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Wang, H.* ; Noordam, R.* ; Cade, B.E.* ; Schwander, K.* ; Winkler, T.W.* ; Lee, J.* ; Sung, Y.J.* ; Bentley, A.R.* ; Manning, A.K.* ; Aschard, H.* ; Kilpeläinen, T.O.* ; Ilkov, M.* ; Brown, M.R.* ; Horimoto, A.R.* ; Richard, M.* ; Bartz, T.M.* ; Vojinovic, D.* ; Lim, E.* ; Nierenberg, J.L.* ; Liu, Y.* ; Chitrala, K.* ; Rankinen, T.* ; Musani, S.K.* ; Franceschini, N.* ; Rauramaa, R.* ; Alver, M.* ; Zee, P.C.* ; Harris, S.E.* ; van der Most, P.J.* ; Nolte, I.M.* ; Munroe, P.B.* ; Palmer, N.D.* ; Kühnel, B. ; Weiss, S.* ; Wen, W.* ; Hall, K.A.* ; Lyytikäinen, L.P.* ; O'Connell, J.* ; Eiriksdottir, G.* ; Launer, L.J.* ; de Vries, P.S.* ; Arking, D.E.* ; Chen, H.* ; Boerwinkle, E.* ; Krieger, J.E.* ; Schreiner, P.J.* ; Sidney, S.* ; Shikany, J.M.* ; Rice, K.* ; Chen, Y.I.* ; Gharib, S.A.* ; Bis, J.C.* ; Luik, A.I.* ; Ikram, M.A.* ; Uitterlinden, A.G.* ; Amin, N.* ; Xu, H.* ; Levy, D.* ; He, J.* ; Lohman, K.K.* ; Zonderman, A.B.* ; Rice, T.K.* ; Sims, M.* ; Wilson, G.* ; Sofer, T.* ; Rich, S.S.* ; Palmas, W.* ; Yao, J.* ; Guo, X.* ; Rotter, J.I.* ; Biermasz, N.R.* ; Mook-Kanamori, D.O.* ; Martin, L.W.* ; Barac, A.* ; Wallace, R.B.* ; Gottlieb, D.J.* ; Komulainen, P.* ; Heikkinen, S.* ; Mägi, R.* ; Milani, L.* ; Metspalu, A.* ; Starr, J.M.* ; Milaneschi, Y.* ; Waken, R.J.* ; Gao, C.* ; Waldenberger, M. ; Peters, A. ; Strauch, K. ; Meitinger, T. ; Roenneberg, T.* ; Völker, U.* ; Dörr, M.* ; Shu, X.O.* ; Mukherjee, S.* ; Hillman, D.R.* ; Kähönen, M.* ; Wagenknecht, L.E.* ; Gieger, C. ; Grabe, H.J.* ; Zheng, W.* ; Palmer, L.J.* ; Lehtimäki, T.* ; Gudnason, V.* ; Morrison, A.C.* ; Pereira, A.C.* ; Fornage, M.* ; Psaty, B.M.* ; van Duijn, C.M.* ; Liu, C.T.* ; Kelly, T.N.* ; Evans, M.K.* ; Bouchard, C.* ; Fox, E.R.* ; Kooperberg, C.* ; Zhu, X.* ; Lakka, T.A.* ; Esko, T.* ; North, K.E.* ; Deary, I.J.* ; Snieder, H.* ; Penninx, B.W.J.H.* ; Gauderman, W.J.* ; Rao, D.C.* ; Redline, S.* ; van Heemst, D.*

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Mol. Psychiatry 26, 6293-6304 (2021)
Postprint DOI PMC
Open Access Green
Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint < 5 × 10-8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint < 5 × 10-8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint = 2 × 10-6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint < 10-3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Zeitschrift Molecular Psychiatry
Quellenangaben Band: 26, Heft: 11, Seiten: 6293-6304 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-001
G-504000-010
G-504100-001
G-500700-001
G-504091-004
Förderungen U.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD)
EC | European Commission - Executive Agency for SMEs | Competitiveness of Enterprises and Small and Medium-sized Enterprises (COSME)
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
DOI 10.1038/s41380-021-01087-0
WOS ID WOS:000640487900002
Scopus ID 85104697425
PubMed ID 33859359
Erfassungsdatum 2021-06-09
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