作者
Seyedeh M Zekavat, Shu-Hong Lin, Alexander G Bick, Aoxing Liu, Kaavya Paruchuri, Chen Wang, Md Mesbah Uddin, Yixuan Ye, Zhaolong Yu, Xiaoxi Liu, Yoichiro Kamatani, Romit Bhattacharya, James P Pirruccello, Akhil Pampana, Po-Ru Loh, Puja Kohli, Steven A McCarroll, Krzysztof Kiryluk, Benjamin Neale, Iuliana Ionita-Laza, Eric A Engels, Derek W Brown, Jordan W Smoller, Robert Green, Elizabeth W Karlson, Matthew Lebo, Patrick T Ellinor, Scott T Weiss, Mark J Daly, Chikashi Terao, Hongyu Zhao, Benjamin L Ebert, Muredach P Reilly, Andrea Ganna, Mitchell J Machiela, Giulio Genovese, Pradeep Natarajan
发表日期
2021/6
期刊
Nature Medicine
卷号
27
期号
6
页码范围
1012-1024
出版商
Nature Publishing Group
简介
Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15–1.36; P = 1.8 × 10−7), including sepsis (HR 2.68; 95% CI = 2.25–3.19; P = 3.1 × 10−28), pneumonia (HR 1.76; 95% CI = 1.53–2.03; P = 2.3 × 10−15), digestive …
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