3.53

1.77

3.31

5.00

2.39

5.62

2.08

3.88

1.22

3.42

1.20

3.67

1.05 1 5 10 50

Odds ratio (95% CI)

Crohn’s disease

2.36 (2.07, 2.68)

Supplementary Figure 12. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Crohn’s disease. Southern Europeans.

Odds ratio (95% CI)

Crohn’s disease

Random effect

Fixed effect

Riss L (2007)

Cottone M (2006)Ferreira AC (2005)

Nunez C (2004)

Rodrigo L (2007)

Bene J (2006)

Vavassori P (2004)

Nagy Z (2005)

Karban A (2004)

Cucchiara S (2007)Hradsky O (2008)

Buning C (2005)

Lakatos PL (2005)

Economou M (2007)

Protic MB (2007)

Study

Karban A (2005)

Diego CD (2006)

Mendoza JL (2003)

Heresbach D (2004)

Rigoli L (2008)


Vind I (2005)

Giachino D (2004)

Bianchi V (2007)

Gazouli M (2004)

Ferraris A (2006)

Annese V (2005)

Canto E (2007)

Magyari L (2009)

3.03 (2.42, 3.80)

1.68 (0.43, 6.58)

4.01 (1.61, 9.99)2.19 (0.90, 5.33)

5.19 (1.49, 18.10)

1.20 (0.24, 5.99)

OR (95% CI)

6.28 (0.78, 50.38)

2.66 (0.97, 7.31)

1.95 (0.43, 8.86)

7.00 (3.12, 15.69)

2.97 (1.63, 5.42)2.82 (1.55, 5.12)

2.58 (0.85, 7.77)

1.76 (0.77, 4.02)

0.84 (0.39, 1.79)

20.60 (1.22, 347.57)

5.76 (2.59, 12.81)

2.63 (0.83, 8.35)

4.64 (1.62, 13.25)

2.37 (0.68, 8.28)

1.03 (0.43, 2.50)

4.15 (0.92, 18.78)

3.69 (0.72, 18.80)

3.17 (1.15, 8.76)

4.79 (1.37, 16.71)

4.55 (1.97, 10.51)

6.89 (2.33, 20.32)

2.85 (1.46, 5.56)

5.83 (0.32, 106.57)

8.20 (1.83, 36.73)2.28

4.224.38

2.64

1.72

Weight

1.08

3.65

1.92

4.97

6.936.99

3.21

4.83

5.36

0.61

5.04

2.99

3.46

2.63

4.42

1.93

1.69

3.63

2.64

4.75

3.30

6.20

0.58

1.95

3.03 (2.42, 3.80)

1.68 (0.43, 6.58)

4.01 (1.61, 9.99)2.19 (0.90, 5.33)

5.19 (1.49, 18.10)

1.20 (0.24, 5.99)

OR (95% CI)

6.28 (0.78, 50.38)

2.66 (0.97, 7.31)

1.95 (0.43, 8.86)

7.00 (3.12, 15.69)

2.97 (1.63, 5.42)2.82 (1.55, 5.12)

2.58 (0.85, 7.77)

1.76 (0.77, 4.02)

0.84 (0.39, 1.79)

20.60 (1.22, 347.57)

5.76 (2.59, 12.81)

2.63 (0.83, 8.35)

4.64 (1.62, 13.25)

2.37 (0.68, 8.28)

1.03 (0.43, 2.50)

4.15 (0.92, 18.78)

3.69 (0.72, 18.80)

3.17 (1.15, 8.76)

4.79 (1.37, 16.71)

4.55 (1.97, 10.51)

6.89 (2.33, 20.32)

2.85 (1.46, 5.56)

5.83 (0.32, 106.57)

8.20 (1.83, 36.73)2.28

4.224.38

2.64

1.72

Weight,%

1.08

3.65

1.92

4.97

6.936.99

3.21

4.83

5.36

0.61

5.04

2.99

3.46

2.63

4.42

1.93

1.69

3.63

2.64

4.75

3.30

6.20

0.58

1.95

1.05 1 5 10 50

3.20 (2.67, 3.83)

Supplementary Figure 13. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. Southern Europeans.

Random effect

Fixed effect


Ferraris A (2006)

Rodrigo L (2007)

Cottone M (2006)

Ferreira AC (2005)

Protic MB (2007)


Mendoza JL (2003)

Lakatos PL (2005)

Karban A (2005)

Cucchiara S (2007)

Rigoli L (2008)

Magyari L (2009)Giachino D (2004)

Diego CD (2006)

Buning C (2005)

Gazouli M (2004)

Nunez C (2004)

Riss L (2007)

Vind I (2005)

Economou M (2007)

Vavassori P (2004)Bianchi V (2007)Bene J (2006)

Karban A (2004)

Hradsky O (2008)

Nagy Z (2005)

Canto E (2007)

Annese V (2005)

Study

Heresbach D (2004)

4.21 (3.61, 4.91)

2.90 (1.30, 6.45)

6.18 (2.08, 18.40)

1.75 (0.49, 6.21)

4.26 (1.82, 9.98)

4.49 (2.18, 9.22)

64.25 (3.92, 1052.26)

1.82 (0.30, 11.07)

3.66 (1.78, 7.55)

4.78 (2.48, 9.21)

3.17 (1.30, 7.73)

4.54 (2.23, 9.26)

OR (95% CI)

3.61 (1.46, 8.95)

5.10 (2.18, 11.94)2.88 (1.27, 6.53)

2.35 (0.96, 5.73)

5.48 (2.57, 11.67)

3.42 (1.75, 6.69)

5.19 (1.49, 18.10)

2.94 (1.16, 7.45)

0.26 (0.01, 4.75)

7.06 (3.47, 14.37)

10.40 (3.17, 34.13)5.80 (1.69, 19.89)5.24 (1.52, 18.07)

3.22 (1.28, 8.08)

4.76 (3.39, 6.69)

4.03 (1.40, 11.55)

4.26 (0.53, 34.53)

13.97 (4.35, 44.87)

2.26 (1.03, 4.95)3.66

1.97

1.45

3.23

4.50

0.30

0.72

4.47

5.42

2.93

4.61

Weight

2.84

3.233.49

2.93

4.10

5.20

1.50

2.70

0.28

4.62

1.651.541.52

2.76

20.22

2.11

0.53

1.72

3.80

4.21 (3.61, 4.91)

2.90 (1.30, 6.45)

6.18 (2.08, 18.40)

1.75 (0.49, 6.21)

4.26 (1.82, 9.98)

4.49 (2.18, 9.22)

64.25 (3.92, 1052.26)

1.82 (0.30, 11.07)

3.66 (1.78, 7.55)

4.78 (2.48, 9.21)

3.17 (1.30, 7.73)

4.54 (2.23, 9.26)

OR (95% CI)

3.61 (1.46, 8.95)

5.10 (2.18, 11.94)2.88 (1.27, 6.53)

2.35 (0.96, 5.73)

5.48 (2.57, 11.67)

3.42 (1.75, 6.69)

5.19 (1.49, 18.10)

2.94 (1.16, 7.45)

0.26 (0.01, 4.75)

7.06 (3.47, 14.37)

10.40 (3.17, 34.13)5.80 (1.69, 19.89)5.24 (1.52, 18.07)

3.22 (1.28, 8.08)

4.76 (3.39, 6.69)

4.03 (1.40, 11.55)

4.26 (0.53, 34.53)

13.97 (4.35, 44.87)

2.26 (1.03, 4.95)3.66

1.97

1.45

3.23

4.50

0.30

0.72

4.47

5.42

2.93

4.61

Weight, %

2.84

3.233.49

2.93

4.10

5.20

1.50

2.70

0.28

4.62

1.651.541.52

2.76

20.22

2.11

0.53

1.72

3.80

1.05 1 5 10 50

Odds ratio (95% CI)

Crohn’s disease

4.45 (3.82, 5.18)

Supplementary Figure 14. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. Adults.

