A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations
Authors: Nagarajan Pavithra , Winkler Thomas W , Bentley Amy R , Miller Clint L , Kraja Aldi T , Schwander Karen , Lee Songmi , Wang Wenyi , Brown Michael R , Morrison John L , Giri Ayush , O’Connell Jeffrey R , Bartz Traci M , de las Fuentes Lisa , Gudmundsdottir Valborg , Guo Xiuqing , Harris Sarah E , Huang Zhijie , Kals Mart , Kho Minjung , Lefevre Christophe , Luan Jian’an , Lyytikäinen Leo-Pekka , Mangino Massimo , Milaneschi Yuri , Palmer Nicholette D , Rao Varun , Rauramaa Rainer , Shen Botong , Stadler Stefan , Sun Quan , Tang Jingxian , Thériault Sébastien , van der Graaf Adriaan , van der Most Peter J , Wang Yujie , Weiss Stefan , Westerman Kenneth E , Yang Qian , Yasuharu Tabara , Zhao Wei , Zhu Wanying , Altschul Drew , Ansari Md Abu Yusuf , Anugu Pramod , Argoty-Pantoja Anna D , Arzt Michael , Aschard Hugues , Attia John R , Bazzanno Lydia , Breyer Max A , Brody Jennifer A , Cade Brian E , 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 Takahisa , Kazuya Setoh , Kelly Tanika N , Komulainen Pirjo , Levy Daniel , Lin Henry J , Liu Peter Y , Marques-Vidal Pedro , McCormick Joseph B , 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 T , Rich Stephen S , Riha Renata L , Risch Lorenz , Risch Martin , Ruiz-Narvaez Edward A , Scott Rodney J , Sitlani Colleen M , Smith Jennifer A , Sofer Tamar , 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 R , Dörr Marcus , Feitosa Mary F , Fox Ervin R , Franceschini Nora , Gharib Sina A , Gudnason Vilmundur , Harlow Sioban D , He Jiang , Holliday Elizabeth G , Kutalik Zoltan , Lakka Timo A , Lawlor Deborah A , Lee Seunggeun , Lehtimäki Terho , Li Changwei , Liu Ching-Ti , Mägi Reedik , Matsuda Fumihiko , Morrison Alanna C , Penninx Brenda WJH , Peyser Patricia A , Rotter Jerome I , Snieder Harold , Spector Tim D , Wagenknecht Lynne E , Wareham Nicholas J , Zonderman Alan B , North Kari E , Fornage Myriam ,   Million Veteran Program, Hung Adriana M , Manning Alisa K , Gauderman James , Chen Han , Munroe Patricia B , Rao Dabeeru C , van Heemst Diana , Redline Susan , Noordam Raymond , Wang Heming 
Published: March 2024

Although 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.