Background
Methods
Study participants
Genotype imputation in the discovery phase
Direct genotyping in the replication phase
Statistical analysis for BD association
Results
Clinical characteristics of study participants
Characteristic | Discovery phase (n = 379) | Replication phase (n = 84) |
P valueb
|
---|---|---|---|
Male (%): female | 191 (50): 188 | 36 (43): 48 | |
Age at diagnosis of BD (years)a
| 41.6 ± 10.1 | 44.1 ± 11.4 | |
Clinical manifestation (%) | |||
Recurrent oral ulcer | 100 | 100 | |
Recurrent genital ulcer | 74.4 | 80.0 | |
Skin lesions | 89.2 | 96.3 | 0.04 |
Eye lesions | 43.5 | 28.8 | 0.01 |
Positive pathergy test | 54.6 (130/238) | 61.4 (27/44) | |
Vascular involvement | 16.4 | 17.5 | |
Central nervous system involvement | 11.6 | 3.8 | 0.03 |
Joint involvement | 41.4 | 51.3 |
LD structure comparison in Asian populations
Association analysis in the discovery phase
Locus | SNP | Risk allele (%) | HWE P
| Rsqc
| Allelic association | ||
---|---|---|---|---|---|---|---|
BD cases (n = 738) | Controls (n = 4000) | OR (95% CI) |
P
| ||||
IL23R–IL12RB2
| rs4655535 (G > T)a
| 467 (63) | 2201 (55) | 0.00023 | 0.40 | 1.4 (1.2, 1.7) | 0.000033 |
rs1495966 (T > C)a
| 467 (63) | 2204 (55) | 0.00042 | 0.40 | 1.4 (1.2, 1.7) | 0.000038 | |
rs1495965 (C > T)a
| 466 (63) | 2203 (55) | 0.00050 | 0.40 | 1.4 (1.2, 1.7) | 0.000049 | |
rs6665569 (T > C)a
| 465 (53) | 2210 (55) | 0.047 | 0.48 | 1.4 (1.2, 1.6) | 0.000094 | |
rs1966176 (G > A)a
| 506 (69) | 2442 (61) | 0.61 | 0.87 | 1.4 (1.2, 1.7) | 0.00011 | |
rs6677188 (T > A)a,b
| 588 (80) | 2919 (73) | 0.034 | NA | 1.4 (1.2, 1.8) | 0.00020 | |
rs924080 (T > C)a
| 590 (80) | 2940 (73) | 0.11 | 0.77 | 1.4 (1.2, 1.7) | 0.00022 | |
IL10
| rs1518110 (A > C) | 563 (76) | 2728 (68) | 0.47 | 0.91 | 1.5 (1.2, 1.8) | 0.000012 |
rs1518111 (T > C)a
| 563 (76) | 2728 (68) | 0.47 | 0.91 | 1.5 (1.2, 1.8) | 0.000012 | |
rs1800871 (A > G) | 563 (76) | 2728 (68) | 0.47 | 0.87 | 1.5 (1.2, 1.8) | 0.000012 | |
rs1800872 (T > G)a
| 563 (76) | 2728 (68) | 0.47 | 0.87 | 1.5 (1.2, 1.8) | 0.000012 | |
rs3024490 (A > C) | 563 (76) | 2728 (68) | 0.47 | 0.85 | 1.5 (1.2, 1.8) | 0.000012 | |
rs1554286 (A > G)a,b
| 551 (76) | 2720 (68) | 0.47 | NA | 1.5 (1.2, 1.8) | 0.000030 |
Association analysis in the replication phase
Locus | SNP | BD cases, risk allele/total (%) | Controls, risk allele/total (%) | Allelic association | |
---|---|---|---|---|---|
OR (95% CI) |
P
| ||||
IL23R–IL12RB2
| rs1495965 (C > T) | 106/168 (63) | 272/566 (48) | 1.9 (1.3, 2.6) | 0.00062 |
