Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts

Abstract Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10, NUDT3, NCF2, SMG7, and ARPC5, were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the ‘mRNA destabilisation’ biological process was enriched for sarcopenia. Our study identified RPS10, NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia.