Supplementary Table 1. Results of Meta-Analysis of Japanese IBD
Supplementary Table 1. Results of meta-analysis of Japanese IBD
Locus/Gene / Allele*[1/2] / Study / Number / RAF / OR (95%CI) / Combined / Heterogeneity
rsID / case / control / case / control / P** / OR (95%CI) / P / I2 statistics (%)
NKX2-3 / CD
rs10883365 / G/A / Arai (2011) / 344 / 243 / 0.44 / 0.38 / 1.16(1.01-1.34) / 9.5E-4 / 1.13 (1.05-1.22) / 0.57 / 0
Yamazaki (2009) / 481 / 470 / 0.47 / 0.41 / 1.15 (1.04-1.27)
Tanaka (2009) / 165 / 393 / 0.40 / 0.38 / 1.05(0.90-1.23)
Total / 990 / 1106
UC
rs10883365 / Arai (2011) / 253 / 243 / 0.48 / 0.38 / 1.28 (1.11-1.48) / 9.0E-6 / 1.24 (1.13-1.36) / 0.55 / 0
Tanaka (2009) / 295 / 393 / 0.46 / 0.38 / 1.21 (1.07-1.37)
Total / 548 / 636
CD
rs888208 / A/G / Arai (2011) / 344 / 243 / 0.58 / 0.53 / 1.08 (0.98-1.20) / 0.005 / 1.08 (1.02-1.14) / 0.93 / 0
Yamazaki (UD) / 372 / 3366 / 0.60 / 0.56 / 1.08 (1.01-1.15)
Total / 716 / 3609
UC
rs888208 / Arai (2011) / 253 / 243 / 0.65 / 0.53 / 1.21 (1.09-1.34) / 0.002 / 1.09 (1.03-1.15) / 0.02 / 80.7
Yamazaki (UD) / 371 / 3366 / 0.58 / 0.56 / 1.05 (0.98-1.12)
Total / 624 / 3609
TNFSF15 / CD
rs3810936 / G/A / Nakagome (2010) / 130 / 163 / 0.73 / 0.63 / 1.15 (1.03-1.29) / 6.5E-14 / 1.23 (1.17-1.30) / 0.33 / 11.0
Kakuta (2006) / 286 / 277 / 0.73 / 0.60 / 1.22 (1.12-1.33)
Yamazaki (2005) / 477 / 334 / 0.73 / 0.57 / 1.27 (1.17-1.30)
Total / 893 / 774
UC
rs3810936 / Nakagome (2010) / 82 / 163 / 0.74 / 0.63 / 1.18 (1.04-1.33) / 0.008 / 1.10 (1.02-1.19) / 0.20 / 37.3
Kakuta (2006) / 263 / 277 / 0.64 / 0.60 / 1.07 (0.97-1.17)
Total / 345 / 440
CD
rs6478108 / A/G / Kakuta (2006) / 286 / 277 / 0.19 / 0.26 / 0.73 (0.59-0.91) / 0.919 / 0.97 (0.55-1.71) / 0 / 95.8
Yamazaki (2005) / 479 / 344 / 0.75 / 0.59 / 1.27 (1.18-1.36)
Total / 765 / 621
CD
rs7848647 / G/A / Kakuta (2006) / 286 / 277 / 0.13 / 0.19 / 0.66 (0.51-0.87) / 0.819 / 0.93 (0.48-1.79) / 0 / 95.5
Yamazaki (2005) / 468 / 345 / 0.75 / 0.59 / 1.26 (1.17-1.35)
Total / 754 / 622
ATG16L1 / CD
rs2241880 / G/A / Nakagome (2010) / 129 / 163 / 0.28 / 0.26 / 1.06 (0.81-1.38) / 0.376 / 0.94 (0.82-1.08) / 0.33 / 0
Yamazaki (2007) / 481 / 437 / 0.24 / 0.26 / 0.90 (0.77-1.06)
Total / 610 / 600
IRGM / CD
rs10065172 / C/T / Nakagome (2010) / 130 / 164 / 0.60 / 0.63 / 0.95 (0.84-1.09) / 0.355 / 0.96 (0.89-1.04) / 0.89 / 0
