Table 1.
Genome Wide Significant Associations and Maximal Established Loci Replications
Genome Wide Significant Associations and Established Loci Replications for UC, CD and IBD. The 1000Genomes Project phase 3 allele frequencies for various populations is included.
| Phenotyp e |
Chr | Position | A1 | A2 | SNP Name | GWAS1 (Omni2.5) | GWAS2 (Axiom) | Meta-analysis | Nearest Gene(s) | Annotatio n |
Significance Level |
MAF (Minor Allele) |
African Sub-populations with highest MAF |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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| P-Value | Case Freq |
Control Freq |
OR | 95% CI | P-Value | Case Freq |
Control Freq |
OR | 95% CI | OR | P-value | YRI | EAS | EUR | SAS | ||||||||||
| UC | 6 | 32559063 | A | C | rs9270484 | 1.45E-07 | 0.448 | 0.356 | 0.68 | 0.58 – 0.8 | 4.41E-07 | 0.426 | 0.319 | 0.63 | 0.52 – 0.76 | 0.58 | 3.22E-12 | HLA-DRB1 | intergenic | GWS | 0.11 (C) | 0.31 (C) | 0.31 (C) | 0.3 (C) | |
| 6 | 32557435 | A | C | rs9270299 | 5.98E-08 | 0.284 | 0.207 | 0.66 | 0.55 – 0.79 | 1.06E-05 | 0.281 | 0.209 | 0.68 | 0.55 – 0.83 | 0.52 | 2.65E-11 | HLA-DRB1 | exonic | GWS | 0.15 (A) | 0.16 (A) | 0.12 (A) | 0.24 (A) | ||
| 6 | 32552617 | G | A | rs28724138 | 4.62E-07 | 0.412 | 0.487 | 0.74 | 0.62 – 0.87 | 2.75E-06 | 0.572 | 0.482 | 0.70 | 0.58 – 0.84 | 0.57 | 4.70E-11 | HLA-DRB1 | intronic | GWS | 50 (A) | 47 (A) | 47 (G) | 49 (A) | ||
| 19 | 52400451 | G | A | rs78090981 * | 9.65E-06 | 0.054 | 0.026 | 2.16 | 1.46 – 3.21 | 1.54E-05 | 0.051 | 0.022 | 2.42 | 1.55 – 3.78 | 3.64 | 9.93E-10 | ZNF649 | intronic | GWS | 0.06 (A) | 0 (A) | 0 (A) | 0 (A) | YRI - 0.06 (A) | |
| 3 | 115528296 | C | T | rs72947885 * | 5.19E-08 | 0.099 | 0.054 | 1.91 | 1.43 – 2.56 | 8.07E-03 | 0.080 | 0.051 | 1.62 | 1.14 – 2.3 | 2.42 | 4.48E-09 | LSAMP | UTR3 | GWS | 0.07 (T) | 0 (T) | 0 (T) | 0 (T) | LWK - 0.12 (T) | |
| 20 | 62100266 | T | G | rs914467 | 1.72E-02 | 0.101 | 0.071 | 1.46 | 1.11 – 1.93 | 1.23E-06 | 0.140 | 0.093 | 1.59 | 1.21 – 2.09 | 1.97 | 5.91E-07 | KCNQ2 | intronic | Locus Replication | 0.02 (G) | 0.15 (G) | 0.24 (G) | 0.14 (G) | ||
| 9 | 117811778 | C | T | rs114032850 * | 4.04E-05 | 0.078 | 0.042 | 1.91 | 1.38 – 2.64 | 1.78E-02 | 0.065 | 0.041 | 1.61 | 1.1 – 2.38 | 2.06 | 3.68E-06 | TNC | intronic | 0.06 (T) | 0 (T) | 0 (T) | 0 (T) | MAG - 0.09 (T) | ||
| 3 | 101641101 | A | T | rs141365838 | 4.72E-02 | 0.111 | 0.082 | 1.39 | 1.06 – 1.81 | 2.55E-06 | 0.166 | 0.106 | 1.68 | 1.3 – 2.17 | 1.67 | 3.90E-06 | NFKBIZ | intergenic | 0.1 (T) | 0.1 (T) | 0.22 (T) | 0.2 (T) | |||
