Table 1.
Association between HLA alleles and MS in UK Biobank and IMSGC cohort
| HLA allele | Test | UK Biobank | IMSGC | ||
|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | ||
| HLA-DRB1*15:01 | Additive effect | 3.16 (2.81–3.54) | 2.58 × 10−85 | 3.92 (3.74–4.12) | <1 × 10−600 |
| Homozygote correction | 0.67 (0.52–0.87) | 2.32 × 10−3 | 0.54 (0.47–0.61) | 8.50 × 10−22 | |
| HLA-A*02:01 | Additive effect | 0.69 (0.62–0.78) | 2.30 × 10−10 | 0.67 (0.64–0.70) | 7.80 × 10−70 |
| Homozygote correction | 1.20 (0.89–1.62) | 2.41 × 10−1 | 1.26 (1.13–1.41) | 3.30 × 10−05 | |
| HLA-DRB1*03:01 | Additive effect | 1.21 (1.06–1.37) | 3.39 × 10−3 | 1.16 (1.10–1.22) | 3.50 × 10−08 |
| Homozygote correction | 2.12 (1.53–2.94) | 6.84 × 10−6 | 2.58 (2.19–3.03) | 1.30 × 10−30 | |
| HLA-DRB1*13:03 | Additive effect | 2.10 (1.54–2.85) | 2.36 × 10−6 | 2.62 (2.32–2.96) | 6.20 × 10−55 |
| HLA-DRB1*08:01 | Additive effect | 1.56 (1.21–2.01) | 6.13 × 10−4 | 1.55 (1.42–1.69) | 1.00 × 10−23 |
| HLA-B*44:02 | Additive effect | 0.86 (0.74–0.98) | 2.94 × 10−2 | 0.78 (0.74–0.83) | 4.70 × 10−17 |
| HLA-B*38:01 | Additive effect | 0.29 (0.13–0.65) | 2.55 × 10−3 | 0.48 (0.42–0.56) | 8.00 × 10−23 |
| HLA-B*55:01 | Additive effect | 0.99 (0.75–1.31) | 9.47 × 10−1 | 0.63 (0.55–0.73) | 6.90 × 10−11 |
| HLA-DQA1*01:01 | Additive effect in the presence of HLA-DRB1*15:01 | 0.71 (0.56–0.90) | 5.33 × 10−3 | 0.65 (0.59–0.72) | 1.30 × 10−17 |
| HLA-DQB1*03:02 | Dominant effect | 1.07 (0.92–1.25) | 3.71 × 10−1 | 1.30 (1.23–1.37) | 1.80 × 10−22 |
| HLA-DQB1*03:01 | Allelic interaction with HLA-DQB1*03:02 | 0.8 (0.53–1.20) | 2.81 × 10−1 | 0.60 (0.52–0.69) | 7.10 × 10−12 |
Evidence for association between HLA alleles and MS in UK Biobank compared to the IMSGC cohort. The UK Biobank association tests involved 1,501 self-reported cases and 409,724 controls; the IMSGC cohort involved 17,465 cases and 30,385 controls31. Thus, the UK Biobank analysis had significantly lower power than the IMSGC analysis, which is reflected in the reported P values and larger confidence interval (CI) estimates for the odds ratios (OR). Effect sizes for the UK Biobank were estimated jointly using the logistic regression model of the MHC reported by the IMSGC (with the exception of the two SNPs rs9277565 and rs2229029). As in the IMSGC analysis, the homozygote correction test indicates a departure from additivity. That is, if the odds ratio is <1 then the homozygous effect is smaller than under the additivity assumption and bigger if it is >1. Reported P values were calculated using the Wald test.