Associations between age at menarche and risk of heart failure: a genetic correlation and mendelian randomization study.

Objective To investigate the correlation and causation between age at menarche (AAM) and risk of heart failure (HF) with genetic correlation analysis and Mendelian randomization (MR). Methods Based on genome - wide association study (GWAS) data on age at menarche and heart failure, genetic correlation was assessed using linkage disequilibrium regression (LDSC) and Genomic structural equation models (Genomic SEM). Univariate MR and multivariate MR were used to explore the total and direct effects of age at menarche on heart failure risk respectively. Results There was a negative genetic correlation between AAM and HF (rg = -0. 271, P = 1. 94 X 10-9). After additionally adjusting for confounders, genomic SEM analysis revealed a negative partial correlation between AAM and HF. Univariable MR results showed that genetically predicated AAM and HF risk had a negative causal effect (IVW: OR =0.884; 95% CI: 0.854 -0.916, P < 0. 001), and multivariable MR results showed that the negative causal association remained after adjusting for confounders. Conclusion This study suggests that genetically predicted early age at menarche increases the risk of heart failure. [ABSTRACT FROM AUTHOR]