Age at menarche and cardiovascular risk factors using Mendelian randomization in the Guangzhou Biobank Cohort Study

Observational studies show earlier age at menarche associated with higher risk of cardiovascular disease although these studies could be confounded by childhood obesity or childhood socioeconomic position. We tested the hypothesis that earlier age at menarche is associated with poorer cardiovascular risk factors using a Mendelian randomization design. We conducted a Mendelian randomization study in a large Southern Chinese cohort, the Guangzhou Biobank Cohort Study (n=12,279), to clarify the causal role of menarche in cardiovascular disease risk factors including blood pressure, lipids, fasting glucose, adiposity and type 2 diabetes. A genetic allele score was obtained from single nucleotide polymorphisms associated with age at menarche using stepwise regression and with cross validation. Estimates of the association of age at menarche with cardiovascular disease risk factors were obtained using two stage least squares regression. Height was included as a positive control outcome. The F-statistic for the allele score (rs17268785, rs1859345, rs2090409, rs4452860 and rs4946651) was 19.9. Older age at menarche was associated with lower glucose (-0.39mmol/L per year older menarche, 95% confidence interval (CI) -0.78 to -0.001) but not clearly with any other cardiovascular risk factors. Older age at menarche was also associated with taller height. Age at menarche did not appear to affect cardiovascular disease risk factors except for glucose in an inverse manner. However, these results need to be confirmed in larger Mendelian randomization studies.