Odds ratio (95% CI)

Crohn’s disease

Random effect

Fixed effect

Annese V (2005)

Karban A (2004)

Diego CD (2006)

Bene J (2006)

Buning C (2005)

Study

Riss L (2007)

Arnot IDR (2004)

Lakatos PL (2005)

de Ridder L (2008)

Brant SR (2007)

Nagy Z (2005)

Torkvist L (2006)

Magyari L (2009)

2.43 (2.03, 2.91)

OR (95% CI)

2.20 (1.26, 3.85)

4.13 (1.38, 12.34)

2.29 (1.15, 4.58)

2.35 (0.71, 7.75)

2.81 (1.33, 5.92)

2.31 (1.50, 3.57)

1.48 (0.88, 2.51)

2.55 (1.37, 4.73)

2.86 (1.69, 4.82)

3.49 (2.08, 5.86)

2.30 (1.00, 5.27)

6.68 (1.52, 29.31)

1.50 (0.63, 3.55)

Weight

10.40

2.71

6.76

2.28

5.84

17.27

11.80

8.46

11.82

12.10

4.72

1.49

4.37

2.43 (2.03, 2.91)

OR (95% CI)

2.20 (1.26, 3.85)

4.13 (1.38, 12.34)

2.29 (1.15, 4.58)

2.35 (0.71, 7.75)

2.81 (1.33, 5.92)

2.31 (1.50, 3.57)

1.48 (0.88, 2.51)

2.55 (1.37, 4.73)

2.86 (1.69, 4.82)

3.49 (2.08, 5.86)

2.30 (1.00, 5.27)

6.68 (1.52, 29.31)

1.50 (0.63, 3.55)

Weight, %

10.40

2.71

6.76

2.28

5.84

17.27

11.80

8.46

11.82

12.10

4.72

1.49

4.37

1.05 1 5 10 50

2.46 (2.06, 2.95)

Supplementary Figure 15. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Crohn’s disease. Adults.

Random effect

Fixed effect

Arnot IDR (2004)

Nagy Z (2005)

Bene J (2006)

Buning C (2005)

Brant SR (2007)

Karban A (2004)

Lakatos PL (2005)

de Ridder L (2008)

Diego CD (2006)

Riss L (2007)

Torkvist L (2006)

Magyari L (2009)

Annese V (2005)

Study

2.59 (1.79, 3.75)

7.10 (0.93, 54.19)

1.95 (0.43, 8.86)

1.80 (0.16, 20.12)

2.58 (0.85, 7.77)

4.06 (1.69, 9.73)

7.00 (3.12, 15.69)

1.76 (0.77, 4.02)

1.37 (0.80, 2.35)

2.63 (0.83, 8.35)

1.21 (0.53, 2.76)

12.30 (0.70, 216.21)

5.78 (0.69, 48.50)

OR (95% CI)

2.85 (1.46, 5.56)

2.90

4.76

2.13

7.57

10.09

11.01

10.75

15.55

7.12

10.73

1.55

2.68

Weight

13.16

2.59 (1.79, 3.75)

7.10 (0.93, 54.19)

1.95 (0.43, 8.86)

1.80 (0.16, 20.12)

2.58 (0.85, 7.77)

4.06 (1.69, 9.73)

7.00 (3.12, 15.69)

1.76 (0.77, 4.02)

1.37 (0.80, 2.35)

2.63 (0.83, 8.35)

1.21 (0.53, 2.76)

12.30 (0.70, 216.21)

5.78 (0.69, 48.50)

OR (95% CI)

2.85 (1.46, 5.56)

2.90

4.76

2.13

7.57

10.09

11.01

10.75

15.55

7.12

10.73

1.55

2.68

Weight, %

13.16

1.05 1 5 10 50

Odds ratio (95% CI)

Crohn’s disease

2.61 (2.02, 3.37)

Supplementary Figure 16. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. Adults.

Odds ratio (95% CI)

Crohn’s disease

Random effect

Fixed effect

de Ridder L (2008)

Bene J (2006)

Lakatos PL (2005)

Karban A (2004)

Annese V (2005)

Nagy Z (2005)

Buning C (2005)

Diego CD (2006)

Arnot IDR (2004)

Study

Magyari L (2009)

Torkvist L (2006)

Riss L (2007)

Brant SR (2007)

3.25 (2.36, 4.49)

1.61 (0.95, 2.71)

4.24 (1.17, 15.37)

4.78 (2.48, 9.21)

3.22 (1.28, 8.08)

13.97 (4.35, 44.87)

4.03 (1.40, 11.55)

5.48 (2.57, 11.67)

2.35 (0.96, 5.73)

3.86 (1.35, 11.03)

OR (95% CI)

4.83 (1.61, 14.47)

1.13 (0.35, 3.59)

2.13 (1.15, 3.92)

2.96 (1.66, 5.30)

11.81

4.60

10.03

7.16

5.29

6.06

8.84

7.41

6.08

Weight

5.75

5.34

10.62

11.02

3.25 (2.36, 4.49)

1.61 (0.95, 2.71)

4.24 (1.17, 15.37)

4.78 (2.48, 9.21)

3.22 (1.28, 8.08)

13.97 (4.35, 44.87)

4.03 (1.40, 11.55)

5.48 (2.57, 11.67)

2.35 (0.96, 5.73)

3.86 (1.35, 11.03)

OR (95% CI)

4.83 (1.61, 14.47)

1.13 (0.35, 3.59)

2.13 (1.15, 3.92)

2.96 (1.66, 5.30)

11.81

4.60

10.03

7.16

5.29

6.06

8.84

7.41

6.08

Weight, %

5.75

5.34

10.62

11.02

1.05 1 5 10 50

3.35 (2.70, 4.16)

Supplementary Figure 17. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. Children.

Odds ratio (95% CI)

Crohn’s disease

Random effect

Fixed effect

Study

Kugathasan S (2005)

Cucchiara S (2007)

Russel RK (2005)

Magyari L (2009)

Bene J (2006)

Tomer G (2003)

de Ridder L (2007)

Ferraris A (2006)

Kugathasan S (2005)

Kugathasan S (2005)

2.17 (1.19, 3.95)

OR (95% CI)

1.26 (0.76, 2.07)

3.01 (1.83, 4.95)

1.19 (0.58, 2.43)

0.64 (0.07, 5.87)

0.64 (0.07, 5.87)

5.47 (1.48, 20.16)

7.89 (4.32, 14.43)

4.51 (1.91, 10.64)

0.44 (0.02, 7.89)

0.53 (0.06, 4.80)

Weight

15.28

15.29

13.78

5.12

5.12

9.47

14.58

12.68

3.47

5.19

2.17 (1.19, 3.95)

OR (95% CI)

1.26 (0.76, 2.07)

3.01 (1.83, 4.95)

1.19 (0.58, 2.43)

0.64 (0.07, 5.87)

0.64 (0.07, 5.87)

5.47 (1.48, 20.16)

7.89 (4.32, 14.43)

4.51 (1.91, 10.64)

0.44 (0.02, 7.89)

0.53 (0.06, 4.80)

Weight, %

15.28

15.29

13.78

5.12

5.12

9.47

14.58

12.68

3.47

5.19

1.05 1 5 10 50

2.41 (1.89, 3.06)

Supplementary Figure 18. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Crohn’s disease. Children.


Odds ratio (95% CI)

Crohn’s disease

Random effect

Fixed effect

Cucchiara S (2007)

Russel RK (2005)

Magyari L (2009)

Bene J (2006)

Study

Tomer G (2003)

Kugathasan S (2005)

Kugathasan S (2005)

Kugathasan S (2005)

de Ridder L (2007)

Ferraris A (2006)

3.52 (2.01, 6.16)

2.97 (1.63, 5.42)

11.20 (0.64, 197.01)

21.90 (2.59, 185.04)

21.90 (2.59, 185.04)

OR (95% CI)

1.96 (0.98, 3.93)

4.27 (2.23, 8.17)

0.96 (0.05, 18.98)

(Excluded)

1.03 (0.41, 2.59)

6.89 (2.33, 20.32)

19.10

5.38

5.38

Weight, %

17.80

18.43

3.08

0.00

14.73

12.80

3.52 (2.01, 6.16)

2.97 (1.63, 5.42)

11.20 (0.64, 197.01)

21.90 (2.59, 185.04)

21.90 (2.59, 185.04)

OR (95% CI)

1.96 (0.98, 3.93)

4.27 (2.23, 8.17)

0.96 (0.05, 18.98)

(Excluded)

1.03 (0.41, 2.59)

6.89 (2.33, 20.32)

19.10

3.30

5.38

5.38

17.80

18.43

0.00

14.73

12.80

1.05 1 5 10 50

3.29 (2.43, 4.43)

Supplementary Figure 19. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. Children.

