Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 199 Ren-ai Rd.Jiangsu, Suzhou, 215123, People's Republic of China.
School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
Mol Genet Genomics. 2021 Jan;296(1):55-65. doi: 10.1007/s00438-020-01724-3. Epub 2020 Sep 24.
Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10, replication p = 1.03 × 10), 16q12.2 (rs1421085, discovery p = 2.04 × 10, replication p = 6.47 × 10) and 18q21.32 (rs11152213, discovery p = 3.47 × 10, replication p = 6.69 × 10). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.
骨密度（BMD）和瘦体重（LBM）都是重要的生理指标，具有很强的遗传决定因素。此外，BMD 和 LBM 可能具有共同的遗传因素。为了确定与 BMD 和 LBM 相关的多效性基因组座，我们对股骨颈骨密度和手臂和腿部的 LBM 进行了双变量全基因组关联研究荟萃分析，并在大型英国生物库队列样本中进行了复制。将发现荟萃分析和复制样本的结果结合起来，我们在全基因组显著水平（p < 5.0 × 10）鉴定了三个基因组座：2p23.2（先导 SNP rs4477866，发现 p = 3.47 × 10，复制 p = 1.03 × 10），16q12.2（rs1421085，发现 p = 2.04 × 10，复制 p = 6.47 × 10）和 18q21.32（rs11152213，发现 p = 3.47 × 10，复制 p = 6.69 × 10）。我们的研究结果不仅为瘦体重和骨量发育提供了有用的见解，而且增强了我们对 BMD 和 LBM 之间潜在遗传相关性的理解。
