Table 2. Newly associated IBD risk loci.
The IBD, ulcerative colitis or Crohn’s disease loci are identified through a trans-ethnic analysis of genome-wide and Immunochip genotype data from a cohort of 86,682 European individuals and 9,846 individuals of non-European descent. Loci achieving genome-wide significance (P < 5 × 10-8) in one of the individual cohorts of European (Eur), East Asian, Indian or Iranian descent, or a log10 Bayes Factor > 6.0 in the combined trans-ethnic association analysis, are considered significantly associated loci. Loci having a logBF>6 but P>5×10-8 in each individual ancestral cohort were required to show no significant evidence of heterogeneity across all four ancestry groups (I2> 85.7). Association P-values and ORs of non-European cohorts are given in Supplementary Table 2.
| Ch r. | SNP | BP positio n | aReference allele | bBest phenotype | cLR phenotype | dLog1 0 BF | eHet I2 | Eur. OR | Eur. P | Candidate Genes |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | rs1748195 | 63049593 | G | CD | CD | 6.08 | 0 | 1.07 (1.04-1.1) | 7.13×10-8 | USP1 |
| 1 | rs34856868 | 92554283 | A | IBD | IBD_U | 6.16 | 0 | 0.82 (0.77-0.88) | 9.80×10-9 | BTBD8 |
| 1 | rs11583043 | 101466054 | A | UC | IBD_U | 8.34 | 66.5 | 1.08 (1.05-1.11) | 6.05×10-8 | SLC30A, EDG1 |
| 1 | rs6025 | 169519049 | A | IBD | IBD_U | 6.43 | 0 | 0.84 (0.79-0.89) | 2.51×10-8 | SELP,SELE,SE LL |
| 1 | rs10798 069 | 186875459 | A | CD | IBD_S | 7.24 | 0 | 0.93 (0.91-0.95) | 4.25×10-9 | PTGS2,PLA2G 4A |
| 1 | rs7555082 | 198598663 | A | CD | IBD_U | 7.97 | 0 | 1.13 (1.09-1.17) | 1.47×10-10 | PTPRC |
| 2 | rs11681 525 | 145492382 | C | CD | CD | 8.8 | 59.3 | 0.86 (0.82-0.90) | 4.08×10-11 | - |
| 2 | rs4664304 | 160794008 | A | IBD | IBD_U | 6.34 | 0 | 1.06 (1.04-1.08) | 2.61×10-8 | MARCH7,LY75,PLA2R1 |
| 2 | rs31164 94 | 204592021 | G | UC | IBD_S | 7.03 | 0 | 1.08 (1.05-1.11) | 1.30×10-7 | ICOS,CD28,CT LA4 |
| 2 | rs11178 1203 | 228660112 | G | IBD | IBD_U | 10.04 | 0 | 0.94 (0.92-0.96) | 2.16×10-10 | CCL20 |
| 2 | rs35320 439 | 242737341 | G | CD | IBD_S | 7.71 | 0 | 1.09 (1.06-1.12) | 9.89×10-10 | PDCD1,ATG4B |
| 3 | rs11301 0081 | 46457412 | G | UC | IBD_U | 7.45 | 0 | 1.14 (1.09-1.19) | 9.02×10-10 | FLJ78302,LTF, CCR1,CCR2, CCR3,CCR5 |
| 3 | rs616597 | 101569726 | A | UC | UC | 6.68 | 54.7 | 0.93 (0.90-0.96) | 9.34×10-6 | NFKBIZ |
| 3 | rs724016 | 141105570 | G | CD | CD | 7.41 | 70.9 | 1.06 (1.04-1.09) | 3.36×10-6 | - |
| 4 | rs2073505 | 3444503 | A | IBD | IBD_U | 6.87 | 0 | 1.1 (1.06-1.14) | 1.46×10-7 | HGFAC |
| 4 | rs4692386 | 26132361 | A | IBD | IBD_U | 6.47 | 0 | 0.94 (0.92-0.96) | 1.21×10-8 | - |
| 4 | rs6856616 | 38325036 | G | IBD | IBD_U | 9.78 | 61.6 | 1.1 (1.06-1.14) | 9.72×10-7 | - |
| 4 | rs2189234 | 106075498 | A | UC | UC | 8.85 | 0 | 1.08 (1.05-1.11) | 1.95×10-10 | - |
