Reproductive factors (AFS, LNSP and AFB)
In the MVMR analyses, we arrived at a result of causality between later
age at first sexual intercourse and MA: reverse causality, by adjusting
LNSP (AFS in model 5, OR=0.831, 95%CI, 0.785-0.880, P=1.64E-10). An
increase in LNSP indicated greater likelihood of MA, after
controlling/adjusting AFS(model 5), or EA, HI(model 2), or EA, AC,
HI(model 3), or EA, SB, HI(model 4) (see Figure 3). Increasing years of
schooling are accompanied by increases AFB (effect of EA on AFB, β=
0.377, 95% CI, 0.344 to 0.409, P = 1.56E-114), so EA may indirectly
have an impact on the risk of MA through AFB (effect of AFB on MA, β=
-0.205, 95% CI, -0.263 to -0.147, P = 5.46E-12) (Supplementary Table
1).By multiplying the estimate of the effect of EA on AFS, AFB with the
estimate of the effect of AFB on MA, the mediation effect of AFB in the
causal pathway from EA to MA was -0.08, accounting for 57.8% of the
total effect (Supplementary Table 2).