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A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations

Heming Wang,Pavithra Nagarajan,Thomas Winkler,Amy Bentley,Clint Miller,Aldi Kraja,Karen Schwander,Songmi Lee,Wenyi Wang,Michael Brown,John Morrison,Ayush Giri,Jeffrey O'Connell,Traci Bartz,Lisa de las Fuentes,Valborg Gudmundsdottir,Xiuqing Guo,Sarah Harris,Zhijie Huang,Mart Kals,Minjung Kho, Christophe Lefevre,Jian'an Luan,Leo-Pekka Lyytikäinen,Massimo Mangino,Y Milaneschi,Nicholette Palmer,Varun Rao,Rainer Rauramaa,Botong Shen,Stefan Stadler,Quan Sun,Jingxian Tang,Sébastien Thériault,Adriaan van der Graaf,Peter van der Most,Yujie Wang,Stefan Weiss,Kenneth Westerman,Qian Yang,Tabara Yasuharu,Wei Zhao,Wanying Zhu,Drew Altschul,Md Abu Yusuf Ansari,Pramod Anugu, Anna Argoty-Pantoja,Michael Arzt,Hugues Aschard,John Attia, Lydia Bazzano, Max Breyer,Jennifer Brody,Brian Cade,Hung-Hsin Chen,Yii-Der Ida Chen,Zekai Chen,Paul de Vries,Latchezar Dimitrov, Ahn Do, Jiawen Du, Charles Dupont,Todd Edwards,Michele Evans,Tariq Faquih,Stephan Felix,Susan Fisher-Hoch,James Floyd,Mariaelisa Graff,C Charles Gu,Dongfeng Gu,Kristen Hairston,Anthony Hanley,Iris Heid,Sami Heikkinen,Heather Highland,Michelle Hood,Mika Kähönen,Carrie Karvonen-Gutierrez,Takahisa Kawaguchi,Setoh Kazuya,Kelly Tanika,Pirjo Komulainen,Daniel Levy,Henry Lin,Peter Liu,Pedro Marques-Vidal,Joseph McCormick,Hao Mei,James Meigs,Cristina Menni,Kisung Nam,Ilja Nolte,Natasha Pacheco,Lauren Petty,Hannah Polikowsky,Michael Province,Bruce Psaty,Laura Raffield,Olli Raitakari,Stephen Rich,Renata Riha,Lorenz Risch,Martin Risch,Edward Ruiz-Narvaez,Rodney Scott,Colleen Sitlani,Jennifer Smith,Tamar Sofer,Maris Teder-Laving,Uwe Völker,Peter Vollenweider,Guanchao Wang,Ko WIllems van Dijk,Otis Wilson,Rui Xia,Jie Yao,Kristin Young,Ruiyuan Zhang,Xiaofeng Zhu,Jennifer Below,Carsten Böger,David Conen,Simon Cox,Marcus Dörr,Mary Feitosa,Ervin Fox,Nora Franceschini,Sina Gharib,Vilmundur Gudnason,Sioban Harlow,Jiang He,Elizabeth Holliday,Zoltan Kutalik,Timo Lakka,Deborah Lawlor,Seunggeun Lee,Terho Lehtimäki,Changwei Li,Ching-Ti Liu,Reedik Mägi,Fumihiko Matsuda,Alanna Morrison,Brenda W J H Penninx,Patricia Peyser,Jerome Rotter,Harold Snieder,T Spector,Lynne Wagenknecht,Nicholas Wareham,Alan Zonderman,Kari North,Myriam Fornage,Adriana Hung,Alisa Manning, W Gauderman,Han Chen,Patricia Munroe,Dabeeru Rao,Diana van Heemst,Susan Redline,Raymond Noordam

Research square(2024)

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Abstract
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 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.
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Key words
Sleep Duration,Sleep Quality
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