GWAS on hand grip strength: new insights into the genetics of muscular strength support a strong genetic component at different ages

Introduction: Hand grip strength (HGS) is a widespread proxy for muscular strength and a predictor of cardiovascular disease and poor health outcomes. Genetic studies in adult cohorts (e.g. UK Biobank) found multiple genes associated with HGS and showed a modest heritability (h2~24%). However, the genetics of HGS remains largely elusive and has never been explored in a cohort of young individuals. Materials and Methods: We performed GWAS analyses on three measures of HGS in the ALSPAC dataset (N~5,400, mean age = 11.8 years), namely HGS for the right and left hand and grip strength maximal, i.e. best result regardless of the hand used. Analyses were performed in PLINK and functional mapping with FUMA. Genetic correlations and SNP-heritability were computed with LD Score Regression using summary statistics from UK Biobank. Results: We reported a novel genome-wide significant hit for HGS (rs2968991, p < 1.75E-08) with the right hand and we replicated a common association in UK Biobank for the three traits (p < 1E-06). We reported a higher SNP-heritability than previous studies and highlighted a moderate-to-high genetic correlation between HGS in the current study and in the UK Biobank. Conclusions: In addition to a novel association, our analysis replicated some of the associations previously reported both at pathway (skeletal muscle fibres and neurological disorders pathways) and gene-specific (HOXB3) level. This, together with the modest-to-high genetic correlation with HGS in the UK Biobank suggests a stable genetic component of HGS at different ages. This work was funded by the Royal Society.