Fig. 4: MR to estimate the causal associations for 17 genetically determined risk factors on forearm fracture risk.

Data are given as OR with 95% CIs estimated using IVW MR. OR for the risk of fracture are given per s.d. change in the risk factor for continuous trait or risk of fracture per doubling of odds (obtained by multiplying the causal estimate of log odds by ln₂ ≈ 0.693) (ref. ⁴¹) of disease susceptibility for binary factors. For menopause and puberty, we used the estimated s.d. from the largest cohorts in the published GWAS (early menopause s.d. = 3.81 in Breast Cancer Association Consortium²⁹; late puberty s.d. = 1.40 in Women’s Genome Health Study³⁰) to translate the effect unit from year to s.d. For ever smoked regularly, ORs are expressed per unit increase in log odds of ever smoking regularly with a 1 s.d. increase in genetically predicted smoking initiation corresponding to a 10% increased risk of smoking^38,42. Grip strength is given as grip strength per BW and s.d. for grip strength is given for kg grip strength per kg in BW and was estimated in the UK Biobank to be 0.127. P < 0.0029 (Bonferroni correction accounting for 17 tests) was considered statistically significant. Findings with a nonadjusted P value (based on a two-sided z test) below 0.0029 have their corresponding P value represented in the figure. For risk factors including UK Biobank in the GWAS and displaying statistically significant causal effects with forearm fractures, we performed sensitivity analyses excluding UK Biobank in the forearm fracture meta-analysis used for the MR, revealing essentially similar effect estimates (results excluding UK Biobank in the forearm fracture GWAS; decreased eBMD OR = 2.07; 95% CI, 1.96–2.20; P = 1.0 × 10⁻¹³⁷; early menopause OR = 1.10; 95% CI, 1.02–1.18; P = 1.5 × 10⁻²).