Table 1.
Genome-wide significant association signals in the myasthenia gravis GWAS
| Discovery | Replication | Meta-analysis | |||||||||
| Chr | Position (SNPid) | Nearest gene | EA/OA | Cohort | EAF | OR (95% CI) | P | EAF | OR (95% CI) | P | P |
| 1 | 113834946 (rs2476601) | PTPN22 | A/G | All | 0.101/0.093 | 1.49 (1.32–1.67) | 7.95 × 10−11 | 0.141/0.107 | 1.36 (1.10–1.69) | 5.11 × 10−3 | 1.85 × 10−12 |
| M | 0.111/0.093 | 1.60 (1.38–1.86) | 6.50 × 10−10 | 0.135/0.107 | 1.30 (0.96–1.76) | 9.59 × 10−2 | 7.73 × 10−10 | ||||
| F | 0.089/0.093 | 1.34 (1.12–1.59) | 1.35 × 10−3 | 0.147/0.107 | 1.41 (1.05–1.90) | 2.38 × 10−2 | 1.15 × 10−4 | ||||
| 2 | 174764492 (rs35274388) | CHRNA1 | A/G | All | 0.057/0.036 | 1.57 (1.34–1.84) | 3.07 × 10−8 | 0.047/0.03 | 1.60 (1.11–2.31) | 1.17 × 10−2 | 1.18 × 10−9 |
| M | 0.063/0.036 | 1.77 (1.46–2.15) | 8.06 × 10−9 | 0.066/0.03 | 2.34 (1.52–3.60) | 1.13 × 10−4 | 7.19 × 10−12 | ||||
| F | 0.051/0.036 | 1.34 (1.06–1.71) | 1.48 × 10−2 | 0.026/0.03 | 0.86 (0.44–1.70) | 0.67 | 4.42 × 10−2 | ||||
| 6 | 31358836 (*rs9266277) | HLA-B | A/G | All | 0.361/0.347 | 1.29 (1.20–1.40) | 3.30 × 10−11 | 0.395/0.385 | 1.04 (0.89–1.22) | 0.61 | 6.70 × 10−10 |
| M | 0.323/0.347 | 1.09 (0.99–1.21) | 8.10 × 10−2 | 0.41/0.385 | 1.09 (0.89–1.35) | 0.40 | 6.64 × 10−2 | ||||
| F | 0.403/0.347 | 1.60 (1.44–1.78) | 7.15 × 10−18 | 0.379/0.385 | 0.98 (0.79–1.22) | 0.86 | 1.19 × 10−13 | ||||
| 6 | 32620936 (rs76815088) | HLA-DQA1 | C/T | All | 0.024/0.061 | 0.42 (0.34–0.52) | 1.58 × 10−14 | 0.028/0.052 | 0.54 (0.34–0.84) | 6.37 × 10−3 | 5.70 × 10−16 |
| M | 0.021/0.061 | 0.37 (0.27–0.50) | 5.55 × 10−10 | 0.03/0.052 | 0.58 (0.32–1.06) | 7.47 × 10−2 | 2.82 × 10−10 | ||||
| F | 0.027/0.061 | 0.53 (0.39–0.71) | 2.73 × 10−5 | 0.026/0.052 | 0.50 (0.26–0.96) | 3.89 × 10−2 | 3.25 × 10−6 | ||||
| 10 | 7410781 (rs2245569) | SFMBT2 | G/A | All | 0.277/0.213 | 1.27 (1.17–1.38) | 1.66 × 10−8 | 0.216/0.205 | 1.07 (0.89–1.28) | 0.49 | 5.58 × 10−8 |
| M | 0.278/0.213 | 1.28 (1.15–1.42) | 5.82 × 10−6 | 0.232/0.205 | 1.16 (0.91–1.49) | 0.23 | 4.08 × 10−6 | ||||
| F | 0.275/0.213 | 1.26 (1.12–1.41) | 7.73 × 10−5 | 0.199/0.205 | 0.97 (0.74–1.27) | 0.82 | 3.47 × 10−4 | ||||
| 11 | 95578258 (rs4409785) | FAM76B | C/T | All | 0.217/0.174 | 1.29 (1.18–1.41) | 1.54 × 10−8 | 0.171/0.172 | 1.00 (0.81–1.22) | 0.97 | 2.42 × 10−7 |
| M | 0.220/0.174 | 1.30 (1.16–1.45) | 6.88 × 10−6 | 0.188/0.172 | 1.11 (0.85–1.45) | 0.44 | 1.47 × 10−5 | ||||
| F | 0.213/0.174 | 1.27 (1.12–1.43) | 2.11 × 10−4 | 0.153/0.172 | 0.88 (0.65–1.18) | 0.39 | 2.59 × 10−3 | ||||
| 18 | 62342581 (rs4574025) | TNFRSF11A | C/T | All | 0.535/0.461 | 1.33 (1.24–1.43) | 7.08 × 10−15 | 0.492/0.474 | 1.09 (0.93–1.27) | 0.30 | 7.12 × 10−14 |
| M | 0.559/0.461 | 1.47 (1.33–1.61) | 2.27 × 10−15 | 0.526/0.474 | 1.23 (1.00–1.53) | 5.13 × 10−2 | 2.60 × 10−15 | ||||
| F | 0.508/0.461 | 1.20 (1.09–1.33) | 4.08 × 10−4 | 0.457/0.474 | 0.94 (0.76–1.17) | 0.59 | 4.06 × 10−3 | ||||
Significant hits were stratified by sex to determine the contribution of sex and are highlighted in bold. Positions were in build hg38; Chr, chromosome; EA/OA, effect allele/other allele; EAF, effect allele frequency in cases and controls; discovery, meta-analysis from the US and Italian cohorts (1,873 cases [989 male, 884 female] and 33,370 controls); replication, cohort from the UK Biobank where controls were age- and sex-matched (354 cases [181 male, 173 female] and 7,078 controls); *rs9266277 is an independent variant identified from conditional analysis on rs76815088. Results in the table are from the unconditional analysis. Discovery phase conditional statistics for rs9266277: OR (95% CI) = 1.28 (1.19–1.38), P = 1.92 × 10−10. The replication significance threshold was set at P = 0.1/7 = 0.0143 (Bonferroni correction for seven loci with the same effect direction).