Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Soochow University, Suzhou, Jiangsu, PR China.
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou, Jiangsu, PR China.
Eur J Hum Genet. 2021 Apr;29(4):553-563. doi: 10.1038/s41431-020-00727-3. Epub 2020 Sep 22.
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, replication P = 5.75 × 10) at the genome-wide significance level (ɑ = 5.0 × 10), 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两种严重的复杂疾病，威胁着全球公众健康。这两种疾病都受到强烈的遗传决定因素以及遗传相关性的影响。为了确定肥胖症和骨质疏松症的多效基因，我们对来自七个样本的 12981 名参与者的髋部骨矿物质密度（BMD）和全身脂肪量（TBFM）进行了双变量全基因组关联（GWA）荟萃分析，然后在 UK Biobank（UKB）队列样本（N=217822）中进行了计算复现。将发现荟萃分析和复制样本的结果相结合，我们确定了一个新的位点 17q21.31（先导 SNP rs12150327，NC_000017.11：g.44956910G > A，发现双变量 P=4.83×10，复制 P=5.75×10），达到全基因组显著水平（ɑ=5.0×10），该位点可能对髋部 BMD 和 TBFM 具有多效作用。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育具有多效作用。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认识，并为潜在的新疗法提供启示。