Odds ratio (95% CI)

Crohn’s disease

Random effect

Fixed effect

Kugathasan S (2005)

Russel RK (2005)

de Ridder L (2007)

Cucchiara S (2007)

Tomer G (2003)

Kugathasan S (2005)

Bene J (2006)

Magyari L (2009)

Study

Ferraris A (2006)

Kugathasan S (2005)

5.06 (3.81, 6.71)

6.82 (4.12, 11.29)

3.51 (1.00, 12.37)

2.35 (1.16, 4.80)

4.54 (2.23, 9.26)

5.46 (2.59, 11.49)

7.06 (0.43, 115.39)

8.44 (2.11, 33.87)

8.44 (2.11, 33.87)

OR (95% CI)

6.18 (2.08, 18.40)

2.15 (0.13, 34.64)

31.63

5.07

15.84

15.82

14.50

1.03

4.16

4.16

Weight

6.75

1.04

5.06 (3.81, 6.71)

6.82 (4.12, 11.29)

3.51 (1.00, 12.37)

2.35 (1.16, 4.80)

4.54 (2.23, 9.26)

5.46 (2.59, 11.49)

7.06 (0.43, 115.39)

8.44 (2.11, 33.87)

8.44 (2.11, 33.87)

OR (95% CI)

6.18 (2.08, 18.40)

2.15 (0.13, 34.64)

31.63

5.07

15.84

15.82

14.50

1.03

4.16

4.16

Weight, %

6.75

1.04

1.05 1 5 10 50

5.05 (3.80, 6.69)

Esters N (2004)

Hugot JP (2001)

Sugimura K (2003)

Vermeire S (2004)

Annese V (2005)

Helio T (2003)

Study

Tukel T (2004)

Zhou Z (2002)

Jess T (2005)

Tukel T (2004)

Vermeire S (2002)

2. 18 (1.59, 2.97)

1.19 (0.86, 1.63)

3.06 (1.47, 6.39)

1.73 (1.10, 2.73)

2.94 (1.74, 4.96)

2.92 (1.60, 5.32)

1.80 (0.49, 6.60)

6.71 (1.04, 43.16)

1.32 (0.61, 2.88)

3.76 (1.11, 12.80)

1.80 (0.63, 5.11)

3.71 (1.49, 9.24)

14.94

7.90

12.31

11.09

9.82

3.56

%

1.92

7.39

3.91

4.98

6.02

1.19 (0.86, 1.63)

3.06 (1.47, 6.39)

1.73 (1.10, 2.73)

2.94 (1.74, 4.96)

2.92 (1.60, 5.32)

1.80 (0.49, 6.60)

6.71 (1.04, 43.16)

OR (95% CI)

1.32 (0.61, 2.88)

3.76 (1.11, 12.80)

1.80 (0.63, 5.11)

3.71 (1.49, 9.24)

14.94

7.90

12.31

11.09

9.82

3.56

1.92

Weight,

7.39

3.91

4.98

6.02

1.05 1 5 10

Crohn’s disease

Supplementary Figure 20. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. Familial cases.

1.92 (1.59, 2.31)

Random effect

Fixed effect

Odds ratio (95% CI)

Sugimura K (2003)Zhou Z (2002)

Tukel T (2004)

Helio T (2003)

Study

Hugot JP (2001)

Vermeire S (2002)

Tukel T (2004)

Jess T (2005)

Esters N (2004)

Vermeire S (2004)Annese V (2005)

2.47 (1.86, 3.28)

1.58 (0.95, 2.63)2.53 (1.30, 4.91)

OR (95% CI)

7.52 (1.90, 29.85)

19.69 (0.80, 486.97)

6.49 (1.57, 26.82)

7.75 (0.98, 61.23)

3.19 (1.55, 6.58)

2.31 (0.38, 14.24)

1.87 (1.12, 3.10)

2.10 (0.81, 5.42)2.75 (1.31, 5.76)

18.2812.26

Weight,

3.35

0.65

%

3.17

1.53

10.67

1.97

18.35

6.6510.27

1.58 (0.95, 2.63)2.53 (1.30, 4.91)

7.52 (1.90, 29.85)6.49 (1.57, 26.82)

7.75 (0.98, 61.23)

3.19 (1.55, 6.58)

2.31 (0.38, 14.24)

1.87 (1.12, 3.10)

2.10 (0.81, 5.42)2.75 (1.31, 5.76)

18.2812.26

3.35

0.65

3.17

1.53

10.67

1.97

18.35

6.6510.27

1.05 1 5 10 50

Crohn’s disease

Supplementary Figure 21. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Crohn’s disease. Familial cases.

2.41 (1.88, 3.09)

Random effect

Fixed effect

Odds ratio (95% CI)

Hugot JP (2001)Helio T (2003)

Tukel T (2004)

Vermeire S (2002)

Ogura Y (2001)

Zhou Z (2002)Vermeire S (2004)

Sugimura K (2003)

Jess T (2005)

Esters N (2004)

Annese V (2005)

Tukel T (2004)

Study

4.17 (2.64, 6.60)

6.86 (2.50, 18.83)7.20 (2.91, 17.81)

6.06 (2.89, 12.72)

OR (95% CI)

11.95 (1.56, 91.56)

2.13 (1.31, 3.46)

2.21 (0.98, 4.97)6.41 (2.87, 14.31)

3.56 (1.87, 6.77)

1.13 (0.24, 5.23)

1.64 (1.10, 2.45)

14.97 (4.53, 49.43)

49.85 (2.29, 1082.74)

6.997.51

8.36

Weight, %

3.35

9.62

8.008.04

8.86

4.78

9.97

6.12

1.77

6.86 (2.50, 18.83)7.20 (2.91, 17.81)

6.06 (2.89, 12.72)

11.95 (1.56, 91.56)

2.13 (1.31, 3.46)

2.21 (0.98, 4.97)6.41 (2.87, 14.31)

3.56 (1.87, 6.77)

1.13 (0.24, 5.23)

1.64 (1.10, 2.45)

14.97 (4.53, 49.43)

49.85 (2.29, 1082.74)

6.997.51

8.36

3.35

9.62

8.008.04

8.86

4.78

9.97

6.12

1.77

1.05 1 5 10

Supplementary Figure 22. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. Familial cases.

Crohn’s disease

3.28 (2.65, 4.05)

Random effect

Fixed effect

Odds ratio (95% CI)

Cottone M (2006)

Vermeire S (2002)

Cuthbert AP (2002)

Esters N (2004)

Buhner S (2006)

Zhou Z (2002)

Tukel T (2004)

Study

Annese V (2005)

Helio T (2003)

Kugathasan S (2005)

1.87 (1.35, 2.59)

2.98 (1.33, 6.70)

3.16 (1.29, 7.72)

2.72 (1.64, 4.50)

1.12 (0.78, 1.61)

3.26 (1.37, 7.74)

1.02 (0.49, 2.14)

2.55 (0.89, 7.30)

1.54 (0.79, 2.99)

1.82 (0.81, 4.10)

0.44 (0.02, 7.89)

8.33

7.30

13.58

16.89

7.62

9.36

5.79

%

10.50

8.28

0.99

2.98 (1.33, 6.70)

3.16 (1.29, 7.72)

2.72 (1.64, 4.50)

1.12 (0.78, 1.61)

3.15 (1.06, 9.32)

1.02 (0.49, 2.14)

2.55 (0.89, 7.30)

OR (95% CI)

1.54 (0.79, 2.99)

1.82 (0.81, 4.10)

0.44 (0.02, 7.89)

8.33

7.30

13.58

16.89

7.62

9.36

5.79

Weight,

10.50

8.28

0.99

1.05 1 5 10

Crohn’s disease

Supplementary Figure 23. Detailed meta-analysis of Arg702Trp on the basis of allele frequencies. Crohn’s disease. Sporadic cases.

Random effect

Fixed effect 1.74 (1.41, 2.14)

Odds ratio (95% CI)

Esters N (2004)

Zhou Z (2002)

Helio T (2003)

Cuthbert AP (2002)

Annese V (2005)

Buhner S (2006)

Tukel T (2004)

Cottone M (2006)

Study

Vermeire S (2002)

Kugathasan S (2005)

2.28 (1.43, 3.62)

1.21 (0.72, 2.05)

1.09 (0.56, 2.14)

7.61 (0.36, 158.95)

6.71 (2.03, 22.14)

2.94 (1.42, 6.10)

OR (95% CI)

1.59 (0.58, 4.35)

4.01 (1.61, 9.99)

7.71 (1.00, 59.25)

0.96 (0.05, 18.98)

16.42

14.13

1.75

7.92

13.24

Weight,

8.08

9.74

10.77

%

3.55

1.81

1.21 (0.72, 2.05)

1.09 (0.56, 2.14)

7.61 (0.36, 158.95)

6.71 (2.03, 22.14)

2.94 (1.42, 6.10)

2.63 (0.57, 12.19)

1.59 (0.58, 4.35)

4.01 (1.61, 9.99)

7.71 (1.00, 59.25)

0.96 (0.05, 18.98)

16.42

14.13

1.75

7.92

13.24

8.08

9.74

10.77

3.55

1.81

1.05 1 5 10

Supplementary Figure 24. Detailed meta-analysis of Gly908Arg on the basis of allele frequencies. Crohn’s disease. Sporadic cases.

