Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height.

IF 4.7 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2025-02-27 DOI:10.1038/s41525-025-00464-w

A Papadopoulou, E M Litkowski, M Graff, Z Wang, R A J Smit, G Chittoor, I Dinsmore, N S Josyula, M Lin, J Shortt, W Zhu, S L Vedantam, L Yengo, A R Wood, S I Berndt, I A Holm, F D Mentch, H Hakonarson, K Kiryluk, C Weng, G P Jarvik, D Crosslin, D Carrell, I J Kullo, O Dikilitas, M G Hayes, W -Q Wei, D R V Edwards, T L Assimes, J N Hirschhorn, J E Below, C R Gignoux, A E Justice, R J F Loos, Y V Sun, S Raghavan, P Deloukas, K E North, E Marouli

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Abstract

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.

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我们进行了针对不同祖先和性别的表型组广泛关联研究（Phenome Wide Association Studies，PheWAS），以探索与遗传预测身高相关的疾病相关结果。这是关于遗传预测身高的最大规模 PheWAS，涉及多达 840,000 名不同血统的个体。我们研究了欧洲、非洲、东亚和西班牙裔人群。在男性跨血统分析中，遗传预测身高的增加与高地中海贫血症和自闭症有关。我们报告了男性欧洲血统与焦虑症、创伤后应激反应、药物成瘾和失调的关联。我们发现了女性消化系统其他部位良性肿瘤的信号。我们报告了与一系列疾病的关联，其中一些疾病以前没有证据表明与身高有关，涉及精神障碍和内分泌系统。我们的研究表明，遗传预测身高的增加与许多临床相关特征的高患病率有关，这对流行病学和临床疾病监测及风险分层具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.