Dataset Information

Association of 3p27.1 Variants with Whole Body Lean Mass Identified by a Genome-wide Association Study.

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.

SUBMITTER: Ran S

PROVIDER: S-EPMC7062907 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Association of 3p27.1 Variants with Whole Body Lean Mass Identified by a Genome-wide Association Study.

Ran Shu S Zhang Yu-Xue YX Liu Lu L Jiang Zi-Xuan ZX He Xiao X Liu Yu Y Shen Hui H Tian Qing Q Pei Yu-Fang YF Deng Hong-Wen HW Zhang Lei L

Scientific reports 20200309 1

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<sup>-8</sup>) in the discovery FHS sample, and the lead SNP was successfully replicated in the KCOS ...[more]

PMID: 32152362

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Project description:Bone and muscle, two major tissue types of musculoskeletal system, have strong genetic determination. Abnormality in bone and/or muscle may cause musculoskeletal diseases such as osteoporosis and sarcopenia. Bone size phenotypes (BSPs), such as hip bone size (HBS), appendicular bone size (ABS), are genetically correlated with body lean mass (mainly muscle mass). However, the specific genes shared by these phenotypes are largely unknown. In this study, we aimed to identify the specific genes with pleiotropic effects on BSPs and appendicular lean mass (ALM). We performed a bivariate genome-wide association study (GWAS) by analyzing ~690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) followed by a replication study in 2,286 unrelated US Caucasians (558 males and 1,728 females). We identified 14 interesting single nucleotide polymorphisms (SNPs) that may contribute to variation of both BSPs and ALM, with p values <10(-6) in discovery stage. Among them, the association of three SNPs (rs2507838, rs7116722, and rs11826261) in/near GLYAT (glycine-N-acyltransferase) gene was replicated in US Caucasians, with p values ranging from 1.89 × 10(-3) to 3.71 × 10(-4) for ALM-ABS, from 5.14 × 10(-3) to 1.11 × 10(-2) for ALM-HBS, respectively. Meta-analyses yielded stronger association signals for rs2507838, rs7116722, and rs11826261, with pooled p values of 1.68 × 10(-8), 7.94 × 10(-8), 6.80 × 10(-8) for ALB-ABS and 1.22 × 10(-4), 9.85 × 10(-5), 3.96 × 10(-4) for ALM-HBS, respectively. Haplotype allele ATA based on these three SNPs was also associated with ALM-HBS and ALM-ABS in both discovery and replication samples. Interestingly, GLYAT was previously found to be essential to glucose metabolism and energy metabolism, suggesting the gene's dual role in both bone development and muscle growth. Our findings, together with the prior biological evidence, suggest the importance of GLYAT gene in co-regulation of bone phenotypes and body lean mass.

Dataset Information

Association of 3p27.1 Variants with Whole Body Lean Mass Identified by a Genome-wide Association Study.

Publications

Association of 3p27.1 Variants with Whole Body Lean Mass Identified by a Genome-wide Association Study.

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