Ran Shu, Lin XiTong, Wang SiQi, Li ZhuoQi, Liu BaoLin
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
Calcif Tissue Int. 2025 Jan 3;116(1):10. doi: 10.1007/s00223-024-01312-2.
This study aims to identify novel loci associated with sarcopenia-related traits in UK Biobank (UKB) through multi-trait genome-wide analysis. To identify novel loci associated with sarcopenia, we integrated the genome-wide association studies (GWAS) of usual walking pace (UWP) and hand grip strength (HGS) to conduct a joint association study known as multi-trait analysis of GWAS (MTAG). We performed a transcriptome-wide association study (TWAS) to analyze the results of MTAG in relation to mRNA expression data for genes identified in skeletal muscle. Additionally, we utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to explore the relationships between the identified genes and hub genes related to sarcopenia. We identified 15 novel loci associated with UWP and 5 novel loci associated with HGS at the genome wide significance level (GWS, ). After TWAS ( ), we found two significant genes: PPP1R3A, located at 7q31.1 and associated with HGS, and ZBTB38, located at 3q23 and associated with UWP. 11 identified genes associated with hub genes for sarcopenia were obtained through WGCNA. Our findings offer new insights into biological mechanisms underlying sarcopenia and identify several novel genes related to sarcopenia that warrant in-depth study.
本研究旨在通过多性状全基因组分析，在英国生物银行（UKB）中识别与肌肉减少症相关性状相关的新基因座。为了识别与肌肉减少症相关的新基因座，我们整合了日常步行速度（UWP）和握力（HGS）的全基因组关联研究（GWAS），以进行一项名为GWAS多性状分析（MTAG）的联合关联研究。我们进行了全转录组关联研究（TWAS），以分析MTAG结果与骨骼肌中鉴定出的基因的mRNA表达数据之间的关系。此外，我们利用加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络，探索鉴定出的基因与肌肉减少症相关的枢纽基因之间的关系。我们在全基因组显著性水平（GWS， ）下鉴定出15个与UWP相关的新基因座和5个与HGS相关的新基因座。经过TWAS（ ）后，我们发现了两个显著基因：位于7q31.1且与HGS相关的PPP1R3A，以及位于3q23且与UWP相关的ZBTB38。通过WGCNA获得了11个与肌肉减少症枢纽基因相关的鉴定基因。我们的研究结果为肌肉减少症的生物学机制提供了新的见解，并鉴定出了几个与肌肉减少症相关的新基因，值得深入研究。
