Association of 3p27.1 Variants with Whole Body Lean Mass Identified by a Genome-wide Association Study.
Shu RanYu-Xue ZhangLu LiuZi-Xuan JiangXiao HeYu LiuHui ShenQing TianYu-Fang PeiHong-Wen DengLei ZhangPublished in: Scientific reports (2020)
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.
Keyphrases
- genome wide association study
- skeletal muscle
- genome wide
- copy number
- bone mineral density
- induced apoptosis
- small molecule
- heart failure
- bioinformatics analysis
- postmenopausal women
- insulin resistance
- oxidative stress
- gene expression
- fatty acid
- metabolic syndrome
- high throughput
- body composition
- binding protein
- cell cycle arrest
- endoplasmic reticulum stress