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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


AUTHORS

Nagarajan 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 , van Dijk KW , 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 , . medRxiv : the preprint server for health sciences. 2024 3 8; ().

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 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.



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