Bone mineral density (BMD) and lean body mass (LBM) not only have a considerable heritability each, but also are genetically correlated. However, common genetic determinants shared by both traits are largely unknown. In the present study, we performed a bivariate genome-wide association study (GWAS) meta-analysis of hip BMD and trunk lean mass (TLM) in 11,335 subjects from 6 samples, and performed replication in estimated heel BMD and TLM in 215,234 UK Biobank (UKB) participants. We identified 2 loci that nearly attained the genome-wide significance (GWS, p < 5.0 × 10⁻⁸) level in the discovery GWAS meta-analysis and that were successfully replicated in the UKB sample: 11p15.2 (lead SNP rs12800228, discovery p = 2.88 × 10⁻⁷, replication p = 1.95 × 10⁻⁴) and 18q21.32 (rs489693, discovery p = 1.67 × 10⁻⁷, replication p = 1.17 × 10⁻³). The above 2 pleiotropic loci may play a pleiotropic role for hip BMD and TLM development. So our findings provide useful insights that further enhance our understanding of genetic interplay between BMD and LBM.

骨矿物质密度（BMD）和去脂体重（LBM）不仅各自具有相当大的遗传力，而且还具有遗传相关性。然而，这两种性状共有的共同遗传决定因素在很大程度上尚不清楚。在本研究中，我们对来自 6 个样本的 11,335 名受试者的髋部 BMD 和躯干瘦体重 (TLM) 进行了双变量全基因组关联研究 (GWAS) 荟萃分析，并在 215,234 个英国生物库中对估计的脚跟 BMD 和 TLM 进行了复制（英国央行）参与者。我们在发现 GWAS 荟萃分析中确定了 2 个几乎达到全基因组显着性（GWS， p < 5.0 × 10 ^-8 ）水平并且在 UKB 样本中成功复制的基因座：11p15.2（先导 SNP rs12800228，发现p = 2.88 × 10 ^-7 ，复制p = 1.95 × 10 ^-4 ）和18q21.32（rs489693，发现p = 1.67 × 10 ^-7 ，复制p = 1.17 × 10 ^-3 ）。上述2个多效性位点可能对髋部BMD和TLM发育发挥多效性作用。因此，我们的研究结果提供了有用的见解，进一步增强了我们对 BMD 和 LBM 之间遗传相互作用的理解。