PDF(Pubmed)
Abstract：
Body composition (fat, skeletal muscle and bone mass) is an important determinant of overall health and risk of endocrine disorders such as type 2 diabetes and osteoporosis. Although diet and physical activity are strongly implicated, body composition is also heritable. We conducted a discovery genome-wide association study on 31 phenotypes from the three-compartment body composition model (fat, lean and bone mass) in a set of 4 386 individuals (n = 2 109 males, n = 2 294 females) from the UK Biobank pilot imaging enhancement program that underwent a dual energy X-ray absorptiometry (DXA) scan for assessment of body composition and genetic screening. From 6 137 607 imputed single nucleotide polymorphisms (SNPs) we identified 17 body composition loci (P<5.0 x 10-8). GWAS from the combined dataset identified four statistically significant SNPs (rs7592270, rs145972737, rs13212044, rs77772562). In sex-stratified GWAS, 10 male specific SNPs across all traits were identified and five female specific SNPs. Of the 17 SNPs, six were in or close to a gene where there was a plausible functional connection. Three SNPs (rs7592270, rs77772562 and rs7552312) were correlated with obesity phenotypes, one SNP (rs2236705) with lean phenotypes and two with bone mass phenotypes (rs112098641 and rs113380185). These results highlight candidate genes and biological pathways related to body composition, including glucose metabolism and estrogen regulation, that are of interest to replicate in future studies.
摘要：
身体成分（脂肪，骨骼肌和骨量）是整体健康和内分泌失调风险的重要决定因素，例如2型糖尿病和骨质疏松症。虽然饮食和身体活动有很强的牵连，身体成分也是可遗传的。我们对来自三室身体成分模型的31种表型（脂肪，瘦和骨量)在一组4386人(n=2109名男性，n=2294名女性）来自UKBiobank飞行员成像增强计划，该计划进行了双能量X射线吸收法（DXA）扫描，以评估身体成分和遗传筛查。从6137607个估算的单核苷酸多态性（SNP）中，我们鉴定了17个身体组成基因座（P<5.0x10-8）。来自组合数据集的GWAS鉴定了四个统计上显著的SNP(rs7592270、rs145972737、rs13212044、rs77772562)。在性别分层的GWAS中，鉴定了所有性状中的10个雄性特异性SNP和5个雌性特异性SNP。在17个SNP中，其中有6个在一个基因中或接近一个基因，在这个基因中存在一种看似合理的功能联系。三个SNP(rs7592270、rs77772562和rs7552312)与肥胖表型相关,一个SNP（rs2236705）具有瘦表型，两个具有骨量表型（rs112098641和rs113380185）。这些结果突出了与身体组成相关的候选基因和生物学途径，包括葡萄糖代谢和雌激素调节，在未来的研究中有兴趣复制。