Prescott (2010) / 484 / 933 / 0.37 / 0.38 / 0.97 (0.87-1.07)
Total / 614 / 1097
10q21 / CD
rs10761659 / G/A / Nakagome(2010) / 129 / 163 / 0.72 / 0.68 / 1.06 (1.00-1.13) / 0.026 / 1.06 (1.01-1.12) / 0.81 / 0
Yamazaki(2009) / 482 / 470 / 0.72 / 0.68 / 1.05 (0.94-1.17)
Total / 611 / 633
IL17 / UC
rs2275913 / A/G / Hayashi (2012) / 202 / 475 / 0.42 / 0.34 / 1.21 (1.05-1.40) / 0.668 / 1.06 (0.82-1.37) / 3E-3 / 88.3
Yamazaki (UD) / 371 / 3366 / 0.37 / 0.40 / 0.93 (0.85-1.03)
Total / 573 / 3841
UC
rs763780 / C/T / Arisawa (2008) / 111 / 247 / 0.08 / 0.14 / 0.59 (0.36-0.97) / 0.488 / 0.85 (0.54-1.34) / 1E-3 / 84.7
Yamazaki (UD) / 371 / 3365 / 0.14 / 0.11 / 1.25 (1.03-1.51)
Arimura (PS) / 403 / 361 / 0.09 / 0.12 / 0.75 (0.56-1.34)
Total / 885 / 3973
TNF / CD
rs1800629 / A/G / Sashio (2002) / 124 / 111 / 0.02 / 0.01 / 2.69 (0.55-13.17) / 0.711 / 1.35 (0.28-6.46) / 0.21 / 35.2
Negoro (1999) / 54 / 575 / 0.01 / 0.02 / 0.53 (0.07-3.93)
Total / 178 / 686
UC
Sashio (2002) / 106 / 111 / 0.08 / 0.01 / 9.42 (2.21-40.13) / 0.716 / 1.92 (0.06-63.75) / 0.03 / 80.1
Negoro (1999) / 54 / 575 / 0.00 / 0.02 / 0.26 (0.02-4.23)
Total / 160 / 686
CD
rs1799964 / C/T / Negoro (1999) / 103 / 575 / 0.24 / 0.16 / 1.52 (1.15-2.00) / 3.0E-4 / 1.31 (1.05-1.63) / 0.15 / 52.8
rs1041981 / C/T / Yamazaki (UD) / 372 / 3366 / 0.22 / 0.19 / 1.21 (1.04-1.39)
Total / 475 / 3941
UC
Negoro (1999) / 76 / 575 / 0.12 / 0.16 / 0.74 (0.47-1.17) / 0.026 / 0.83 (0.71-0.98) / 0.59 / 0
Yamazaki (UD) / 371 / 3366 / 0.16 / 0.19 / 0.85 (0.71-1.01)
Total / 447 / 3941
CD
rs1800630 / A/C / Negoro (1999) / 103 / 575 / 0.22 / 0.14 / 1.56 (1.16-2.10) / 2.0E-4 / 1.34 (1.07-1.67) / 0.17 / 47.6
rs2844482
(proxy)b / A/G / Yamazaki (UD) / 372 / 3362 / 0.20 / 0.16 / 1.23 (1.06-1.44)
Total / 475 / 3937
UC
Negoro (1999) / 76 / 575 / 0.11 / 0.14 / 0.80 (0.50-1.28) / 0.317 / 1.02 (0.73-1.42) / 0.16 / 48.7
Yamazaki (UD) / 280 / 3362 / 0.18 / 0.16 / 1.15 (0.94-1.29)
Total / 356 / 3937
CD
rs1799724 / T/C / Matsuoka (2003) / 76 / 99 / 0.24 / 0.18 / 1.34 (0.89-2.03) / 0.003 / 1.48 (1.19-1.84) / 0.59 / 0
Negoro (1999) / 103 / 575 / 0.27 / 0.18 / 1.53 (1.19-1.98)
Total / 179 / 674
UC
Matsuoka (2003) / 92 / 99 / 0.10 / 0.18 / 0.55 (0.33-0.94) / 0.006 / 0.62 (0.44-0.87) / 0.60 / 0
Negoro (1999) / 76 / 575 / 0.12 / 0.18 / 0.67 (0.43-1.05)
Total / 168 / 674
CD
rs361525 / A/G / Sashio (2002) / 124 / 111 / 0.03 / 0.01 / 3.13 (0.66-14.93) / 0.306 / 1.70 (0.62-4.66) / 0.26 / 21.9
Negoro (1999) / 54 / 575 / 0.02 / 0.02 / 0.93 (0.22-3.87)
Total / 178 / 686
UC
Sashio (2002) / 106 / 111 / 0.01 / 0.01 / 1.57 (0.27-9.31) / 0.776 / 0.83 (0.23-3.00) / 0.36 / 0
Negoro (1999) / 54 / 575 / 0.01 / 0.02 / 0.46 (0.06-3.40)
Total / 160 / 686
PPAR / UC
rs1801282 / G/C / Aoyagi (2010) / 29 / 134 / 0.10 / 0.01 / 6.93 (2.02-23.78) / 0.265 / 1.78 (0.65-4.91) / 0.02 / 73.7
Wang (2008) / 118 / 142 / 0.02 / 0.02 / 0.86 (0.28-2.67)
rs2197423
(proxy)c / G/A / Yamazaki (UD) / 371 / 3366 / 0.04 / 0.03 / 1.23 (0.85-1.79)
Total / 518 / 3642
TYK2 / CD
rs280519 / A/G / Sato (2009) / 83 / 200 / 0.66 / 0.56 / 1.17 (1.02-1.40) / 0.115 / 1.08 (0.95-1.23) † / 0.09 / 65.9
Yamazaki (UD) / 372 / 3366 / 0.56 / 0.55 / 1.02 (0.96-1.10)
Total / 455 / 3566
CTLA4 / CD
rs3087243 / A/G / Machida(2005) / 79 / 200 / 0.27 / 0.31 / 0.89 (0.66-1.20) / 0.678 / 1.02 (0.92-1.15) / 0.32 / 0
rs231735
(proxy)d / T/G / Yamazaki (UD) / 372 / 3366 / 0.28 / 0.27 / 1.05 (0.92-1.15)
Total / 451 / 3566
UC
Machida(2005) / 108 / 200 / 0.27 / 0.31 / 0.88 (0.68-1.15) / 0.534 / 1.04 (0.93-1.15) / 0.19 / 43.1
Yamazaki (UD) / 371 / 3366 / 0.29 / 0.27 / 1.07 (0.95-1.21)
Total / 479 / 3566
ICAM1 / CD
rs5498 / G/A / Matsuzawa (2003) / 79 / 103 / 0.35 / 0.50 / 0.69(0.54-0.89) / 0.280 / 0.83 (0.60-1.16) / 0.01 / 83.5
Yamazaki (UD) / 372 / 3358 / 0.39 / 0.40 / 0.97 (0.88-1.06)
Total / 451 / 3461
UC
Matsuzawa (2003) / 128 / 103 / 0.38 / 0.50 / 0.76 (0.62-0.93) / 0.362 / 0.88 (0.68-1.15) / 0.02 / 82.2
Yamazaki (UD) / 371 / 3358 / 0.40 / 0.40 / 1.00 (0.91-1.09)
Total / 499 / 3461
PTPN11 / CD
rs2301756 / G/A / Narumi (2009) / 83 / 200 / 0.78 / 0.75 / 1.04 (0.94-1.15) / 0.767 / 0.99 (0.94-1.05) † / 0.25 / 24.7
rs10850014
(proxy)e / G/A / Yamazaki(UD) / 372 / 3366 / 0.78 / 0.79 / 0.98 (0.99-1.02)
Total / 455 / 3566
UC
Narumi (2009) / 114 / 200 / 0.85 / 0.75 / 1.13 (1.04-1.22) / 0.297 / 1.06 (0.95-1.18) / 0.01 / 83.5
Yamazaki (UD) / 371 / 3366 / 0.80 / 0.79 / 1.01 (0.97-1.05)
Total / 485 / 3566
CD
rs3741983 / T/C / Narumi (2009) / 83 / 200 / 0.78 / 0.76 / 1.03 (0.94-1.14) / 0.511 / 1.05 (0.96-1.14) † / 0.32 / 0