rs1495966 (T > C) | 106/168 (63) | 264/548 (48) | 1.8 (1.3, 2.6) | 0.00071 | |
rs4655535 (G > T) | 107/168 (64) | 277/566 (49) | 1.8 (1.3, 2.6) | 0.00078 | |
rs924080 (T > C) | 143/168 (85) | 413/566 (73) | 2.1 (1.3, 3.4) | 0.0013 | |
rs1966176 (G > A) | 118/168 (70) | 322/562 (57) | 1.8 (1.2, 2.6) | 0.0026 | |
rs6677188 (T > A) | 142/168 (85) | 419/566 (74) | 1.9 (1.2, 3.0) | 0.0049 | |
rs6665569 (T > C) | 103/168 (61) | 271/550 (49) | 1.6 (1.2, 2.3) | 0.0063 | |
IL10
| rs1518111 (A > G) | 120/168 (71) | 408/566 (72) | 1.0 (0.7, 1.4) | 0.87 |
rs1800872 (A > C) | 120/168 (71) | 408/566 (72) | 1.0 (0.7, 1.4) | 0.87 | |
rs1554286 (T > C) | 120/168 (71) | 396/554 (71) | 1.0 (0.7, 1.5) | 0.99 |
Meta-analysis
SNP | Phase | BD cases, risk allele/total | Controls, risk allele/total | Weight % |
I
2 % | OR (95% CI) |
P
|
---|---|---|---|---|---|---|---|
rs1495965 | Dis. | 467/738 (63) | 2203/4000 (55) | 83.7 | 35 | 1.41 (1.20, 1.65) | 0.000049 |
Rep. | 106/168 (63) | 272/566 (48) | 16.3 | 1.85 (1.30, 2.63) | 0.00060 | ||
Total | 573/906 (63) | 2475/4566 (54) | 1.47 (1.27, 1.70) | 0.00000025 | |||
rs4655535 | Dis. | 467/738 (63) | 2201/4000 (55) | 83.7 | 27 | 1.41 (1.20, 1.66) | 0.000033 |
Rep. | 107/168 (64) | 277/566 (49) | 16.3 | 1.83 (1.28, 2.61) | 0.00080 | ||
Total | 574/906 (63) | 2478/4566 (54) | 1.47 (1.27, 1.71) | 0.00000026 | |||
rs1495966 | Dis. | 467/738 (63) | 2204/4000 (55) | 83.4 | 0 | 1.40 (1.19, 1.64) | 0.000038 |
Rep. | 106/168 (63) | 264/548 (48) | 16.6 | 1.84 (1.29, 2.62) | 0.00070 | ||
Total | 573/906 (63) | 2464/4548 (54) | 1.47 (1.27, 1.70) | 0.00000029 | |||
rs1966176 | Dis. | 506/738 (69) | 2443/4000(61) | 83.6 | 5 | 1.39 (1.18, 1.64) | 0.00011 |
Rep. | 118/168 (70) | 322/562 (57) | 16.4 | 1.76 (1.21, 2.55) | 0.0026 | ||
Total | 624/906 (69) | 2765/4562 (61) | 1.45 (1.24, 1.69) | 0.0000021 | |||
rs6665569 | Dis. | 465/738 (53) | 2210/4000 (55) | 83.0 | 0 | 1.38 (1.17, 1.62) | 0.000094 |
Rep. | 103/168 (61) | 271/550 (49) | 17.0 | 1.63 (1.15, 2.32) | 0.0063 | ||
Total | 568/906 (63) | 2481/4550 (55) | 1.42 (1.23, 1.65) | 0.0000030 | |||
rs924080 | Dis. | 590/738 (80) | 2940/4000 (74) | 86.4 | 62 | 1.44 (1.18, 1.74) | 0.00022 |
Rep. | 143/168 (85) | 413/566 (73) | 13.6 | 2.12 (1.33, 3.37) | 0.0013 | ||
Total | 733/906 (81) | 3353/4566 (73) | 1.53 (1.28, 1.83) | 0.0000032 | |||
rs6677188 | Dis. | 590/738 (80) | 2937/4000 (73) | 85.8 | 34 | 1.44 (1.19, 1.75) | 0.00019 |
Rep. | 142/168 (85) | 419/566 (74) | 14.2 | 1.92 (1.21, 3.03) | 0.0049 | ||
Total | 732/906 (81) | 3356/4566 (73) | 1.51 (1.26, 1.80) | 0.0000060 |