Crohn’s disease

Random effect

Fixed effect 2.11 (1.59, 2.80)

Odds ratio (95% CI)

Annese V (2005)

Buhner S (2006)

Hampe J (2001)

Study

Cottone M (2006)

Cuthbert AP (2002)

Tukel T (2004)

Vermeire S (2002)

Zhou Z (2002)

Esters N (2004)

Helio T (2003)

Kugathasan S (2005)

3.41 (2.24, 5.20)

13.01 (3.92, 43.20)

4.11 (2.59, 6.54)

4.26 (1.82, 9.98)

3.23 (1.72, 6.10)

1.87 (0.60, 5.80)

18.96 (2.56, 140.25)

1.48 (0.67, 3.25)

1.85 (1.12, 3.06)

2.16 (0.95, 4.92)

7.06 (0.43, 115.39)

OR (95% CI)

7.07

5.71

13.04

%

9.64

11.55

7.51

3.61

10.18

12.68

9.89

2.09

Weight,

13.01 (3.92, 43.20)

18.74 (2.53, 138.9)

4.11 (2.59, 6.54)

4.26 (1.82, 9.98)

3.23 (1.72, 6.10)

1.87 (0.60, 5.80)

18.96 (2.56, 140.25)

1.48 (0.67, 3.25)

1.85 (1.12, 3.06)

2.16 (0.95, 4.92)

7.06 (0.43, 115.39)

7.07

5.71

13.04

9.64

11.55

7.51

3.61

10.18

12.68

9.89

2.09

1.05 1 5 10 50

Crohn’s disease

Supplementary Figure 25. Detailed meta-analysis of Leu1007fsincC on the basis of allele frequencies. Crohn’s disease. Sporadic cases

Random effect

Fixed effect 3.49 (2.77, 4.40)

Odds ratio (95% CI)

Supplementary Figure 26. Detailed meta-analysis of Arg702Trp heterozygotes versus non-carriers. Crohn’s disease. All studies.

Random effect

Fixed effect

Hradsky O (2008)

Cuthbert AP (2002)

de Ridder L (2007)

Crawford NPS (2007)

Magyari L (2009)

Ferreira AC (2005)

Derakhshan F (2008)

Tukel T (2004)

Economou M (2007)

Cucchiara S (2007)

Vavassori P (2004)

Leung E (2005)

Rigoli L (2008)

Baptista ML (2008)


Jess T (2005)

Buning C (2005)

Ferraris A (2006)

Rodrigo L (2007)

Giachino D (2004)

Ozen SC (2006)

Canto E (2007)

Lakatos PL (2005)


Cavanaugh JA (2003)

Ince AT (2008)


Tukel T (2004)

Ernst A (2007)

Kugathasan S (2005)

Zaahl MG (2005)

Kugathasan S (2005)

Helio T (2003)


Brant SR (2007)

Bianchi V (2007)

Gazouli M (2004)

Study

Buhner S (2006)

Heresbach D (2004)

Vind I (2005)

Bene J (2006)

Braat H (2005)

2.24 (1.89, 2.64)

1.44 (0.91, 2.27)

2.46 (1.44, 4.21)

2.71 (1.55, 4.75)

4.90 (1.45, 16.58)

2.35 (0.91, 6.11)

3.54 (2.09, 5.98)

23.59 (5.02, 110.98)

1.72 (0.70, 4.26)

2.26 (0.66, 7.77)

3.19 (1.86, 5.47)

0.76 (0.11, 5.47)

1.56 (0.81, 3.00)

4.76 (1.76, 12.89)

OR (95% CI)

4.10 (2.14, 7.86)

3.56 (0.41, 31.00)

4.30 (1.20, 15.50)

2.36 (1.07, 5.20)

4.45 (1.84, 10.77)

0.69 (0.30, 1.58)

1.30 (0.71, 2.40)

0.75 (0.13, 4.21)

6.72 (1.51, 29.97)

1.51 (0.78, 2.92)

1.72 (1.09, 2.70)

2.16 (1.36, 3.44)

0.19 (0.02, 1.64)

1.58 (0.68, 3.69)

7.52 (1.07, 52.83)

1.79 (1.13, 2.83)

1.28 (0.74, 2.19)

2.64 (0.72, 9.66)

0.53 (0.06, 4.82)

1.87 (0.87, 4.03)

2.04 (1.26, 3.31)

2.96 (1.70, 5.15)

2.00 (0.99, 4.04)

12.25 (2.82, 53.26)

2.46 (0.79, 7.68)

3.52 (1.52, 8.13)

0.82 (0.28, 2.34)

3.23 (0.67, 15.68)

3.08 (1.44, 6.59)

4.25

3.79

3.67

1.44

2.06

3.85

0.98

2.20

1.41

3.77

0.64

3.19

1.94

Weight

3.21

0.54

1.34

2.60

2.27

2.47

3.39

0.82

1.04

3.16

4.29

4.21

0.55

2.40

0.66

4.24

3.78

1.31

0.52

2.69

4.10

3.70

2.96

1.07

1.60

2.43

1.79

0.95

2.71

1.44 (0.91, 2.27)

2.46 (1.44, 4.21)

2.71 (1.55, 4.75)

4.90 (1.45, 16.58)

2.35 (0.91, 6.11)

3.54 (2.09, 5.98)

23.59 (5.02, 110.98)

1.72 (0.70, 4.26)

2.26 (0.66, 7.77)

3.19 (1.86, 5.47)

0.76 (0.11, 5.47)

1.56 (0.81, 3.00)

4.76 (1.76, 12.89)

OR (95% CI)

4.10 (2.14, 7.86)

3.56 (0.41, 31.00)

4.30 (1.20, 15.50)

2.36 (1.07, 5.20)

4.45 (1.84, 10.77)

0.69 (0.30, 1.58)

1.30 (0.71, 2.40)

0.75 (0.13, 4.21)

6.72 (1.51, 29.97)

1.51 (0.78, 2.92)

1.72 (1.09, 2.70)

2.16 (1.36, 3.44)

0.19 (0.02, 1.64)

1.58 (0.68, 3.69)

7.52 (1.07, 52.83)

1.79 (1.13, 2.83)

1.28 (0.74, 2.19)

2.64 (0.72, 9.66)

0.53 (0.06, 4.82)

1.87 (0.87, 4.03)

2.04 (1.26, 3.31)

2.96 (1.70, 5.15)

2.00 (0.99, 4.04)

12.25 (2.82, 53.26)

2.46 (0.79, 7.68)

3.52 (1.52, 8.13)

0.82 (0.28, 2.34)

3.23 (0.67, 15.68)

3.08 (1.44, 6.59)

4.25

3.79

3.67

1.44

2.06

3.85

0.98

2.20

1.41

3.77

0.64

3.19

1.94

Weight, %

3.21

0.54

1.34

2.60

2.27

2.47

3.39

0.82

1.04

3.16

4.29

4.21

0.55

2.40

0.66

4.24

3.78

1.31

0.52

2.69

4.10

3.70

2.96

1.07

1.60

2.43

1.79

0.95

2.71

1.1 .5 1 2 3 4 5 10 20 50

Odds ratio (95% CI)

Crohn’s disease

2.23 (1.99, 2.49)

Supplementary Figure 27. Detailed meta-analysis of Arg702Trp homozygotes versus non-carriers. Crohn’s disease. All studies.


Random effect Fixed effect

Leung E (2005)

Ince AT (2008)

Vind I (2005)


Lakatos PL (2005)

Bianchi V (2007)

Buhner S (2006)

Zaahl MG (2005)

Crawford NPS (2007)

Helio T (2003)

Kugathasan S (2005)

Derakhshan F (2008)

Tukel T (2004)


Jess T (2005)

de Ridder L (2007)

Bene J (2006)

Giachino D (2004)


Heresbach D (2004)

Rodrigo L (2007)


Braat H (2005)

Magyari L (2009)

Kugathasan S (2005)

Hradsky O (2008)

Ferraris A (2006)Tukel T (2004)

Brant SR (2007)

Cucchiara S (2007)

Buning C (2005)

Cuthbert AP (2002)

Ernst A (2007)

Economou M (2007)

Ozen SC (2006)

Gazouli M (2004)

Ferreira AC (2005)

Baptista ML (2008)

Cavanaugh JA (2003)

Rigoli L (2008)

Vavassori P (2004)

Canto E (2007)


3.18 (1.97, 5.14)

1.06 (0.07, 17.14)

0.38 (0.02, 9.57)

2.28 (0.14, 36.97)

(Excluded)

13.33 (0.80, 223.39)

1.00 (0.06, 16.14)

4.07 (0.21, 80.27)

(Excluded)

1.48 (0.06, 36.65)

(Excluded)

0.94 (0.10, 8.48)

(Excluded)

(Excluded)

8.21 (1.06, 63.93)

(Excluded)

6.59 (0.83, 52.33)

0.72 (0.04, 11.79)

7.09 (0.36, 138.42)

OR (95% CI)

1.55 (0.30, 8.05)

0.55 (0.03, 8.86)

1.22 (0.05, 30.38)

(Excluded)

3.03 (0.38, 24.46)

0.42 (0.04, 4.12)

(Excluded)

4.53 (0.18, 111.49)

4.24 (0.17, 104.98)9.00 (0.36, 223.22)

