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.
Highlights
Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass
No significant difference was observed in mean height (1.59 ± 0.08 m in Veterans Health Service Medical Center (VHSMC) vs 1.59 ± 0.09 m in Korean Association Resource (KARE), P = 1.000) between the two cohorts
The mean values of skeletal muscle index (SMI) and appendicular skeletal muscle mass (ASM), which could only be calculated for the VHSMC cohort, were 6.77 ± 1.00 kg/m2 and 17.49 ± 4.06 kg, respectively
Summary
Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. The Asian working group for sarcopenia 2019 (AWGS 2019) recently reached the consensus that skeletal muscle index (SMI) and appendicular skeletal muscle (ASM) may be reliable p arameters[11] In this respect, in addition to LBM, it is necessary to analyse SMI and ASM to understand the complex aetiology of sarcopenia, Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Providing fewer biological insights into pathways regarding s arcopenia[20] To address this issue, a large GWAS metaanalysis was conducted using 20 cohorts of European ancestry, identifying a set of five loci (HSD17B11, VCAN, ADAMTSL3, IRS1 and FTO) for total LBM, and SNPs related to IRS1, ADAMTSL3, and VCAN for appendicular LBM22. The current study conducted a GWAS meta-analysis on sarcopenia phenotypes using Korean relatively aged cohorts, combining the Veterans Health Service Medical Center (VHSMC) and Korean Association Resource (KARE) cohorts
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