Papadopoulou A, Litkowski E M, Graff M, Wang Z, Smit R A J, Chittoor G, Dinsmore I, Josyula N S, Lin M, Shortt J, Zhu W, Vedantam S L, Yengo L, Wood A R, Berndt S I, Holm I A, Mentch F D, Hakonarson H, Kiryluk K, Weng C, Jarvik G P, Crosslin D, Carrell D, Kullo I J, Dikilitas O, Hayes M G, Wei W -Q, Edwards D R V, Assimes T L, Hirschhorn J N, Below J E, Gignoux C R, Justice A E, Loos R J F, Sun Y V, Raghavan S, Deloukas P, North K E, Marouli E
William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
VA Eastern Colorado Health Care System, Aurora, CO, USA.
NPJ Genom Med. 2025 Feb 27;10(1):14. doi: 10.1038/s41525-025-00464-w.
We performed ancestry and sex specific Phenome Wide Association Studies (PheWAS) to explore disease related outcomes associated with genetically predicted height. This is the largest PheWAS on genetically predicted height involving up to 840,000 individuals of diverse ancestry. We explored European, African, East Asian ancestries and Hispanic population groups. Increased genetically predicted height is associated with hyperpotassemia and autism in the male cross-ancestry analysis. We report male-only European ancestry associations with anxiety disorders, post-traumatic stress and substance addiction and disorders. We identify a signal with benign neoplasm of other parts of digestive system in females. We report associations with a series of disorders, several with no prior evidence of association with height, involving mental disorders and the endocrine system. Our study suggests that increased genetically predicted height is associated with higher prevalence of many clinically relevant traits which has important implications for epidemiological and clinical disease surveillance and risk stratification.
我们开展了按血统和性别分类的全表型组关联研究(PheWAS),以探究与基因预测身高相关的疾病相关结局。这是针对基因预测身高开展的最大规模的PheWAS,涉及多达840,000名不同血统的个体。我们研究了欧洲、非洲、东亚血统群体以及西班牙裔人群。在男性跨血统分析中,基因预测身高增加与高钾血症和自闭症相关。我们报告了仅在欧洲血统男性中,身高与焦虑症、创伤后应激障碍及物质成瘾和障碍之间的关联。我们在女性中发现了与消化系统其他部位良性肿瘤相关的信号。我们报告了身高与一系列疾病的关联,其中一些疾病此前并无与身高相关的证据,这些疾病涉及精神障碍和内分泌系统。我们的研究表明,基因预测身高增加与许多临床相关特征的较高患病率相关,这对流行病学和临床疾病监测以及风险分层具有重要意义。