| 5 | rs395157 | 38867732 | A | IBD | IBD_U | 19.5 | 0 | 1.1 (1.08-1.12) | 2.22×10-20 | OSMR,FYB, LIFR |
| 5 | rs4703855 | 71693899 | A | IBD | IBD_U | 6.83 | 70.3 | 0.93 (0.91-0.95) | 7.16×10-11 | - |
| 5 | rs564349 | 172324978 | G | IBD | IBD_U | 8.12 | 37.5 | 1.06 (1.04-1.08) | 1.54×10-7 | C5orf4, DUSP1 |
| 6 | rs7773324 | 382559 | G | CD | IBD_U | 7.67 | 0 | 0.92 (0.90-0.94) | 1.06×10-9 | IRF4,DUSP22 |
| 6 | rs13204048 | 3420406 | G | CD | IBD_S | 7.23 | 53.5 | 0.93 (0.91-0.95) | 2.89×10-8 | - |
| 6 | rs7758080 | 149577079 | G | CD | IBD_S | 7.88 | 0 | 1.08 (1.05-1.11) | 7.27×10-9 | MAP3K7IP2 |
| 7 | rs1077773 | 17442679 | G | UC | UC | 5.86 | 76.7 | 0.93 (0.91-0.95) | 5.96×10-9 | AHR |
| 7 | rs2538470 | 148220448 | A | IBD | IBD_U | 10.93 | 54.6 | 1.07 (1.05-1.09) | 3.00×10-11 | CNTNAP2 |
| 8 | rs17057051 | 27227554 | G | IBD | IBD_U | 6.74 | 15.9 | 0.94 (0.92-0.96) | 5.50×10-8 | PTK2B,TRIM 35,EPHX2, |
| 8 | rs7011507 | 49129242 | A | UC | IBD_U | 7.49 | 39.3 | 0.9 (0.87-0.93) | 6.40×10-8 | - |
| 10 | rs3740415 | 104232716 | G | IBD | IBD_U | 6.26 | 0 | 0.95 (0.93-0.97) | 1.03×10-7 | NFKB2, TRIM8, TMEM180 |
| 12 | rs7954567 | 6491125 | A | CD | CD | 8.25 | 0 | 1.09 (1.06-1.12) | 1.30×10-9 | CD27,TNFRSF 1A,LTBR |
| 12 | rs653178 | 112007756 | G | IBD | IBD_U | 6.57 | 49.7 | 1.06 (1.04-1.08) | 1.11×10-8 | SH2B3, ALDH2,ATXN 2 |
| 12 | rs11064881 | 120146925 | A | IBD | IBD_U | 7.02 | 31.7 | 1.1 (1.06-1.14) | 5.95×10-8 | PRKAB1 |
| 13 | rs9525625 | 43018030 | A | CD | CD | 8.55 | 37.3 | 1.08 (1.05-1.11) | 1.41×10-9 | AKAP1, TFSF11 |
| 17 | rs3853824 | 54880993 | A | CD | IBD_S | 8.46 | 50.4 | 0.92 (0.90-0.94) | 1.17×10-10 | - |
| 17 | rs17736589 | 76737118 | G | UC | UC | 6.53 | 53.4 | 1.09 (1.06-1.12) | 4.34×10-8 | - |
| 18 | rs9319943 | 56879827 | G | CD | CD | 6.33 | 33.4 | 1.08 (1.05-1.11) | 9.05×10-7 | - |
| 18 | rs7236492 | 77220616 | A | CD | IBD_S | 6.6 | 0 | 0.91 (0.88-0.94) | 9.09×10-9 | NFATC1, TST |
| 22 | rs727563 | 41867377 | G | CD | CD | 7.1 | 76 | 1.1 (1.07-1.13) | 1.88×10-10 | TEF, NHP2L1, PMM1, L3MBTL2, CHADL |
The minor allele in the European cohort was chosen to be the reference allele.
Phenotype with the largest MANTRA Bayes factor
The preferred phenotype (ulcerative colitis, Crohn’s disease or IBD (i.e. both)) from our likelihood modeling approach to classify loci according to their relative strength of association. IBD_S and IBD_U refer to the IBD saturated and IBD unsaturated models, respectively (see main text and Online Methods).
MANTRA log10 Bayes Factor.
Heterogeneity I2 percentage. Candidate genes are identified by one of the gene prioritization methods we performed (eQTL, GRAIL, DAPPLE and cSNP annotation - see main text and Online Methods). Genes in bold are prioritized by > 2 gene prioritization strategies. UC, Ulcerative Colitis; CD, Crohn’s Disease; IBD, Inflammatory Bowel Disease; BP, Base Position; Chr, chromosome; OR, odds ratio.