Journal article
Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits
HGG advances, Vol.2(1), 100013
01/14/2021
DOI: 10.1016/j.xhgg.2020.100013
PMCID: PMC8562625
PMID: 34734193
Abstract
Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
This genome-wide association study systematically evaluated the joint effect of SNPs and SNP-by-psychosocial factor interactions on BP in a large and diverse sample. Findings of the study underscore the importance of considering psychological and social factors in gene discovery for BP, especially in African ancestry.
Details
- Title: Subtitle
- Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits
- Creators
- Daokun Sun - The University of Texas Health Science Center at HoustonMelissa A. Richard - The University of Texas Health Science Center at HoustonSolomon K. Musani - University of Mississippi Medical CenterYun Ju Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USAThomas W. Winkler - University of RegensburgKaren Schwander - Washington University in St. LouisJin Fang Chai - National University of SingaporeXiuqing Guo - The Lundquist InstituteTuomas O. Kilpeläinen - Icahn School of Medicine at Mount SinaiDina Vojinovic - Erasmus MCHugues Aschard - Harvard UniversityTraci M. Bartz - University of WashingtonLawrence F. Bielak - University of MichiganMichael R. Brown - The University of Texas Health Science Center at HoustonKumaraswamy Chitrala - National Institutes of HealthFernando P. Hartwig - University of BristolAndrea R.V.R. Horimoto - Universidade de São PauloYongmei Liu - Duke UniversityAlisa K. Manning - Harvard UniversityRaymond Noordam - Leiden University Medical CenterAlbert V. Smith - University of MichiganSarah E. Harris - University of EdinburghBrigitte Kühnel - Helmholtz Zentrum MünchenLeo-Pekka Lyytikäinen - University of TampereIlja M. Nolte - University Medical Center GroningenRainer Rauramaa - Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio 70100, FinlandPeter J. van der Most - University Medical Center GroningenRujia Wang - University Medical Center GroningenErin B. Ware - University of MichiganStefan Weiss - Universitätsmedizin GreifswaldWanqing Wen - Vanderbilt UniversityLisa R. Yanek - Johns Hopkins MedicineDan E. Arking - Johns Hopkins MedicineDonna K. Arnett - University of KentuckyAna Barac - MedStar Heart and Vascular Institute, Washington, DC 20010, USAEric Boerwinkle - Baylor College of MedicineUlrich Broeckel - Medical College of WisconsinAravinda Chakravarti - New York UniversityYii-Der Ida Chen - The Lundquist InstituteL. Adrienne Cupples - Boston UniversityMartha L. Davigulus - University of Illinois ChicagoLisa de las Fuentes - Washington University in St. LouisRenée de Mutsert - Leiden University Medical CenterPaul S. de Vries - The University of Texas Health Science Center at HoustonJoseph A.C. Delaney - University of ManitobaAna V. Diez Roux - Drexel UniversityMarcus Dörr - Universitätsmedizin GreifswaldJessica D. Faul - University of MichiganAmanda M. Fretts - University of WashingtonLinda C. Gallo - San Diego State UniversityHans Jörgen Grabe - Universitätsmedizin GreifswaldC. Charles Gu - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USATamara B. Harris - National Institutes of HealthCatharina C.A. Hartman - University Medical Center GroningenSami Heikkinen - University of Eastern FinlandM. Arfan Ikram - Erasmus MCCarmen Isasi - Albert Einstein College of MedicineW. Craig Johnson - University of WashingtonJost Bruno Jonas - Capital Medical UniversityRobert C. Kaplan - Albert Einstein College of MedicinePirjo Komulainen - Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio 70100, FinlandJose E. Krieger - Universidade de São PauloDaniel Levy - Boston UniversityJianjun Liu - Agency for Science, Technology and ResearchKurt Lohman - Duke UniversityAnnemarie I. Luik - Erasmus