孟德尔随机化
体质指数
优势比
多效性
置信区间
危险系数
观察研究
生命银行
全基因组关联研究
内科学
荟萃分析
遗传关联
医学
生物
人口学
遗传学
生物信息学
表型
单核苷酸多态性
基因型
基因
遗传变异
社会学
作者
Ling Zhang,Wei Zhang,Xuan Wu,Huanxian Cui,Yan Peng,Chunxia Yang,Xinyi Zhao,Jinyu Xiao,Cui Xiao,Min Tang,Yajun Wang,Lidong Chen,Yi Liu,Yi Zou,Ling Zhang,Yang Yao,Yang Yao,Jia Li,Fei Liu,Chunxia Yang,Bo Zhang,Xiaojuan Jiang
标识
DOI:10.1016/j.joca.2023.02.073
摘要
Objective We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites. Method We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner. Results Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37–1.39). A positive overall genetic correlation was observed for BMI and OA ( r g = 0.43, P = 4.72 × 10−133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene–tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42–1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee. Conclusion Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.
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