| 20 | 62308570 | A | G | rs2738782 | 6.15E-06 | 0.152 | 0.099 | 0.61 | 0.48 – 0.78 | 7.20E-01 | 0.162 | 0.167 | 1.03 | 0.8 – 1.33 | 0.45 | 8.21E-06 | RTEL1:TNFRSF6B | intronic | 0.05 (A) | 0.42 (G) | 0.41 (A) | 0.37 (A) | |||
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| CD | 16 | 50709723 | G | A | rs6596 | 3.55E-05 | 0.058 | 0.032 | 1.91 | 1.42 – 2.56 | 3.14E-04 | 0.062 | 0.049 | 1.28 | 1 – 1.64 | 2.06 | 1.14E-07 | SNX20 | exonic | Locus Replication | 0 (A) | 0 (A) | 0.16 (A) | 0.01 (A) | |
| 5 | 40424426 | A | C | rs6896969 | 5.46E-04 | 0.333 | 0.387 | 1.26 | 1.11 – 1.44 | 4.22E-05 | 0.330 | 0.391 | 1.30 | 1.15 – 1.47 | 1.28 | 1.69E-07 | PTGER4 | intergenic | Locus Replication | 0.38 (A) | 0.14 (C) | 0.41 (A) | 0.45 (C) | ||
| 1 | 67665210 | A | G | rs1569923 | 2.91E-05 | 0.434 | 0.362 | 0.74 | 0.65 – 0.84 | 8.37E-04 | 0.425 | 0.389 | 0.86 | 0.76 – 0.97 | 0.78 | 1.88E-07 | IL23R | intronic | Locus Replication | 0.36 (A) | 0.39 (G) | 0.37 (G) | 0.37 (G) | ||
| 21 | 16799818 | G | A | rs7276764 | 7.76E-03 | 0.277 | 0.314 | 0.84 | 0.73 – 0.96 | 3.01E-05 | 0.276 | 0.320 | 0.81 | 0.71 – 0.92 | 0.76 | 2.59E-06 | USP25 | intergenic | 0.34 (A) | 0.24 (A) | 0.29 (A) | 0.23 (A) | |||
| 2 | 25145173 | T | A | rs59086897 | 9.54E-03 | 0.192 | 0.204 | 1.08 | 0.92 – 1.26 | 4.54E-05 | 0.199 | 0.259 | 1.41 | 1.22 – 1.63 | 1.33 | 4.00E-06 | ADCY3 | intergenic | 0.08 (T) | 0.44 (A) | 0.47 (A) | 0.48 (A) | |||
| 6 | 167541624 | T | C | rs41414848 * | 2.88E-02 | 0.069 | 0.089 | 0.76 | 0.6 – 0.96 | 7.09E-06 | 0.040 | 0.068 | 0.58 | 0.44 – 0.77 | 0.64 | 4.42E-06 | CCR6 | intronic | 0.09 (C) | 0 (C) | 0 (C) | 0 (C) | ESN - 0.12 (C) | ||
| 4 | 106934908 | C | A | rs6854424 * | 3.60E-05 | 0.055 | 0.033 | 1.71 | 1.27 – 2.3 | 2.75E-02 | 0.041 | 0.028 | 1.47 | 1.08 – 1.99 | 1.85 | 5.86E-06 | TBCK | intronic | 0.04 (A) | 0 (A) | 0 (A) | 0 (A) | MAG / MSL - 0.06 (A) | ||
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| IBD | 21 | 16800087 | C | T | rs7278277 | 1.60E-04 | 0.530 | 0.473 | 0.80 | 0.71 – 0.89 | 1.21E-05 | 0.513 | 0.476 | 0.86 | 0.78 – 0.96 | 0.77 | 1.99E-08 | USP25 | intergenic | GWS | 0.43 (C) | 0.24 (T) | 0.29 (T) | 0.23 (T) | |
| 5 | 40424426 | A | C | rs6896969 | 4.09E-04 | 0.340 | 0.387 | 1.22 | 1.09 – 1.37 | 2.85E-05 | 0.335 | 0.391 | 1.27 | 1.14 – 1.42 | 1.25 | 7.81E-08 | PTGER4 | intergenic | Locus Replication | 0.38 (A) | 0.14 (C) | 0.41 (A) | 0.45 (C) | ||
| 6 | 32594240 | T | A | rs139282044 * | 5.48E-05 | 0.050 | 0.031 | 1.67 | 1.26 – 2.21 | 1.74E-04 | 0.038 | 0.022 | 1.76 | 1.31 – 2.36 | 1.93 | 9.43E-08 | HLA-DQA1 | intergenic | Locus Replication | 0.04 (A) | 0 (A) | 0 (A) | 0 (A) | ESN - 0.08 (A) | |
