Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, NC_000017.11:g.44956910G > A, discovery bivariate P = 4.83 × 10⁻⁹, replication P = 5.75 × 10⁻⁵) at the genome-wide significance level (ɑ = 5.0 × 10⁻⁸), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.

骨质疏松症和肥胖症是威胁全球公共卫生的两种严重的复杂疾病。这两种疾病都受到强大的遗传决定因素以及遗传相关性的影响。为了识别肥胖和骨质疏松症的多效性基因，我们对来自 7 个样本的 12,981 名参与者的髋骨矿物质密度 (BMD) 和总体脂肪量 (TBFM) 进行了双变量全基因组关联 (GWA) 荟萃分析，然后在英国生物银行 (UKB) 队列样本中进行计算机复制 ( N  = 217,822)。结合发现元分析和复制样本的结果，我们确定了一个新基因座，17q21.31（前导 SNP rs12150327，NC_000017.11:g.44956910G > A，发现双变量P  = 4.83 × 10 ^{- 9}，复制P = 5.75 × 10 ^{- 5} ）在全基因组显着性水平（ɑ  = 5.0 × 10 ^-8），这可能对髋关节 BMD 和 TBFM 都有多效性影响。功能注释突出了几个候选基因，包括KIF18B、C1QL1和PRPF19，它们可能对体重和骨量的发展产生多效性影响。我们的研究结果可以提高我们对骨质疏松症和肥胖症病因的理解，并阐明潜在的新疗法。