MCLisa W. Martin - George Washington UniversityThomas Meitinger - Technical University of MunichYuri Milaneschi - Amsterdam UMC Location Vrije Universiteit AmsterdamJeff R. O’Connell - Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USAWalter R. Palmas - Columbia University Irving Medical CenterAnnette Peters - Helmholtz Zentrum MünchenPatricia A. Peyser - University of MichiganLaura Pulkki-Råback - University of HelsinkiLeslie J. Raffel - University of California, IrvineAlex P. Reiner - Fred Hutch Cancer CenterKenneth Rice - University of WashingtonJennifer G. Robinson - University of IowaFrits R. Rosendaal - Leiden University Medical CenterCarsten Oliver Schmidt - Universitätsmedizin GreifswaldPamela J. Schreiner - University of MinnesotaLars Schwettmann - Helmholtz Zentrum MünchenJames M. Shikany - University of Alabama at BirminghamXiao-ou Shu - Vanderbilt UniversityStephen Sidney - Kaiser PermanenteMario Sims - University of Mississippi Medical CenterJennifer A. Smith - University of MichiganNona Sotoodehnia - University of WashingtonKonstantin Strauch - Ludwig-Maximilians-Universität MünchenE. Shyong Tai - National University of SingaporeKent D. Taylor - The Lundquist InstituteAndré G. Uitterlinden - Erasmus MCCornelia M. van Duijn - University of OxfordMelanie Waldenberger - Helmholtz Zentrum MünchenHwee-Lin Wee - National University of SingaporeWen-Bin Wei - Capital Medical UniversityGregory Wilson - Jackson State UniversityDeng Xuan - Boston UniversityJie Yao - The Lundquist InstituteDonglin Zeng - University of North Carolina at Chapel HillWei Zhao - University of MichiganXiaofeng Zhu - Case Western Reserve UniversityAlan B. Zonderman - National Institutes of HealthDiane M. Becker - Johns Hopkins MedicineIan J. Deary - University of EdinburghChristian Gieger - Helmholtz Zentrum MünchenTimo A. Lakka - University of Eastern FinlandTerho Lehtimäki - University of TampereKari E. North - University of North Carolina at Chapel HillAlbertine J. Oldehinkel - University Medical Center GroningenBrenda W.J.H. Penninx - Amsterdam UMC Location Vrije Universiteit AmsterdamHarold Snieder - University Medical Center GroningenYa-Xing Wang - Capital Medical UniversityDavid R. Weir - University of MichiganWei Zheng - Vanderbilt UniversityMichele K. Evans - National Institutes of HealthW. James Gauderman - University of Southern CaliforniaVilmundur Gudnason - University of IcelandBernardo L. Horta - Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas RS 96010-610, BrazilChing-Ti Liu - Boston UniversityDennis O. Mook-Kanamori - Leiden University Medical CenterAlanna C. Morrison - The University of Texas Health Science Center at HoustonAlexandre C. Pereira - Universidade de São PauloBruce M. Psaty - University of WashingtonNajaf Amin - Erasmus MCErvin R. Fox - University of Mississippi Medical CenterCharles Kooperberg - Fred Hutch Cancer CenterXueling Sim - National University of SingaporeLaura Bierut - Washington University in St. LouisJerome I. Rotter - The Lundquist InstituteSharon L.R. Kardia - University of MichiganNora Franceschini - University of North Carolina at Chapel HillDabeeru C. Rao - Washington University in St. LouisMyriam Fornage - The University of Texas Health Science Center at HoustonLifelines Cohort Study
- Resource Type
- Journal article
- Publication Details
- HGG advances, Vol.2(1), 100013
- DOI
- 10.1016/j.xhgg.2020.100013
- PMID
- 34734193
- PMCID
- PMC8562625
- NLM abbreviation
- HGG Adv
- ISSN
- 2666-2477
- eISSN
- 2666-2477
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100007812, name: University of Washington; DOI: 10.13039/100007268, name: Washington University in St. Louis
- Language
- English
- Date published
- 01/14/2021
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984364400102771
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