18.35 (1.01, 333.77)

10.49 (1.22, 90.57)

7.63 (0.36, 160.12)

9.51 (0.53, 169.60)

10.92 (0.52, 228.16)

7.90 (0.40, 155.15)

(Excluded)

(Excluded)

4.78 (0.49, 46.34)

(Excluded)

26.05 (1.48, 458.34)

(Excluded)

2.28 (0.09, 56.45)

1.93 (0.08, 48.27)

2.98

2.23

2.97

0.00

2.90

2.98

2.59

0.00

2.23

0.00

4.77

0.00

0.00

5.47

0.00

5.37

2.95

2.61

Weight

8.49

2.97

2.23

0.00

5.28

4.44

0.00

2.25

2.242.24

2.74

4.96

2.49

2.78

2.50

2.60

0.00

0.00

4.47

0.00

2.80

0.00

2.24

2.22

1.06 (0.07, 17.14)

0.38 (0.02, 9.57)

2.28 (0.14, 36.97)

(Excluded)

13.33 (0.80, 223.39)

1.00 (0.06, 16.14)

4.07 (0.21, 80.27)

(Excluded)

1.48 (0.06, 36.65)

(Excluded)

0.94 (0.10, 8.48)

(Excluded)

(Excluded)

8.21 (1.06, 63.93)

(Excluded)

6.59 (0.83, 52.33)

0.72 (0.04, 11.79)

7.09 (0.36, 138.42)

1.55 (0.30, 8.05)

0.55 (0.03, 8.86)

1.22 (0.05, 30.38)

(Excluded)

3.03 (0.38, 24.46)

0.42 (0.04, 4.12)

(Excluded)

4.53 (0.18, 111.49)

4.24 (0.17, 104.98)9.00 (0.36, 223.22)

18.35 (1.01, 333.77)

10.49 (1.22, 90.57)

7.63 (0.36, 160.12)

9.51 (0.53, 169.60)

10.92 (0.52, 228.16)

7.90 (0.40, 155.15)

(Excluded)

(Excluded)

4.78 (0.49, 46.34)

(Excluded)

26.05 (1.48, 458.34)

(Excluded)

2.28 (0.09, 56.45)

1.93 (0.08, 48.27)

2.98

2.23

2.97

0.00

2.90

2.98

2.59

0.00

2.23

0.00

4.77

0.00

0.00

5.47

0.00

5.37

2.95

2.61

Weight, %

8.49

2.97

2.23

0.00

5.28

4.44

0.00

2.25

2.242.24

2.74

4.96

2.49

2.78

2.50

2.60

0.00

0.00

4.47

0.00

2.80

0.00

2.24

2.22

1.01 .5 1 2 5 10 20 50 100 800

Odds ratio (95% CI)

3.85 (2.50, 5.93)

Supplementary Figure 28. Detailed meta-analysis of Gly908Arg heterozygotes versus non-carriers. Crohn’s disease. All studies.


Random effect

Fixed effect

I


Buning C (2005)

Cuthbert AP (2002)

de Ridder L (2007)

Queiroz DM, (2009)

Rigoli L (2008)

Leung E (2005)

Gazouli M (2004)

Tukel T (2004)

Lakatos PL (2005)

Kugathasan S (2005)Braat H (2005)

Ferreira AC (2005)

Giachino D (2004)


Canto E (2007)

Cucchiara S (2007)

Ferraris A (2006)

Jess T (2005)

Baptista ML (2008)

Ince AT (2008)


Derakhshan F (2008)

Cavanaugh JA (2003)

Buhner S (2006)

Brant SR (2007)

Zaahl MG (2005)

Rodrigo L (2007)

Vavassori P (2004)

Magyari L (2009)

Economou M (2007)

Vind I (2005)


Tukel T (2004)

Hradsky O (2008)

Crawford NPS (2007)

Ozen SC (2006)Bene J (2006)

Heresbach D (2004)

Kugathasan S (2005)


Helio T (2003)

Bianchi V (2007)

Ernst A (2007)

2.34 (1.95, 2.81)

OR (95% CI)

2.07 (1.13, 3.79)

2.63 (0.86, 8.01)

6.32 (1.90, 20.99)

1.40 (0.78, 2.53)

5.45 (1.63, 18.16)

1.13 (0.46, 2.76)

1.93 (0.75, 4.96)

4.89 (2.05, 11.65)

2.70 (1.37, 5.32)

1.84 (0.80, 4.23)

4.50 (2.32, 8.72)0.87 (0.44, 1.70)

1.88 (0.75, 4.76)

3.28 (1.17, 9.14)

1.76 (0.96, 3.22)

6.01 (0.33, 110.83)

2.69 (1.43, 5.06)

5.14 (1.66, 15.89)

2.38 (0.37, 15.11)

1.20 (0.43, 3.37)

0.61 (0.05, 6.92)

2.05 (0.71, 5.91)

5.44 (0.96, 31.01)

3.44 (1.29, 9.16)

2.73 (0.58, 12.85)

4.19 (1.73, 10.14)

0.80 (0.03, 20.02)

1.29 (0.25, 6.50)

2.42 (0.85, 6.84)

5.88 (1.24, 27.75)

0.82 (0.37, 1.82)

3.16 (0.69, 14.45)

10.50 (1.35, 81.62)

4.22 (0.70, 25.63)

2.45 (1.26, 4.74)

8.21 (1.07, 62.71)

0.76 (0.07, 8.60)3.58 (0.41, 31.65)

2.06 (0.57, 7.43)

(Excluded)

7.83 (0.40, 152.36)

4.97 (1.41, 17.49)

1.44 (0.66, 3.12)

Weight, %

5.08

2.17

1.92

5.20

1.91

3.06

2.82

3.18

4.42

3.38

4.564.49

2.89

2.48

5.07

0.38

4.80

2.13

0.90

2.45

0.54

2.36

1.00

2.66

1.24

3.11

0.31

1.14

2.42

1.23

3.62

1.28

0.74

0.94

4.57

0.75

0.540.66

1.73

0.00

0.37

1.78

3.71

2.07 (1.13, 3.79)

2.63 (0.86, 8.01)

6.32 (1.90, 20.99)

1.40 (0.78, 2.53)

5.45 (1.63, 18.16)

1.13 (0.46, 2.76)

1.93 (0.75, 4.96)

4.89 (2.05, 11.65)

2.70 (1.37, 5.32)

1.84 (0.80, 4.23)

4.50 (2.32, 8.72)0.87 (0.44, 1.70)

1.88 (0.75, 4.76)

3.28 (1.17, 9.14)

1.76 (0.96, 3.22)

6.01 (0.33, 110.83)

2.69 (1.43, 5.06)

5.14 (1.66, 15.89)

2.38 (0.37, 15.11)

1.20 (0.43, 3.37)

0.61 (0.05, 6.92)

2.05 (0.71, 5.91)

5.44 (0.96, 31.01)

3.44 (1.29, 9.16)

2.73 (0.58, 12.85)

4.19 (1.73, 10.14)

0.80 (0.03, 20.02)

1.29 (0.25, 6.50)

2.42 (0.85, 6.84)

5.88 (1.24, 27.75)

0.82 (0.37, 1.82)

3.16 (0.69, 14.45)

10.50 (1.35, 81.62)

4.22 (0.70, 25.63)

2.45 (1.26, 4.74)

8.21 (1.07, 62.71)

0.76 (0.07, 8.60)3.58 (0.41, 31.65)

2.06 (0.57, 7.43)

(Excluded)

7.83 (0.40, 152.36)

4.97 (1.41, 17.49)

1.44 (0.66, 3.12)

5.08

2.17

1.92

5.20

1.91

3.06

2.82

3.18

4.42

3.38

4.564.49

2.89

2.48

5.07

0.38

4.80

2.13

0.90

2.45

0.54

2.36

1.00

2.66

1.24

3.11

0.31

1.14

2.42

1.23

3.62

1.28

0.74

0.94

4.57

0.75

0.540.66

1.73

0.00

0.37

1.78

3.71

1.01 .5 1 2 3 5 10 20 50 100 400

Odds ratio (95% CI)

2.33 (2.01, 2.71)

Supplementary Figure 29. Detailed meta-analysis of Gly908Arg homozygotes versus non-carriers. Crohn’s disease. All studies.