rs11066322
(proxy)f / A/G / Yamazaki (UD) / 372 / 3366 / 0.78 / 0.80 / 0.99 (0.95-1.03)
Total / 455 / 3566
UC
Narumi (2009) / 114 / 200 / 0.83 / 0.76 / 1.10 (1.02-1.19) / 0.286 / 1.05 (0.96-1.14) / 0.06 / 72.1
Yamazaki (UD) / 371 / 3366 / 0.80 / 0.80 / 1.01 (0.97-1.05)
Total / 485 / 3566
MDR1 / UC
rs1045642 / T/C / Osuga (2006) / 66 / 173 / 0.49 / 0.39 / 1.26 (1.02-1.57) / 0.802 / 1.05 (0.72-1.52) † / 0.02 / 80.7
Arimura (UD) / 90 / 90 / 0.39 / 0.45 / 0.86 (0.68-1.10)
Total / 156 / 263
SFTPD / UC
rs911887 / G/A / Tanaka (2009) / 295 / 393 / 0.67 / 0.75 / 1.33 (1.12-1.57) / 0.260 / 1.16 (0.90-1.49) / 3E-3 / 88.5
Arimura (UD) / 744 / 1127 / 0.29 / 0.31 / 1.03 (0.99-1.08)
Total / 1039 / 1520
SHMT1 / UC
rs1979277 / A/G / Kosaka (2009) / 145 / 120 / 0.20 / 0.15 / 1.35 (0.92-1.98) / 0.401 / 1.12 (0.86-1.48) / 0.22 / 33.3
rs12952556
(proxy)g / C/T / Yamazaki (UD) / 371 / 3366 / 0.08 / 0.08 / 1.01 (0.78-1.30)
Total / 516 / 3486
MIF / UC
rs755622 / C/G / Shiroeda (2010) / 111 / 209 / 0.21 / 0.22 / 2.06 (1.50-2.84) / 0.935 / 1.06 (0.29-3.87) † / 0 / 97.8
Nohara (2004) / 221 / 438 / 0.22 / 0.19 / 0.55 (0.44-0.68)
Total / 332 / 647
TLR9 / UC
rs187084 / C/T / Fuse (2010) / 48 / 47 / 0.66 / 0.47 / 1.40 (1.08-1.82) / 0.201 / 1.19 (0.91-1.54) / 0.05 / 74.9
rs352140 / G/A / Fuse (2010) / 48 / 47 / 0.65 / 0.46 / 1.07 (0.99-1.15)
rs352139 / A/G / Fuse (2010) / 48 / 47 / 0.66 / 0.47
rs352163
(proxy)h / T/C / Yamazaki (UD) / 371 / 3366 / 0.53 / 0.50
Total / 515 / 3507
CD14 / CD
rs2569190 / G/A / Matsuoka (2003) / 76 / 99 / 0.60 / 0.51 / 1.19 (0.98-1.43) / 0.263 / 1.04 (0.97-1.10) / 0.48 / 0
Obana (2002) / 82 / 123 / 0.48 / 0.45 / 1.08 (0.87-1.33)
rs2569188
(proxy)i / C/T / Yamazaki (UD) / 371 / 3344 / 0.46 / 0.46 / 1.01 (0.93-1.09)
Arimura (PS) / 178 / 360 / 0.47 / 0.46 / 1.03 (0.90-1.17)
Total / 707 / 3926
UC
Wang (2007) / 97 / 135 / 0.66 / 0.49 / 1.36 (1.16-1.59) / 0.005 / 1.14 (1.01-1.29) / 2E-3 / 76.5
Matsuoka (2003) / 89 / 99 / 0.59 / 0.51 / 1.17 (0.97-1.40)
Obana (2002) / 101 / 123 / 0.57 / 0.45 / 1.28 (1.07-1.54)
Arimura (PS) / 402 / 360 / 0.48 / 0.46 / 1.05 (0.94-1.16)
Yamazaki (UD) / 369 / 3344 / 0.46 / 0.46 / 0.99 (0.91-1.07)
Total / 1058 / 4061
NFKBIL1 / UC
rs2071592 / T/A / Oomori (2009) / 250 / 303 / 0.66 / 0.57 / 1.17 (1.06-1.28) / 4.5E-9 / 1,14 (1.09-1.19) / 0.54 / 0
