Estimation of Causal Effect of Age at Menarche on Pubertal Height Growth Using Mendelian Randomization.

We use Mendelian randomization to estimate the causal effect of age at menarche on late pubertal height growth and total pubertal height growth. The instrument SNPs selected from the exposure genome-wide association study (GWAS) are validated in additional population-matched exposure GWASs. Based on the inverse variance weighting method, there is a positive causal relationship of age at menarche on late pubertal growth (β^=0.56, 95% CI: (0.34, 0.78), p=3.16×10-7) and on total pubertal growth (β^=0.36, 95% CI: (0.14, 0.58), p=1.30×10-3). If the instrument SNPs are not validated in additional exposure GWASs, the estimated effect on late pubertal height growth increases by 3.6% to β^=0.58 (95% CI: (0.42, 0.73), p=4.38×10-13) while the estimates on total pubertal height growth increases by 41.7% to β^=0.51 (95% CI: (0.35, 0.67), p=2.96×10-11).