Random effect

Fixed effect

Magyari L (2009)

Braat H (2005)

Rodrigo L (2007)


Heresbach D (2004)

Crawford NPS (2007)

Lakatos PL (2005)

Vind I (2005)

Ferraris A (2006)

Queiroz DM, (2009)

Vavassori P (2004)

Giachino D (2004)

Ernst A (2007)

Ince AT (2008)

Zaahl MG (2005)

Gazouli M (2004)

Brant SR (2007)

Kugathasan S (2005)

Buhner S (2006)

Economou M (2007)

Derakhshan F (2008)


Ozen SC (2006)

Ferreira AC (2005)

Tukel T (2004)

Bene J (2006)

Bianchi V (2007)

Kugathasan S (2005)

Hradsky O (2008)


de Ridder L (2007)

Helio T (2003)

Cuthbert AP (2002)

Canto E (2007)

Jess T (2005)

Cavanaugh JA (2003)

Tukel T (2004)

Buning C (2005)

Leung E (2005)

Cucchiara S (2007)

Rigoli L (2008)

Baptista ML (2008)



2.35 (1.16, 4.76)

6.52 (0.31, 137.23)

3.00 (0.16, 56.11)

(Excluded)

0.29 (0.03, 3.25)

1.43 (0.06, 35.53)

0.16 (0.01, 4.00)

(Excluded)

(Excluded)

9.58 (0.49, 187.33)

(Excluded)

2.42 (0.10, 59.89)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

3.21 (0.13, 79.74)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

4.58 (0.18, 113.98)

4.11 (0.17, 101.25)

(Excluded)

3.59 (0.17, 76.52)

(Excluded)

OR (95% CI)

(Excluded)

6.12 (0.68, 55.00)

(Excluded)

1.08 (0.18, 6.52)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

35.31 (1.30, 956.57)

(Excluded)

0.35 (0.01, 8.57)

9.66 (0.46, 202.40)

(Excluded)

(Excluded)

(Excluded)

5.35

5.79

0.00

8.58

4.82

4.82

0.00

0.00

5.62

0.00

4.82

0.00

0.00

0.00

0.00

4.81

0.00

0.00

0.00

0.00

0.00

0.00

4.80

4.83

0.00

5.31

0.00

Weight

0.00

10.30

0.00

15.39

0.00

0.00

0.00

0.00

0.00

4.56

0.00

4.83

5.37

0.00

0.00

0.00

2.35 (1.16, 4.76)

6.52 (0.31, 137.23)

3.00 (0.16, 56.11)

(Excluded)

0.29 (0.03, 3.25)

1.43 (0.06, 35.53)

0.16 (0.01, 4.00)

(Excluded)

(Excluded)

9.58 (0.49, 187.33)

(Excluded)

2.42 (0.10, 59.89)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

3.21 (0.13, 79.74)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

4.58 (0.18, 113.98)

4.11 (0.17, 101.25)

(Excluded)

3.59 (0.17, 76.52)

(Excluded)

OR (95% CI)

(Excluded)

6.12 (0.68, 55.00)

(Excluded)

1.08 (0.18, 6.52)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

35.31 (1.30, 956.57)

(Excluded)

0.35 (0.01, 8.57)

9.66 (0.46, 202.40)

(Excluded)

(Excluded)

(Excluded)

5.35

5.79

0.00

8.58

4.82

4.82

0.00

0.00

5.62

0.00

4.82

0.00

0.00

0.00

0.00

4.81

0.00

0.00

0.00

0.00

0.00

0.00

4.80

4.83

0.00

5.31

0.00

Weigh, %

0.00

10.30

0.00

15.39

0.00

0.00

0.00

0.00

0.00

4.56

0.00

4.83

5.37

0.00

0.00

0.00

1.01 1 5 10 50 100 200

Odds ratio (95% CI)

2.35 (1.26, 4.38)

Supplementary Figure 30. Detailed meta-analysis of Leu1007fsincC heterozygotes versus non-carriers. Crohn’s disease. All studies.

Random effect

Fixed effect

Buning C (2005)

Rodrigo L (2007)

Guo QS (2004)

Jess T (2005)

Braat H (2005)

Crawford NPS (2007)

Brant SR (2007)


Rigoli L (2008)

Murillo L (2002)

Cuthbert AP (2002)

Derakhshan F (2008)

Gazouli M (2004)

Economou M (2007)


Ferreira AC (2005)

Helio T (2003)


Zaahl MG (2005)

Ferraris A (2006)


Heresbach D (2004)

Kugathasan S (2005)

Canto E (2007)

Ogura Y (2001)

Bianchi V (2007)

Cucchiara S (2007)

Hradsky O (2008)

Radlmayr M (2002)

Kugathasan S (2005)


Vavassori P (2004)

Baptista ML (2008)


Leung E (2005)

Vind I (2005)

Buhner S (2006)

Ince AT (2008)

Queiroz DM, (2009)

de Ridder L (2007)

Tukel T (2004)

Ernst A (2007)

Magyari L (2009)

Cavanaugh JA (2003)

Ozen SC (2006)

Hampe J (2001)

Lakatos PL (2005)

Giachino D (2004)

Tukel T (2004)

Bene J (2006)

3.26 (2.80, 3.81)

3.99 (1.78, 8.94)

1.77 (0.49, 6.38)

12.21 (0.72, 205.91)

1.14 (0.24, 5.46)

2.30 (1.06, 4.97)

2.62 (0.97, 7.05)

2.94 (1.61, 5.37)

2.02 (1.26, 3.23)

OR (95% CI)

3.93 (1.55, 9.95)

7.16 (2.04, 25.17)

2.62 (1.35, 5.06)

2.58 (0.35, 18.97)

3.62 (1.77, 7.40)

6.23 (2.86, 13.58)

5.03 (1.43, 17.64)

2.89 (1.33, 6.30)

2.34 (1.07, 5.09)

4.97 (0.25, 97.37)

0.33 (0.04, 2.79)

6.61 (2.19, 19.94)

1.84 (0.30, 11.42)

1.56 (0.68, 3.61)

2.16 (0.13, 35.12)

4.40 (0.54, 36.25)

1.47 (0.87, 2.49)

6.08 (1.76, 21.03)

4.44 (2.13, 9.24)

3.11 (2.11, 4.57)

7.45 (2.44, 22.75)

6.87 (3.99, 11.84)

6.93 (2.03, 23.65)

4.69 (1.50, 14.62)

2.43 (1.37, 4.30)

11.87 (3.55, 39.65)

3.46 (1.34, 8.92)

14.28 (1.88, 108.68)

1.24 (0.08, 20.24)

9.20 (1.49, 56.67)

1.77 (1.00, 3.12)

3.62 (1.70, 7.71)

3.06 (1.67, 5.60)

3.85 (1.56, 9.51)

5.97 (2.68, 13.32)

7.77 (0.37, 164.39)

2.59 (1.56, 4.32)

3.98 (2.02, 7.82)

1.92 (0.79, 4.65)

55.00 (2.41, 1254.33)

3.50 (0.94, 13.01)

2.51

1.23

0.29

0.86

2.67

1.86

3.63

4.61

Weight

2.05

1.27

3.26

0.55

2.95

2.63

1.27

2.63

2.64

0.26

0.49

1.57

0.65

2.39

0.29

0.50

4.17

1.29

2.86

5.37

1.54

4.03

1.32

1.50

3.83

1.36

1.99

0.54

0.29

0.66

3.85

2.75

3.60

2.13

2.53

0.25

4.29

3.16

2.21

0.24

1.17

3.26 (2.80, 3.81)

3.99 (1.78, 8.94)

1.77 (0.49, 6.38)

12.21 (0.72, 205.91)

1.14 (0.24, 5.46)

2.30 (1.06, 4.97)

2.62 (0.97, 7.05)

2.94 (1.61, 5.37)

2.02 (1.26, 3.23)

OR (95% CI)

3.93 (1.55, 9.95)

7.16 (2.04, 25.17)

2.62 (1.35, 5.06)

2.58 (0.35, 18.97)

3.62 (1.77, 7.40)

6.23 (2.86, 13.58)

5.03 (1.43, 17.64)

2.89 (1.33, 6.30)

2.34 (1.07, 5.09)

4.97 (0.25, 97.37)

0.33 (0.04, 2.79)

6.61 (2.19, 19.94)

1.84 (0.30, 11.42)

1.56 (0.68, 3.61)

2.16 (0.13, 35.12)

4.40 (0.54, 36.25)

1.47 (0.87, 2.49)

6.08 (1.76, 21.03)

4.44 (2.13, 9.24)

3.11 (2.11, 4.57)

7.45 (2.44, 22.75)

6.87 (3.99, 11.84)

6.93 (2.03, 23.65)

4.69 (1.50, 14.62)

2.43 (1.37, 4.30)

11.87 (3.55, 39.65)

3.46 (1.34, 8.92)

14.28 (1.88, 108.68)

1.24 (0.08, 20.24)

9.20 (1.49, 56.67)

1.77 (1.00, 3.12)

3.62 (1.70, 7.71)

3.06 (1.67, 5.60)

3.85 (1.56, 9.51)

5.97 (2.68, 13.32)

7.77 (0.37, 164.39)

2.59 (1.56, 4.32)

3.98 (2.02, 7.82)

1.92 (0.79, 4.65)

55.00 (2.41, 1254.33)

3.50 (0.94, 13.01)

2.51

1.23

0.29

0.86

2.67

1.86

3.63

4.61

Weight, %

2.05

1.27

3.26

0.55

2.95

2.63

1.27

2.63

2.64

0.26

0.49

1.57

0.65

2.39

0.29

0.50

4.17

1.29

2.86

5.37

1.54

4.03

1.32

1.50

3.83

1.36

1.99

0.54

0.29

0.66

3.85

2.75

3.60

2.13

2.53

0.25

4.29

3.16

2.21

0.24

1.17

1.01 .5 1 2 3 5 10 20 50 100 400

Odds ratio (95% CI)

3.17 (2.82, 3.57)

Supplementary Figure 31. Detailed meta-analysis of Leu1007fsincC homozygotes versus non-carriers. Crohn’s disease. All studies.

