孟德尔随机化
全基因组关联研究
特质
遗传关联
遗传建筑学
遗传相关
代谢综合征
观察研究
生物信息学
数量性状位点
生物
医学
遗传学
遗传变异
糖尿病
遗传变异
内科学
单核苷酸多态性
计算机科学
基因
内分泌学
基因型
程序设计语言
作者
Ji-Xiang Huang,Shu-Zhen Xu,Tian Tian,Jing Wang,Ling-Qiong Jiang,Tian He,Shi‐Yin Meng,Jing Ni,Hai‐Feng Pan
标识
DOI:10.1210/clinem/dgae169
摘要
Abstract Context Previous observational studies have indicated a bidirectional association between metabolic syndrome (MetS) and osteoarthritis (OA). However, it remains unclear whether these bidirectional associations reflect causal relationships or shared genetic factors, and the underlying biological mechanisms of this association are not fully understood. Objective We aimed to explore the genetic connection between MetS and OA using genome-wide association study (GWAS) summary data. Methods Leveraging summary statistics from GWAS conducted by the UK Biobank and the Glucose and Insulin-related Traits Consortium (MAGIC), we performed global genetic correlation analyses, genome-wide cross-trait meta-analyses, and a bidirectional two-sample Mendelian randomization analyses using summary statistics from GWAS to comprehensively assess the relationship of MetS and OA. Results We first detected an extensive genetic correlation between MetS and OA (rg = 0.393, P = 1.52 × 10−18), which was consistent in 4 MetS components, including waist circumference, triglycerides, hypertension, and high-density lipoprotein cholesterol and OA with rg ranging from −0.229 to 0.490. We then discovered 32 variants jointly associated with MetS and OA through Multi-Trait Analysis of GWAS (MTAG). Co-localization analysis found 12 genes shared between MetS and OA, with functional implications in several biological pathways. Finally, Mendelian randomization analysis suggested genetic liability to MetS significantly increased the risk of OA, but no reverse causality was found. Conclusion Our results illustrate a common genetic architecture, pleiotropic loci, as well as causality between MetS and OA, potentially enhancing our knowledge of high comorbidity and genetic processes that overlap between the 2 disorders.
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