Journal article
Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure
Molecular psychiatry, Vol.26(11), pp.6293-6304
11/2021
DOI: 10.1038/s41380-021-01087-0
PMCID: PMC8517040
PMID: 33859359
Abstract
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 P
< 5 × 10
), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P
< 5 × 10
). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P
= 2 × 10
). 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 (P
< 10
). 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.
Details
- Title: Subtitle
- Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure
- Creators
- Heming Wang - Broad InstituteRaymond Noordam - Leiden UniversityBrian E Cade - Broad InstituteKaren Schwander - Washington University in St. LouisThomas W Winkler - University of RegensburgJiwon Lee - University of PittsburghYun Ju Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USAAmy R Bentley - National Institutes of HealthAlisa K Manning - Broad InstituteHugues Aschard - Harvard UniversityTuomas O Kilpeläinen - Icahn School of Medicine at Mount SinaiMarjan Ilkov - Icelandic Heart AssociationMichael R Brown - The University of Texas Health Science Center at HoustonAndrea R Horimoto - Universidade de São PauloMelissa Richard - The University of Texas Health Science Center at HoustonTraci M Bartz - University of WashingtonDina Vojinovic - Leiden UniversityElise Lim - Boston UniversityJovia L Nierenberg - Tulane UniversityKumaraswamynaidu Chitrala - National Institutes of HealthYongmei Liu - Duke UniversityTuomo Rankinen - Pennington Biomedical Research CenterSolomon K Musani - University of MississippiNora Franceschini - University of North Carolina at Chapel HillRainer Rauramaa - University of Eastern FinlandMaris Alver - University of TartuPhyllis C Zee - Northwestern UniversitySarah E Harris - University of EdinburghPeter J van der Most - University of GroningenIlja M Nolte - University of GroningenPatricia B Munroe - Queen Mary University of LondonNicholette D Palmer - Wake Forest UniversityBrigitte Kühnel - Helmholtz Zentrum MünchenStefan Weiss - Universität GreifswaldWanqing Wen - Vanderbilt UniversityKelly A Hall - The University of AdelaideLeo-Pekka Lyytikäinen - University of TampereJeff O'Connell - University of Maryland, BaltimoreGudny Eiriksdottir - Icelandic Heart AssociationLenore J Launer - National Institutes of HealthPaul S de Vries - The University of Texas Health Science Center at HoustonDan E Arking - Johns Hopkins UniversityHan Chen - The University of Texas Health Science Center at HoustonEric Boerwinkle - Baylor College of MedicineJose E Krieger - Universidade de São PauloPamela J Schreiner - University of MinnesotaStephen Sidney - Kaiser PermanenteJames M Shikany - University of Alabama at BirminghamKenneth Rice - University of WashingtonYii-Der Ida Chen - University of California, Los AngelesSina A Gharib - University of WashingtonJoshua C Bis - University of WashingtonAnnemarie I Luik - Erasmus University RotterdamM Arfan Ikram - Erasmus University RotterdamAndré G Uitterlinden - Erasmus University RotterdamNajaf Amin - Erasmus University RotterdamHanfei Xu - Boston UniversityDaniel Levy - Boston UniversityJiang He - Tulane UniversityKurt K Lohman - Duke UniversityAlan B Zonderman - National Institutes of HealthTreva K Rice - Washington University in St. LouisMario Sims - University of MississippiGregory Wilson - Jackson State UniversityTamar Sofer - Broad InstituteStephen S Rich - University of VirginiaWalter Palmas - Columbia UniversityJie Yao - University of California, Los AngelesXiuqing Guo - University of California, Los AngelesJerome I Rotter - University of California, Los AngelesNienke R Biermasz - Leiden UniversityDennis O Mook-Kanamori - Leiden UniversityLisa W Martin - George Washington UniversityAna Barac - MedStar Heart and Vascular Institute, Washington, DC, USARobert B Wallace - University of IowaDaniel J Gottlieb - Harvard UniversityPirjo Komulainen - University of Eastern FinlandSami Heikkinen - University of Eastern FinlandReedik Mägi - University of TartuLili Milani - University of TartuAndres Metspalu - University of TartuJohn M Starr - University of EdinburghYuri Milaneschi - Vrije Universiteit AmsterdamR J Waken - Washington University in St. LouisChuan Gao - Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USAMelanie Waldenberger - Helmholtz Zentrum MünchenAnnette Peters - German Centre for Cardiovascular ResearchKonstantin Strauch - Ludwig-Maximilians-Universität MünchenThomas Meitinger - Helmholtz Zentrum MünchenTill Roenneberg - Ludwig-Maximilians-Universität MünchenUwe Völker - Universität GreifswaldMarcus Dörr - Universität GreifswaldXiao-Ou Shu - Vanderbilt UniversitySutapa Mukherjee - Flinders UniversityDavid R Hillman - Sir Charles Gairdner HospitalMika Kähönen - University of TampereLynne E Wagenknecht - Wake Forest UniversityChristian Gieger - German Center for Diabetes ResearchHans J Grabe - Universität GreifswaldWei Zheng - Vanderbilt UniversityLyle J Palmer - The University of AdelaideTerho Lehtimäki - University of TampereVilmundur Gudnason - University of IcelandAlanna C Morrison - The University of Texas Health Science Center at HoustonAlexandre C Pereira - Universidade de São PauloMyriam Fornage - The University of Texas Health Science Center at HoustonBruce M Psaty - University of WashingtonCornelia M van Duijn - University of OxfordChing-Ti Liu - Boston UniversityTanika N Kelly - Tulane UniversityMichele K Evans - National Institutes of HealthClaude Bouchard - Pennington Biomedical Research CenterErvin R Fox - University of MississippiCharles Kooperberg - Fred Hutch Cancer CenterXiaofeng Zhu - Case Western Reserve UniversityTimo A Lakka - University of Eastern FinlandTõnu Esko - University of TartuKari E North - University of North Carolina at Chapel HillIan J Deary - University of EdinburghHarold Snieder - University of GroningenBrenda W J H Penninx - Vrije Universiteit AmsterdamW James Gauderman - University of Southern CaliforniaDabeeru C Rao - Washington University in St. LouisSusan Redline - Harvard UniversityDiana van Heemst - Leiden University
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.26(11), pp.6293-6304
- DOI
- 10.1038/s41380-021-01087-0
- PMID
- 33859359
- PMCID
- PMC8517040
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Grant note
- K01 HL135405 / NHLBI NIH HHS ZIA HG200362 / Intramural NIH HHS R01-MD012765 / U.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD) R03 HL154284 / NHLBI NIH HHS R01 HL105756 / NHLBI NIH HHS R01 HL118305 / NHLBI NIH HHS R01 HL046380 / NHLBI NIH HHS P30 DK079626 / NIDDK NIH HHS R35 HL135818 / NHLBI NIH HHS R01 AG058921 / NIA NIH HHS R21-HL140385 / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 HL153814 / NHLBI NIH HHS R01 HL113338 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363607202771
Metrics
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