Studies were excluded from meta-analysis if the risk allele/genotype was found neither in cases nor in controls.Odds ratio (95% CI)

Random effect

Fixed effect

Bene J (2006)

Economou M (2007)

Hradsky O (2008)

Baptista ML (2008)

Cuthbert AP (2002)

Canto E (2007)


Bianchi V (2007)

Ferraris A (2006)

Kugathasan S (2005)



Derakhshan F (2008)

Ozen SC (2006)

de Ridder L (2007)

Jess T (2005)

Giachino D (2004)Cavanaugh JA (2003)

Zaahl MG (2005)

Ernst A (2007)

Vind I (2005)

Rodrigo L (2007)Rigoli L (2008)

Buning C (2005)

Brant SR (2007)

Vavassori P (2004)

Leung E (2005)

Ferreira AC (2005)Heresbach D (2004)

Tukel T (2004)

Queiroz DM, (2009)

Helio T (2003)


Hampe J (2001)

Ince AT (2008)

Tukel T (2004)

Magyari L (2009)Radlmayr M (2002)

Cucchiara S (2007)

Murillo L (2002)

Buhner S (2006)

Gazouli M (2004)


Lakatos PL (2005)Ogura Y (2001)


Guo QS (2004)

Braat H (2005)

Crawford NPS (2007)

Kugathasan S (2005)

9.59 (5.83, 15.77)

7.28 (0.38, 138.67)

29.30 (1.66, 518.07)

113.11 (6.88, 1859.45)

(Excluded)

9.50 (0.53, 169.37)

(Excluded)

5.56 (0.28, 109.39)

(Excluded)

(Excluded)

32.41 (1.66, 631.50)

7.53 (0.97, 58.22)

(Excluded)

(Excluded)

OR (95% CI)

1.73 (0.33, 8.99)

(Excluded)

9.22 (0.49, 172.55)15.34 (0.82, 286.26)

(Excluded)

46.93 (2.74, 803.04)

0.83 (0.03, 20.71)

(Excluded)(Excluded)

17.91 (0.98, 326.81)

4.81 (0.20, 118.74)

13.56 (0.77, 239.92)

(Excluded)

18.77 (1.05, 335.00)6.52 (0.36, 117.04)

16.90 (0.80, 356.20)

68.16 (3.22, 1444.37)

8.18 (0.42, 159.19)

(Excluded)

44.78 (2.69, 744.74)

(Excluded)

(Excluded)

12.73 (0.68, 239.21)14.07 (0.75, 265.20)

5.85 (0.24, 144.41)

9.39 (0.48, 183.55)

7.16 (0.39, 131.78)

5.57 (0.26, 117.70)

8.25 (0.45, 149.65)

12.09 (0.71, 204.40)16.92 (0.99, 288.44)

(Excluded)

(Excluded)

1.81 (0.09, 37.87)

1.46 (0.06, 36.21)

(Excluded)

2.85

3.00

3.15

0.00

2.98

0.00

2.79

0.00

0.00

2.80

5.91

0.00

0.00

Weight

9.10

0.00

2.882.89

0.00

3.06

2.40

0.000.00

2.93

2.41

2.99

0.00

2.982.96

2.66

2.65

2.81

0.00

3.13

0.00

0.00

2.872.87

2.41

2.80

2.91

2.65

2.94

3.093.07

0.00

0.00

2.67

2.40

0.00

9.59 (5.83, 15.77)

7.28 (0.38, 138.67)

29.30 (1.66, 518.07)

113.11 (6.88, 1859.45)

(Excluded)

9.50 (0.53, 169.37)

(Excluded)

5.56 (0.28, 109.39)

(Excluded)

(Excluded)

32.41 (1.66, 631.50)

7.53 (0.97, 58.22)

(Excluded)

(Excluded)

OR (95% CI)

1.73 (0.33, 8.99)

(Excluded)

9.22 (0.49, 172.55)15.34 (0.82, 286.26)

(Excluded)

46.93 (2.74, 803.04)

0.83 (0.03, 20.71)


17.91 (0.98, 326.81)

4.81 (0.20, 118.74)

13.56 (0.77, 239.92)

(Excluded)

18.77 (1.05, 335.00)6.52 (0.36, 117.04)

16.90 (0.80, 356.20)

68.16 (3.22, 1444.37)

8.18 (0.42, 159.19)

(Excluded)

44.78 (2.69, 744.74)

(Excluded)

(Excluded)

12.73 (0.68, 239.21)14.07 (0.75, 265.20)

5.85 (0.24, 144.41)

9.39 (0.48, 183.55)

7.16 (0.39, 131.78)

5.57 (0.26, 117.70)

8.25 (0.45, 149.65)

12.09 (0.71, 204.40)16.92 (0.99, 288.44)

(Excluded)

(Excluded)

1.81 (0.09, 37.87)

1.46 (0.06, 36.21)

(Excluded)

2.85

3.00

3.15

0.00

2.98

0.00

2.79

0.00

0.00

2.80

5.91

0.00

0.00

Weight, %

9.10

0.00

2.882.89

0.00

3.06

2.40

0.000.00

2.93

2.41

2.99

0.00

2.982.96

2.66

2.65

2.81

0.00

3.13

0.00

0.00

2.872.87

2.41

2.80

2.91

2.65

2.94

3.093.07

0.00

0.00

2.67

2.40

0.00

1.01 .5 1 10 50 100 200 600

12.17 (7.56, 19.59)

Supplementary Figure 32. Detailed meta-analysis of NOD2/CARD15 simple heterozygtoes versus non-carriers. Crohn’s disease. All studies.

Random effect

Fixed effect

Ferraris A (2006)

Giachino D (2004)


Tukel T (2004)Leung E (2005)

Lakatos PL (2005)

Jess T (2005)

Gazouli M (2004)

Cuthbert AP (2002)

Annese V (2005)Zhou Z (2002)Braat H (2005)

Helio T (2003)

Ernst A (2007)

Derakhshan F (2008)

Rodrigo L (2007)

Hugot JP (2001)Heresbach D (2004)

Arnot IDR (2004)

Vind I (2005)

Ahmad T (2002)Brant SR (2007)

Vavassori P (2004)

Cavanaugh JA (2003)

Buhner S (2006)Torkvist L (2006)

Mendoza JL (2003)


Tukel T (2004)


2.38 (2.03, 2.79)

4.23 (2.19, 8.17)

1.74 (1.05, 2.89)

2.72 (1.32, 5.58)

OR (95% CI)

3.11 (1.76, 5.50)2.23 (1.32, 3.77)

1.97 (1.29, 3.01)

5.36 (1.84, 15.59)

7.00 (3.73, 13.13)

1.87 (1.21, 2.89)

2.42 (1.52, 3.86)1.04 (0.64, 1.67)1.92 (1.18, 3.12)

2.38 (1.33, 4.25)

2.06 (1.45, 2.93)

8.49 (2.92, 24.65)

0.96 (0.49, 1.88)

2.92 (1.63, 5.25)1.93 (1.06, 3.51)

2.06 (1.33, 3.19)

1.78 (0.89, 3.57)

2.40 (1.59, 3.63)2.80 (1.84, 4.28)

3.29 (1.55, 6.96)

1.42 (0.90, 2.23)

6.33 (2.34, 17.13)3.40 (1.35, 8.61)

2.34 (1.24, 4.40)

1.96 (1.34, 2.85)

20.00 (3.48, 115.02)

3.10

3.96

2.81

Weight

3.603.85

4.51

1.66

3.26

4.42

4.234.154.10

3.53

5.00

1.67

3.06

3.503.41

4.43

2.92

4.594.52

2.68

4.32

1.852.04

3.25

4.84

0.74

2.38 (2.03, 2.79)

4.23 (2.19, 8.17)

1.74 (1.05, 2.89)

2.72 (1.32, 5.58)

OR (95% CI)

3.11 (1.76, 5.50)2.23 (1.32, 3.77)

1.97 (1.29, 3.01)

5.36 (1.84, 15.59)

7.00 (3.73, 13.13)

1.87 (1.21, 2.89)

2.42 (1.52, 3.86)1.04 (0.64, 1.67)1.92 (1.18, 3.12)

2.38 (1.33, 4.25)

2.06 (1.45, 2.93)

8.49 (2.92, 24.65)

0.96 (0.49, 1.88)

2.92 (1.63, 5.25)1.93 (1.06, 3.51)

2.06 (1.33, 3.19)

1.78 (0.89, 3.57)

2.40 (1.59, 3.63)2.80 (1.84, 4.28)

3.29 (1.55, 6.96)

1.42 (0.90, 2.23)

6.33 (2.34, 17.13)3.40 (1.35, 8.61)

2.34 (1.24, 4.40)

1.96 (1.34, 2.85)

20.00 (3.48, 115.02)

3.10

3.96

2.81

Weight, %

3.603.85

4.51

1.66

3.26

4.42

4.234.154.10

3.53

5.00

1.67

3.06

3.503.41

4.43

2.92

4.594.52

2.68

4.32

1.852.04

3.25

4.84

0.74

1.01 .5 1 10 50 200 600

Odds ratio (95% CI)

2.25 (2.04, 2.48)

Supplementary Figure 33. Detailed meta-analysis of NOD2/CARD15 compound heterozygtoes versus non-carriers. Crohn’s disease. All studies.

