A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations
Author:
Nagarajan PavithraORCID, Winkler Thomas WORCID, Bentley Amy RORCID, Miller Clint LORCID, Kraja Aldi T, Schwander Karen, Lee Songmi, Wang Wenyi, Brown Michael R, Morrison John L, Giri AyushORCID, O’Connell Jeffrey R, Bartz Traci M, de las Fuentes LisaORCID, Gudmundsdottir ValborgORCID, Guo Xiuqing, Harris Sarah E, Huang Zhijie, Kals Mart, Kho Minjung, Lefevre Christophe, Luan Jian’an, Lyytikäinen Leo-PekkaORCID, Mangino MassimoORCID, Milaneschi YuriORCID, Palmer Nicholette D, Rao Varun, Rauramaa Rainer, Shen Botong, Stadler Stefan, Sun Quan, Tang Jingxian, Thériault SébastienORCID, van der Graaf Adriaan, van der Most Peter J, Wang Yujie, Weiss Stefan, Westerman Kenneth EORCID, Yang Qian, Yasuharu Tabara, Zhao Wei, Zhu Wanying, Altschul Drew, Ansari Md Abu Yusuf, Anugu Pramod, Argoty-Pantoja Anna D, Arzt Michael, Aschard HuguesORCID, Attia John R, Bazzanno Lydia, Breyer Max A, Brody Jennifer A, Cade Brian EORCID, Chen Hung-hsin, Chen Yii-Der Ida, Chen Zekai, de Vries Paul S, Dimitrov Latchezar M, Do Anh, Du Jiawen, Dupont Charles T, Edwards Todd L, Evans Michele K, Faquih Tariq, Felix Stephan B, Fisher-Hoch Susan P, Floyd James S, Graff Mariaelisa, Gu Charles, Gu Dongfeng, Hairston Kristen G, Hanley Anthony J, Heid Iris M, Heikkinen Sami, Highland Heather M, Hood Michelle M, Kähönen Mika, Karvonen-Gutierrez Carrie A, Kawaguchi TakahisaORCID, Kazuya Setoh, Kelly Tanika NORCID, Komulainen Pirjo, Levy Daniel, Lin Henry J, Liu Peter Y, Marques-Vidal Pedro, McCormick Joseph BORCID, Mei Hao, Meigs James B, Menni Cristina, Nam Kisung, Nolte Ilja M, Pacheco Natasha L, Petty Lauren E, Polikowsky Hannah G, Province Michael A, Psaty Bruce M, Raffield Laura M, Raitakari Olli TORCID, Rich Stephen S, Riha Renata LORCID, Risch LorenzORCID, Risch Martin, Ruiz-Narvaez Edward A, Scott Rodney JORCID, Sitlani Colleen MORCID, Smith Jennifer A, Sofer TamarORCID, Teder-Laving Maris, Völker Uwe, Vollenweider Peter, Wang Guanchao, Dijk Ko Willems van, Wilson Otis D, Xia Rui, Yao Jie, Young Kristin L, Zhang Ruiyuan, Zhu Xiaofeng, Below Jennifer E, Böger Carsten A, Conen David, Cox Simon RORCID, Dörr Marcus, Feitosa Mary FORCID, Fox Ervin R, Franceschini NoraORCID, Gharib Sina AORCID, Gudnason VilmundurORCID, Harlow Sioban D, He Jiang, Holliday Elizabeth G, Kutalik Zoltan, Lakka Timo AORCID, Lawlor Deborah A, Lee SeunggeunORCID, Lehtimäki Terho, Li ChangweiORCID, Liu Ching-Ti, Mägi ReedikORCID, Matsuda Fumihiko, Morrison Alanna C, Penninx Brenda WJHORCID, Peyser Patricia A, Rotter Jerome IORCID, Snieder Harold, Spector Tim D, Wagenknecht Lynne E, Wareham Nicholas JORCID, Zonderman Alan B, North Kari EORCID, Fornage Myriam, , Hung Adriana M, Manning Alisa K, Gauderman JamesORCID, Chen Han, Munroe Patricia BORCID, Rao Dabeeru C, van Heemst Diana, Redline Susan, Noordam RaymondORCID, Wang Heming
Abstract
ABSTRACTAlthough both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.
Publisher
Cold Spring Harbor Laboratory
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