rs1041981
(proxy)j / G/T / Yamazaki(UP) / 371 / 3356 / 0.71 / 0.63 / 1.13 (1.08-1.19)
Total / 621 / 3659
UC
rs3219184 / G/A / Oomori (2009) / 250 / 303 / 0.33 / 0.16 / 2.07 (1.66-2.57) / 1.3E-38 / 1.93 (1.75-2.13) / 0.45 / 0
rs2071593
(proxy)k / A/G / Yamazaki(UP) / 371 / 3366 / 0.35 / 0.19 / 1.88 (1.69-2.10)
Total / 621 / 3669
IL18 / CD
rs1946518 / G/T / Takagawa (2005) / 210 / 212 / 0.18 / 0.21 / 0.86 (0.66-1.14) / 0.124 / 0.93 (0.85-1.02) / 0.54 / 0
Yamazaki (UD) / 372 / 3359 / 0.39 / 0.41 / 0.94 (0.86-1.04)
Total / 582 / 3571
UC
Takagawa (2005) / 205 / 212 / 0.17 / 0.21 / 0.83 (0.62-1.09) / 0.157 / 0.94 (0.86-1.03) / 0.33 / 0
Yamazaki (UD) / 371 / 3359 / 0.39 / 0.41 / 0.96 (0.87-1.05)
Total / 576 / 3571
CD
rs549908 / T/G / Tamura (2002) / 134 / 110 / 0.17 / 0.09 / 1.99 (1.20-3.29) / 0.270 / 1.40 (0.77-2.53) / 0.03 / 79.6
rs795467
(proxy)l / A/G / Yamazaki (UD) / 372 / 3366 / 0.12 / 0.11 / 1.08 (0.88-1.32)
Total / 506 / 3476
UC
Tamura (2002) / 110 / 110 / 0.10 / 0.09 / 1.11 (0.61-2.00) / 0.624 / 1.05 (0.86-1.28) / 0.86 / 0
Yamazaki (UD) / 371 / 3366 / 0.12 / 0.11 / 1.04 (0.86-1.28)
Total / 481 / 3476
HLA-B / CD
*4002 / Okada (2011) / 372 / 905 / 0.15 / 0.12 / 1.18 (0.96-1.46) / 0.511 / 1.07 (0.88-1.31) / 0.18 / 44.0
Kinouchi (2003) / 195 / 185 / 0.30 / 0.31 / 0.97 (0.78-1.19)
Total / 567 / 1090
UC
Okada (2011) / 372 / 905 / 0.12 / 0.12 / 0.97 (0.77-1.22) / 0.284 / 0.74 (0.43-1.28) / 0.13 / 86.7
Aizawa (2009) / 318 / 319 / 0.08 / 0.14 / 0.56 (0.40-0.77)
Total / 690 / 1224
CD
*5201 / Okada (2011) / 372 / 905 / 0.08 / 0.14 / 0.54 (0.41-0.71) / 0.010 / 0.64 (0.45-0.90) † / 0.10 / 62.7
Kinouchi (2003) / 195 / 185 / 0.15 / 0.19 / 0.76 (0.45-0.90)
Total / 567 / 1090
UC
Okada (2011) / 372 / 905 / 0.29 / 0.14 / 2.08 (1.77-2.44) / 1.9E-43 / 2.69 (2.24-3.23) / 0.11 / 54.4
Aizawa (2009) / 318 / 319 / 0.29 / 0.10 / 2.88 (2.22-3.75)
Seki(2001) / 64 / 236 / 0.56 / 0.25 / 2.25 (1.81-2.80)
Total / 754 / 1460
HLA-DRB1 / CD
*0405 / Okada(2011) / 372 / 905 / 0.21 / 0.13 / 1.61 (1.34-1.94) / 2.7E-10 / 1.54 (1.34-1.75) † / 0.44 / 0
Yoshitake(1999) / 111 / 525 / 0.39 / 0.27 / 1.45 (1.20-1.76)
Total / 483 / 1430
UC
Okada(2011) / 372 / 905 / 0.10 / 0.13 / 0.77 (0.60-0.98) / 0.005 / 0.74 (0.60-0.91) / 0.57 / 0
Futami (1995) / 59 / 150 / 0.19 / 0.28 / 0.67 (0.44-1.01)