Random effect

Fixed effect

Buhner S (2006)

Cavanaugh JA (2003)

Vind I (2005)


Tukel T (2004)

Ernst A (2007)

Hugot JP (2001)

Ferraris A (2006)

Torkvist L (2006)

Zhou Z (2002)


Arnot IDR (2004)

Cuthbert AP (2002)Lakatos PL (2005)


Helio T (2003)

Heresbach D (2004)

Rodrigo L (2007)

Jess T (2005)

Ahmad T (2002)

Tukel T (2004)

Gazouli M (2004)

Braat H (2005)

Brant SR (2007)

Leung E (2005)

Vavassori P (2004)

Mendoza JL (2003)

Annese V (2005)

Derakhshan F (2008)

8.98 (5.99, 13.47)

4.06 (0.46, 35.75)

90.78 (5.49, 1500.98)

5.12 (0.46, 57.37)

12.50 (0.87, 179.32)

7.10 (1.42, 35.37)

26.80 (1.63, 440.33)

36.91 (2.14, 637.74)

2.67 (0.11, 65.98)

4.88 (0.65, 36.89)

4.95 (1.71, 14.32)

8.77 (1.10, 69.69)

48.66 (2.96, 800.42)25.92 (1.57, 427.92)

16.23 (0.92, 287.11)

5.81 (0.67, 50.37)

2.45 (0.22, 27.14)

15.00 (0.88, 256.96)

(Excluded)

2.50 (0.15, 42.44)

43.12 (5.76, 322.99)

5.11 (1.49, 17.45)

63.16 (3.67, 1087.94)

3.51 (0.80, 15.45)

49.07 (2.89, 834.51)

26.31 (1.53, 453.36)

OR (95% CI)

6.77 (0.35, 132.43)

9.76 (0.55, 173.08)

22.18 (2.97, 165.41)

27.00 (1.35, 540.32)

3.47

2.09

2.81

2.31

6.37

2.10

2.02

1.59

4.01

14.56

3.82

2.092.09

1.99

3.52

2.83

2.03

0.00

2.05

4.05

10.88

2.03

7.48

2.04

2.03

Weight

1.86

1.99

4.07

1.83

8.98 (5.99, 13.47)

4.06 (0.46, 35.75)

90.78 (5.49, 1500.98)

5.12 (0.46, 57.37)

12.50 (0.87, 179.32)

7.10 (1.42, 35.37)

26.80 (1.63, 440.33)

36.91 (2.14, 637.74)

2.67 (0.11, 65.98)

4.88 (0.65, 36.89)

4.95 (1.71, 14.32)

8.77 (1.10, 69.69)

48.66 (2.96, 800.42)25.92 (1.57, 427.92)

16.23 (0.92, 287.11)

5.81 (0.67, 50.37)

2.45 (0.22, 27.14)

15.00 (0.88, 256.96)

(Excluded)

2.50 (0.15, 42.44)

43.12 (5.76, 322.99)

5.11 (1.49, 17.45)

63.16 (3.67, 1087.94)

3.51 (0.80, 15.45)

49.07 (2.89, 834.51)

26.31 (1.53, 453.36)

OR (95% CI)

6.77 (0.35, 132.43)

9.76 (0.55, 173.08)

22.18 (2.97, 165.41)

27.00 (1.35, 540.32)

3.47

2.09

2.81

2.31

6.37

2.10

2.02

1.59

4.01

14.56

3.82

2.092.09

1.99

3.52

2.83

2.03

0.00

2.05

4.05

10.88

2.03

7.48

2.04

2.03

Weight, %

1.86

1.99

4.07

1.83

1.01 .5 1 10 50 200 500

Odds ratio (95% CI)

Giachino D (2004)

12.63 (8.47, 18.83)


Supplementary Figure 34. Detailed meta-analysis of NOD2/CARD15 homozygotes versus non-carriers. Crohn’s disease. All studies.


Random effect

Fixed effect

Hugot JP (2001)

Cuthbert AP (2002)


Torkvist L (2006)

Brant SR (2007)

Helio T (2003)

Zhou Z (2002)

Ferraris A (2006)

Buhner S (2006)

Gazouli M (2004)

Ahmad T (2002)

Tukel T (2004)

Lakatos PL (2005)


Annese V (2005)

Vavassori P (2004)

Braat H (2005)

Leung E (2005)

Cavanaugh JA (2003)

Giachino D (2004)

Heresbach D (2004)

Mendoza JL (2003)

Tukel T (2004)

Derakhshan F (2008)Jess T (2005)


Vind I (2005)

Ernst A (2007)

Arnot IDR (2004)

Rodrigo L (2007)

6.69 (4.13, 10.85)

18.86 (1.14, 312.08)

20.62 (1.21, 350.00)

2.55 (0.93, 6.96)

6.22 (0.32, 121.50)

25.52 (1.43, 456.02)

8.56 (0.44, 166.48)

3.41 (0.44, 26.35)

15.82 (0.84, 297.37)

13.82 (0.78, 244.65)

15.25 (0.77, 302.88)

13.72 (1.67, 112.55)

29.55 (1.50, 581.73)

29.83 (1.81, 490.84)

12.42 (1.62, 95.43)

18.36 (1.06, 319.16)

5.78 (0.75, 44.50)

0.63 (0.06, 6.99)

42.61 (2.50, 727.03)

17.41 (0.98, 307.89)

OR (95% CI)

4.79 (0.59, 39.02)

8.46 (0.47, 152.06)

64.71 (2.21, 1891.71)


6.68 (0.34, 132.00)

1.28 (0.11, 14.34)

59.10 (3.49, 1001.40)

1.30 (0.29, 5.86)

1.28 (0.05, 31.81)

2.76

2.71

14.63

2.48

2.62

2.48

4.90

2.54

2.64

2.45

4.66

2.47

2.77

4.92

2.67

4.91

3.65

2.70

2.64

Weight

4.68

2.61

1.95

0.000.00

2.46

3.63

2.72

8.18

2.14

6.69 (4.13, 10.85)

18.86 (1.14, 312.08)

20.62 (1.21, 350.00)

2.55 (0.93, 6.96)

6.22 (0.32, 121.50)

25.52 (1.43, 456.02)

8.56 (0.44, 166.48)

3.41 (0.44, 26.35)

15.82 (0.84, 297.37)

13.82 (0.78, 244.65)

15.25 (0.77, 302.88)

13.72 (1.67, 112.55)

29.55 (1.50, 581.73)

29.83 (1.81, 490.84)

12.42 (1.62, 95.43)

18.36 (1.06, 319.16)

5.78 (0.75, 44.50)

0.63 (0.06, 6.99)

42.61 (2.50, 727.03)

17.41 (0.98, 307.89)

OR (95% CI)

4.79 (0.59, 39.02)

8.46 (0.47, 152.06)

64.71 (2.21, 1891.71)


6.68 (0.34, 132.00)

1.28 (0.11, 14.34)

59.10 (3.49, 1001.40)

1.30 (0.29, 5.86)

1.28 (0.05, 31.81)

2.76

2.71

14.63

2.48

2.62

2.48

4.90

2.54

2.64

2.45

4.66

2.47

2.77

4.92

2.67

4.91

3.65

2.70

2.64

Weight, %

4.68

2.61

1.95

0.000.00

2.46

3.63

2.72

8.18

2.14

1.01 .5 1 10 50 200 600

Odds ratio (95% CI)

8.08 (5.33, 12.26)

Search in electronic databases (n=1558) PubMed: 760 Embase: 795 Web of Science: 3

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