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.
A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations / P. Nagarajan, T.W. Winkler, A.R. Bentley, C.L. Miller, A.T. Kraja, K. Schwander, S. Lee, W. Wang, M.R. Brown, J.L. Morrison, A. Giri, J.R. O'Connell, T.M. Bartz, L. De Las Fuentes, V. Gudmundsdottir, X. Guo, S.E. Harris, Z. Huang, M. Kals, M. Kho, C. Lefevre, J. Luan, L. Lyytikäinen, M. Mangino, Y. Milaneschi, N.D. Palmer, V. Rao, R. Rauramaa, B. Shen, S. Stadler, Q. Sun, J. Tang, S. Thériault, A. Van Der Graaf, P.J. Van Der Most, Y. Wang, S. Weiss, K.E. Westerman, Q. Yang, T. Yasuharu, W. Zhao, W. Zhu, D. Altschul, M.A.Y. Ansari, P. Anugu, A.D. Argoty-Pantoja, M. Arzt, H. Aschard, J.R. Attia, L. Bazzanno, M.A. Breyer, J.A. Brody, B.E. Cade, H. Chen, Y.I. Chen, Z. Chen, P.S. De Vries, L.M. Dimitrov, A. Do, J. Du, C.T. Dupont, T.L. Edwards, M.K. Evans, T. Faquih, S.B. Felix, S.P. Fisher-Hoch, J.S. Floyd, M. Graff, C. Gu, D. Gu, K.G. Hairston, A.J. Hanley, I.M. Heid, S. Heikkinen, H.M. Highland, M.M. Hood, M. Kähönen, C.A. Karvonen-Gutierrez, T. Kawaguchi, S. Kazuya, T.N. Kelly, P. Komulainen, D. Levy, H.J. Lin, P.Y. Liu, P. Marques-Vidal, J.B. Mccormick, H. Mei, J.B. Meigs, C. Menni, K. Nam, I.M. Nolte, N.L. Pacheco, L.E. Petty, H.G. Polikowsky, M.A. Province, B.M. Psaty, L.M. Raffield, O.T. Raitakari, S.S. Rich, R.L. Riha, L. Risch, M. Risch, E.A. Ruiz-Narvaez, R.J. Scott, C.M. Sitlani, J.A. Smith, T. Sofer, M. Teder-Laving, U. Völker, P. Vollenweider, G. Wang, K. Willems Van Dijk, O.D. Wilson, R. Xia, J. Yao, K.L. Young, R. Zhang, X. Zhu, J.E. Below, C.A. Böger, D. Conen, S.R. Cox, M. Dörr, M.F. Feitosa, E.R. Fox, N. Franceschini, S.A. Gharib, V. Gudnason, S.D. Harlow, J. He, E.G. Holliday, Z. Kutalik, T.A. Lakka, D.A. Lawlor, S. Lee, T. Lehtimäki, C. Li, C. Liu, R. Mägi, F. Matsuda, A.C. Morrison, B.W. Penninx, P.A. Peyser, J.I. Rotter, H. Snieder, T.D. Spector, L.E. Wagenknecht, N.J. Wareham, A.B. Zonderman, K.E. North, M. Fornage, A.M. Hung, A.K. Manning, J. Gauderman, H. Chen, P.B. Munroe, D.C. Rao, D. Van Heemst, S. Redline, R. Noordam, H. Wang. - In: MOLECULAR PSYCHIATRY. - ISSN 1476-5578. - 30:8(2025 Aug), pp. 3660-3672. [10.1038/s41380-025-02954-w]
A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations
C. Menni;
2025
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 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.
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