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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).

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