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 discovered 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.

© 2025. The Author(s), under exclusive licence to Springer Nature Limited.

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TitleA large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations.
DateApril 4th, 2025
Issue nameMolecular psychiatry
Issue numberpubmed:40181193
DOI10.1038/s41380-025-02954-w
PubMed40181193
AuthorsNagarajan P, Winkler TW, Bentley AR, Miller CL, Kraja AT, Schwander K, Lee S, Wang W, Brown MR, Morrison JL, Giri A, O'Connell JR, Bartz TM, de Las Fuentes L, Gudmundsdottir V, Guo X, Harris SE, Huang Z, Kals M, Kho M, Lefevre C, Luan J, Lyytikäinen LP, Mangino M, Milaneschi Y, Palmer ND, Rao V, Rauramaa R, Shen B, Stadler S, Sun Q, Tang J, Thériault S, van der Graaf A, van der Most PJ, Wang Y, Weiss S, Westerman KE, Yang Q, Yasuharu T, Zhao W, Zhu W, Altschul D, Ansari MAY, Anugu P, Argoty-Pantoja AD, Arzt M, Aschard H, Attia JR, Bazzanno L, Breyer MA, Brody JA, Cade BE, Chen HH, Chen YI, Chen Z, de Vries PS, Dimitrov LM, Do A, Du J, Dupont CT, Edwards TL, Evans MK, Faquih T, Felix SB, Fisher-Hoch SP, Floyd JS, Graff M, Gu C, Gu D, Hairston KG, Hanley AJ, Heid IM, Heikkinen S, Highland HM, Hood MM, Kähönen M, Karvonen-Gutierrez CA, Kawaguchi T, Kazuya S, Kelly TN, Komulainen P, Levy D, Lin HJ, Liu PY, Marques-Vidal P, McCormick JB, Mei H, Meigs JB, Menni C, Nam K, Nolte IM, Pacheco NL, Petty LE, Polikowsky HG, Province MA, Psaty BM, Raffield LM, Raitakari OT, Rich SS, Riha RL, Risch L, Risch M, Ruiz-Narvaez EA, Scott RJ, Sitlani CM, Smith JA, Sofer T, Teder-Laving M, Völker U, Vollenweider P, Wang G, Willems van Dijk K, Wilson OD, Xia R, Yao J, Young KL, Zhang R, Zhu X, Below JE, Böger CA, Conen D, Cox SR, Dörr M, Feitosa MF, Fox ER, Franceschini N, Gharib SA, Gudnason V, Harlow SD, He J, Holliday EG, Kutalik Z, Lakka TA, Lawlor DA, Lee S, Lehtimäki T, Li C, Liu CT, Mägi R, Matsuda F, Morrison AC, Penninx BW, Peyser PA, Rotter JI, Snieder H, Spector TD, Wagenknecht LE, Wareham NJ, Zonderman AB, North KE, Fornage M, Hung AM, Manning AK, Gauderman J, Chen H, Munroe PB, Rao DC, van Heemst D, Redline S, Noordam R & Wang H
InfoMillion Veteran Program, Muralidhar S, Moser J, Deen JE, Tsao PS, Gaziano JM, Hauser E, Kilbourne A, Matheny M, Oslin D, Churby L, Whitbourne SB, Brewer JV, Shayan SA, Selva LE, Pyarajan S, Cho K, DuVall SL, Brophy MT, Stephens B, Connor T, Argyres DP, Assimes TL, Hung A, Kranzler H, Aguayo S, Ahuja S, Alexander K, Androulakis XM, Balasubramanian P, Ballas Z, Bast ES, Beckham J, Bhushan S, Boyko E, Cohen D, Dellitalia L, Dryden GW, Faulk LC, Fayad J, Fujii D, Gappy S, Gesek F, Greco J, Godschalk M, Gress TW, Gupta S, Gutierrez S, Harley J, Hamner M, Hogan DJ, Hurley R, Iruvanti P, Jacono F, Jhala D, Kinlay S, Landry M, Liang P, Liangpunsakul S, Lichy J, Lo TS, Mahan CS, Marrache R, Mastorides S, Mattocks K, Meyer P, Moorman J, Morales P, Morgan T, Murdoch M, Naik E, Norton J, Okusaga O, Ong MK, Oursler KA, Petrakis I, Poon S, Potter E, Rauchman M, Rai AS, Servatius R, Sharma S, Smith R, Sriram P, Strollo P, Tandon N, Villareal G, Walsh J, Wells J, Whittle J, Whooley M, Wilson P, Xu J, Yeh SS, Yen AW
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