Table 1.
Genetically predicted age at menarche, age at menopause and, age at first birth with the risk of rheumatoid arthritis. Results from primary Mendelian randomization analysis as well as sensitivity analyses based on a subset of instruments
| Methods | #SNP | OR (95% CI) | P-value | #SNP | OR (95% CI) | P-value | #SNP | OR (95% CI) | P-value |
|---|---|---|---|---|---|---|---|---|---|
| Full set | Remove palindromic SNPs | Remove confounding SNPs | |||||||
| Age at menarche | |||||||||
| IVW | 340 | 1.06 (0.98–1.15) | 0.11 | 284 | 1.06 (0.97–1.15) | 0.19 | 283 | 1.03 (0.94–1.12) | 0.57 |
| Maximum likelihood | 340 | 1.07 (1.00–1.14) | 0.06 | 284 | 1.06 (0.99–1.14) | 0.12 | 283 | 1.03 (0.95–1.11) | 0.50 |
| MR-Egger | 340 | 1.11 (0.90–1.36) | 0.34 | 284 | 1.08 (0.85–1.37) | 0.51 | 283 | 0.97 (0.72–1.30) | 0.83 |
| MR-Egger intercept | 0.69 | 0.85 | 0.68 | ||||||
| Weighted median | 340 | 1.08 (0.97–1.21) | 0.15 | 284 | 1.10 (0.97–1.25) | 0.12 | 283 | 1.01 (0.90–1.14) | 0.86 |
| Age at natural menopause | |||||||||
| IVW | 54 | 1.05 (0.98–1.11) | 0.15 | 47 | 1.05 (0.98–1.13) | 0.13 | 42 | 1.04 (0.95–1.14) | 0.40 |
| Maximum likelihood | 54 | 1.05 (1.02–1.08) | 4 × 10−3 | 47 | 1.06 (1.02–1.10) | 9 × 10−4 | 42 | 1.05 (1.00–1.10) | 0.05 |
| MR-Egger | 54 | 1.04 (0.90–1.20) | 0.61 | 47 | 1.05 (0.90–1.23) | 0.51 | 42 | 1.05 (0.74–1.48) | 0.79 |
| MR-Egger intercept | 0.92 | 0.99 | 0.96 | ||||||
| Weighted median | 54 | 1.03 (0.98–1.08) | 0.30 | 47 | 1.05 (1.00–1.11) | 0.07 | 42 | 0.94 (0.88–1.01) | 0.09 |
| Age at first birth | |||||||||
| IVW | 10 | 0.85 (0.65–1.10) | 0.22 | 9 | 0.81 (0.61–1.07) | 0.14 | NA | NA | NA |
| Maximum likelihood | 10 | 0.84 (0.73–0.97) | 0.02 | 9 | 0.81 (0.70–0.94) | 5 × 10−3 | NA | NA | NA |
| MR-Egger | 10 | 3.32 (0.36–30.81) | 0.32 | 9 | 3.05 (0.33–28.49) | 0.36 | NA | NA | NA |
| MR-Egger intercept | 0.26 | 0.28 | NA | NA | NA | ||||
| Weighted median | 10 | 0.90 (0.73–1.10) | 0.30 | 9 | 0.85 (0.69–1.05) | 0.13 | NA | NA | NA |
NA none of the 10 age at first birth associated SNPs was found to be associated with other traits according to GWAS catalog, IVW inverse-variance weighted method, OR odds ratio, the risk of developing rheumatoid arthritis per-SD increment in age at menarche, age at natural menopause, or age at first birth