Dataset Information

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

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.

SUBMITTER: Nagarajan P

PROVIDER: S-EPMC10942520 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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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.

Nagarajan Pavithra P Winkler Thomas W TW Bentley Amy R AR Miller Clint L CL Kraja Aldi T AT Schwander Karen K Lee Songmi S Wang Wenyi W Brown Michael R MR Morrison John L JL Giri Ayush A O'Connell Jeffrey R JR Bartz Traci M TM de Las Fuentes Lisa L Gudmundsdottir Valborg V Guo Xiuqing X Harris Sarah E SE Huang Zhijie Z Kals Mart M Kho Minjung M Lefevre Christophe C Luan Jian'an J Lyytikäinen Leo-Pekka LP Mangino Massimo M Milaneschi Yuri Y Palmer Nicholette D ND Rao Varun V Rauramaa Rainer R Shen Botong B Stadler Stefan S Sun Quan Q Tang Jingxian J Thériault Sébastien S van der Graaf Adriaan A van der Most Peter J PJ Wang Yujie Y Weiss Stefan S Westerman Kenneth E KE Yang Qian Q Yasuharu Tabara T Zhao Wei W Zhu Wanying W Altschul Drew D Ansari Md Abu Yusuf MAY Anugu Pramod P Argoty-Pantoja Anna D AD Arzt Michael M Aschard Hugues H Attia John R JR Bazzanno Lydia L Breyer Max A MA Brody Jennifer A JA Cade Brian E BE Chen Hung-Hsin HH Ida Chen Yii-Der YD Chen Zekai Z de Vries Paul S PS Dimitrov Latchezar M LM Do Anh A Du Jiawen J Dupont Charles T CT Edwards Todd L TL Evans Michele K MK Faquih Tariq T Felix Stephan B SB Fisher-Hoch Susan P SP Floyd James S JS Graff Mariaelisa M Gu Charles C Gu Dongfeng D Hairston Kristen G KG Hanley Anthony J AJ Heid Iris M IM Heikkinen Sami S Highland Heather M HM Hood Michelle M MM Kähönen Mika M Karvonen-Gutierrez Carrie A CA Kawaguchi Takahisa T Kazuya Setoh S Kelly Tanika N TN Komulainen Pirjo P Levy Daniel D Lin Henry J HJ Liu Peter Y PY Marques-Vidal Pedro P McCormick Joseph B JB Mei Hao H Meigs James B JB Menni Cristina C Nam Kisung K Nolte Ilja M IM Pacheco Natasha L NL Petty Lauren E LE Polikowsky Hannah G HG Province Michael A MA Psaty Bruce M BM Raffield Laura M LM Raitakari Olli T OT Rich Stephen S SS Riha Renata L RL Risch Lorenz L Risch Martin M Ruiz-Narvaez Edward A EA Scott Rodney J RJ Sitlani Colleen M CM Smith Jennifer A JA Sofer Tamar T Teder-Laving Maris M Völker Uwe U Vollenweider Peter P Wang Guanchao G van Dijk Ko Willems KW Wilson Otis D OD Xia Rui R Yao Jie J Young Kristin L KL Zhang Ruiyuan R Zhu Xiaofeng X Below Jennifer E JE Böger Carsten A CA Conen David D Cox Simon R SR Dörr Marcus M Feitosa Mary F MF Fox Ervin R ER Franceschini Nora N Gharib Sina A SA Gudnason Vilmundur V Harlow Sioban D SD He Jiang J Holliday Elizabeth G EG Kutalik Zoltan Z Lakka Timo A TA Lawlor Deborah A DA Lee Seunggeun S Lehtimäki Terho T Li Changwei C Liu Ching-Ti CT Mägi Reedik R Matsuda Fumihiko F Morrison Alanna C AC Penninx Brenda Wjh BW Peyser Patricia A PA Rotter Jerome I JI Snieder Harold H Spector Tim D TD Wagenknecht Lynne E LE Wareham Nicholas J NJ Zonderman Alan B AB North Kari E KE Fornage Myriam M Hung Adriana M AM Manning Alisa K AK Gauderman James J Chen Han H Munroe Patricia B PB Rao Dabeeru C DC van Heemst Diana D Redline Susan S Noordam Raymond R Wang Heming H

medRxiv : the preprint server for health sciences 20240308

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 interact ...[more]

PMID: 38496537

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Project description:Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans.

Dataset Information

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

Publications

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

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