Total / 431 / 1055
CD
*1501 / Okada (2011) / 372 / 905 / 0.04 / 0.07 / 0.62 (0.42-0.90) / 0.023 / 0.73 (0.52-1.02) / 0.23 / 32.1
Yoshitake (1999) / 111 / 525 / 0.11 / 0.12 / 0.87 (0.58-1.32)
Total / 483 / 1430
UC
Okada (2011) / 372 / 905 / 0.09 / 0.07 / 1.33 (1.01-1.76) / 0.106 / 1.18 (0.82-1.67) / 0.23 / 35.4
Yoshitake (1999) / 81 / 525 / 0.12 / 0.12 / 0.89(0.50-1.57)
Total / 453 / 1430
CD
*1502 / Okada(2011) / 372 / 905 / 0.06 / 0.14 / 0.43 (0.32-0.59) / 1.1E-12 / 0.49 (0.36-0.66) / 0.10 / 55.8
Sashio(2002) / 124 / 111 / 0.21 / 0.32 / 0.65 (0.48-0.88)
Yoshitake(1999) / 111 / 525 / 0.10 / 0.24 / 0.41 (0.27-0.61)
Total / 607 / 1541
UC
Okada (2011) / 372 / 905 / 0.28 / 0.14 / 2.00 (1.70-2.35) / 1.3E-37 / 2.17 (1.63-2.90) / 4.5E-4 / 83.3
Matsumura (2008) / 353 / 332 / 0.27 / 0.10 / 2.63 (2.03-3.39)
Sashio (2002) / 106 / 111 / 0.47 / 0.32 / 1.45 (1.15-1.84)
Futami(1995) / 59 / 150 / 0.49 / 0.16 / 3.07 (2.24-4.22)
Total / 890 / 1498
*Allele "1" denotes the reported risk allele. †OR and 95% CI were calculated using the inverse variancemethod or the DerSimonian-Laird method depending on the heterogeneity among studies. **combined P is considered of statistical significance when it is less than 1E-3 after the Bonferroni’scorrection because the meta-analysis was performed on 51 SNPs. a.rs2229094 is in high linkage disequilibrium with rs1799964 (r2 = 0.93). b.rs2844482 is in high linkage disequilibrium with rs1800630 (r2 = 1.0). c.rs2197423 is in high linkage disequilibrium with rs1801282 (r2 = 1.0). d.rs231735 is in high linkage disequilibrium with rs3087243 (r2 = 0.97). e.rs10850014 is in high linkage disequilibrium with rs2301756 (r2 = 1.0). f.rs11066322 is in high linkage disequilibrium with rs3741983 (r2 = 1.0). g.rs12952556 is in high linkage disequilibrium with rs1979277 (r2 = 1.0). h.rs352163 is in high linkage disequilibrium with rs187084, rs35214,and rs352139(r2 = 1.0). i.rs2569188 is in high linkage disequilibrium with rs2569190 (r2 = 1.0). j.rs1041981 is in high linkage disequilibrium with rs2071592 (r2 = 1.0). k.rs2071593 is in high linkage disequilibrium with rs3219184 (r2 = 1.0). l.rs795467 is in high linkage disequilibrium with rs549908(r2 = 1.0). RAF, risk allele frequency; OR, odds ratio; CI, confidence interval.
1