| 9 | 117811778 | C | T | rs114032850 * | 3.14E-05 | 0.066 | 0.042 | 1.61 | 1.26 – 2.05 | 4.00E-04 | 0.063 | 0.041 | 1.56 | 1.24 – 1.95 | 1.65 | 9.59E-08 | TNC | intronic | Locus Replication | 0.06 (T) | 0 (T) | 0 (T) | 0 (T) | MAG - 0.09 (T) | |
| 5 | 158782684 | C | T | rs11749526 | 3.20E-05 | 0.020 | 0.034 | 0.58 | 0.41 – 0.83 | 9.64E-04 | 0.023 | 0.042 | 0.54 | 0.39 – 0.75 | 0.53 | 2.64E-07 | LOC285626: IL12B | intronic | Locus Replication | 0 (T) | 0.08 (T) | 0.14 (T) | 0.05 (T) | ||
| 3 | 45989578 | C | G | rs55698153 * | 1.82E-05 | 0.050 | 0.075 | 0.64 | 0.51 – 0.81 | 7.67E-03 | 0.037 | 0.049 | 0.75 | 0.57 – 0.98 | 0.60 | 6.94E-07 | CXCR6 | UTR3 | Locus Replication | 0.06 (G) | 0 (G) | 0 (G) | 0 (G) | YRI / ESN / LWK - 0.06 (G) | |
| 2 | 25145173 | T | A | rs59086897 | 3.58E-03 | 0.191 | 0.204 | 1.09 | 0.95 – 1.25 | 3.72E-05 | 0.204 | 0.259 | 1.36 | 1.2 – 1.55 | 1.31 | 1.18E-06 | ADCY3 | intergenic | Locus Replication | 0.08 (T) | 0.44 (A) | 0.47 (A) | 0.48 (A) | ||
| 1 | 67630341 | A | T | rs10889663 | 8.74E-03 | 0.299 | 0.331 | 0.86 | 0.77 – 0.97 | 3.46E-05 | 0.274 | 0.313 | 0.83 | 0.74 – 0.93 | 0.78 | 2.60E-06 | IL23R | intergenic | Observed variant without frequency or population information | ||||||
| 6 | 167541624 | T | C | rs41414848 * | 4.04E-02 | 0.071 | 0.089 | 0.78 | 0.64 – 0.96 | 1.50E-06 | 0.042 | 0.068 | 0.61 | 0.48 – 0.78 | 0.67 | 3.50E-06 | CCR6 | intronic | 0.09 (C) | 0 (C) | 0 (C) | 0 (C) | ESN - 0.12 (C) | ||
| 1 | 120553996 | C | T | rs7530844 | 3.63E-05 | 0.215 | 0.157 | 1.47 | 1.27 – 1.69 | 1.61E-02 | 0.230 | 0.233 | 0.99 | 0.87 – 1.12 | 1.33 | 8.32E-06 | NOTCH2 | intronic | 0.02 (T) | 0.23 (C) | 0.18 (C) | 0.4 (C) | |||
| 5 | 150596303 | C | T | rs13359932 | 1.01E-05 | 0.230 | 0.288 | 0.74 | 0.65 – 0.84 | 5.00E-02 | 0.238 | 0.248 | 0.95 | 0.84 – 1.07 | 0.80 | 9.06E-06 | CCDC69 | intronic | 0.31 (T) | 0 (T) | 0.01 (T) | 0 (T) | |||
Top associations per locus for UC, CD and IBD. The top 3 HLA associations are shown for illustrative purposes.
Chr: Chromosome; A1: tested allele; A2: Alternate allele; Freq: Tested allele frequency; OR: odds ratio; CI: Confidence interval; GWS: Genome-wide significant; MAF: Minor Allele Frequency.
"Locus replication" defined as p<1.5×10−6 at SNP within 250 kb of a maximal association of a previously established locus.
YRI: Yoruba in Ibadan, Nigeria; EAS: East Asian; EUR: European; SAS: South Asian; LWK: Luhya in Webuye, in Kenya; MAG: Mandinka in Gambia; ESN: Esan in Nigeria; MSL: Mende in Sierra Leone; (data from 1000 genome phase 3)
*
African Specific SNP (monomorphic in EAS, EUR ans SAS)