PDF(Pubmed)
Abstract：
Whole body lean mass (WBLM) is a heritable trait predicting sarcopenia. To identify genomic locus underlying WBLM, we performed a genome-wide association study of fat-adjusted WBLM in the Framingham Heart Study (FHS, N = 6,004), and replicated in the Kansas City Osteoporosis Study (KCOS, N = 2,207). We identified a novel locus 3p27.1 that was associated with WBLM (lead SNP rs3732593 P = 7.19 × 10-8) in the discovery FHS sample, and the lead SNP was successfully replicated in the KCOS sample (one-sided P = 0.04). Bioinformatics analysis found that this SNP and its adjacent SNPs had the function of regulating enhancer activity in skeletal muscle myoblasts cells, further confirming the regulation of WBLM by this locus. Our finding provides new insight into the genetics of WBLM and enhance our understanding of sarcopenia.
摘要：
全身瘦体重（WBLM）是预测肌肉减少症的遗传性状。为了确定WBLM背后的基因组基因座，我们在弗雷明汉心脏研究中进行了脂肪调整WBLM的全基因组关联研究(FHS，N=6,004)，并在堪萨斯城骨质疏松症研究(KCOS，N=2,207）。我们在发现的FHS样本中发现了与WBLM（前导SNPrs3732593P=7.19×10-8）相关的新基因座3p27.1，并且前导SNP在KCOS样品中成功复制(单侧P=0.04)。生物信息学分析发现,该SNP及其邻近SNP具有调节骨骼肌成肌细胞增强子活性的功能,进一步证实了该基因座对WBLM的调节。我们的发现为WBLM的遗传学提供了新的见解，并增强了我们对肌少症的理解。
