Bidirectional two-sample mendelian randomization analysis identifies causal associations between age at menarche and sarcopenia-related traits

Abstract

Background: Observational studies have shown that the age of menarche is associated with sarcopenia, but confounding factors make the causal relationship difficult to infer.

Objective: Therefore, we conducted a bidirectional two-sample Mendelian randomized (MR) analysis to evaluate the potential causal relationship between age at menarche and sarcopenia-related traits (hand grip strength, lean mass, walking pace).

Methods: We obtained the latest aggregate statistics from the Genome-wide association studies (GWAS) database on the age of menarche of 182,416 participants from ReproGen, the appendicular lean mass of 244,730 participants from EMBL's European Bioinformatics Institute, the left-hand grip strength of 401,026 participants, the right-hand grip strength of 461,089 participants and the usual walking pace of 459,915 participants from the UK Biobank. The inverse variance weighting (IVW) method and other MR methods were used to evaluate the bidirectional causal relationship between the age of menarche and sarcopenia.

Results: The forward MR results showed that the age of menarche predicted by the gene was positively correlated with left-hand grip strength (IVW_β=0.041, P = 2.00 × 10^-10), right-hand grip strength (IVW_β=0.053, P = 1.97 × 10^-18), appendicular lean mass (IVW_β=0.012, P = 4.38 × 10^-13) and usual walking pace (IVW_β=0.033, P = 1.62 × 10^-8).In the reverse MR analysis, we also found that the usual walking pace was positively correlated with the age of menarche predicted by genes (IVW_β=0.532, P = 1.65 × 10^-4). Still, there was no causal relationship between grip strength and appendicular lean mass and the age at menarche.

Conclusion: Our results show that earlier menarche will increase the risk of sarcopenia. In addition, people with higher muscle function tend to have menarche later. These findings may provide a reference for prevention strategies and interventions for menarche in advance and sarcopenia.

Keywords: Age at menarche; Grip strength; Lean mass; Mendelian randomization; Sarcopenia; Walking pace.