Journal article
Large-scale blood pressure GWAS accounting for gene-depression interactions in 564,680 individuals from diverse populations
HGG advances, v 7(2), 100566
09 Apr 2026
PMID: 41520179
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 were derived from non-European populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions (DOCK4 and MAGI2) and neuronal signaling (CCK, UGDH, and SLC01A2). Integrative druggability analyses identified 11 druggable candidate gene targets linked to pathways involved in mood disorders as well as known anti-hypertensive drugs. Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.
We conducted a genome-wide interaction study of blood pressure (BP) traits in 564,680 adults that identified 16 BP loci exhibiting gene-depressive symptomatology interactions. Prioritized genes at these loci pointed to druggable targets linked to pathways involved in mood disorders as well as known anti-hypertensive drugs.
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- Title
- Large-scale blood pressure GWAS accounting for gene-depression interactions in 564,680 individuals from diverse populations
- Creators
- Lifelines Cohort Study (Collaboration)Songmi Lee - Seoul National UniversityClint L. Miller - University of Virginia Health SystemAmy R. Bentley - National Institutes of HealthMichael R. Brown - The University of Texas Health Science Center at HoustonPavithra Nagarajan - Brigham and Women's HospitalRaymond Noordam - Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the NetherlandsJohn L Morrison - University of Southern CaliforniaKaren Schwander - Washington University in St. Louis School of MedicineKenneth Westerman - Massachusetts General HospitalMinjung Kho - Seoul National UniversityAldi T. Kraja - Jackson Memorial HospitalPaul S. de Vries - The University of Texas Health Science Center at HoustonFarah Ammous - Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USAHughes Aschard - Institut PasteurTraci M. Bartz - University of WashingtonAnh Do - Washington University in St. LouisCharles T. Dupont - Vanderbilt University Medical CenterMary F. Feitosa - Washington University in St. Louis School of MedicineValborg Gudmundsdottir - Icelandic Heart AssociationXiuqing Guo - The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USASarah E. Harris - Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UKKeiko Hikino - RIKEN Center for Integrative Medical SciencesZhijie Huang - Tulane UniversityChristophe Lefevre - Hunter Medical Research InstituteLeo-Pekka Lyytikäinen - Finnish Cardiovascular Research Center – Tampere, Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandYuri Milaneschi - Department of Psychiatry, Amsterdam UMC/Vrije Universiteit, Amsterdam, the NetherlandsGiuseppe Giovanni Nardone - University of TriesteAurora Santin - IRCCS Materno Infantile Burlo GarofoloHelena Schmidt - Medical University of GrazBotong Shen - National Institute on AgingTamar Sofer - Beth Israel Deaconess Medical CenterQuan Sun - University of North Carolina at Chapel HillYe An Tan - National University of SingaporeJingxian Tang - Boston UniversitySébastien Thériault - Institut universitaire de cardiologie et de pneumologie de QuébecPeter J. van der Most - University Medical Center GroningenErin B. Ware - University of MichiganStefan Weiss - Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, GermanyWang Ya Xing - Capital Medical UniversityChenglong Yu - Monash UniversityWei Zhao - University of MichiganMd Abu Yusuf Ansari - University of Mississippi Medical CenterPramod Anugu - Jackson Memorial HospitalJohn R. Attia - University of Newcastle AustraliaLydia A. Bazzano - Tulane UniversityJoshua C. Bis - Columbia UniversityMax Breyer - Vanderbilt University Medical CenterBrian Cade - Brigham and Women's HospitalGuanjie Chen - National Institutes of HealthStacey Collins - University of MichiganJanie Corley - NHS LothianGail Davies - NHS LothianMarcus Dörr - German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, GermanyJiawen Du - University of North Carolina at Chapel HillTodd L. Edwards - Vanderbilt University Medical CenterTariq Faquih - Brigham and Women's HospitalJessica D. Faul - University of MichiganAlison E. Fohner - University of WashingtonAmanda M. Fretts - Group Health CooperativeSrushti Gangireddy - Vanderbilt University Medical CenterAdam Gepner - University of Wisconsin–MadisonMariaElisa Graff - University of North Carolina at Chapel HillEdith Hofer - Medical University of GrazGeorg Homuth - Universitätsmedizin GreifswaldMichelle M. Hood - University of MichiganXu Jie - Beijing Tongren HospitalMika Kähönen - Tampere University HospitalSharon L.R. Kardia - University of MichiganCarrie A. Karvonen-Gutierrez - University of MichiganLenore J. Launer - National Institutes of HealthDaniel Levy - Framingham Heart StudyMaitreiyi Maheshwari - Broad InstituteLisa W. Martin - George Washington UniversityKoichi Matsuda - The University of TokyoJohn J. McNeil - Monash UniversityIlja M. Nolte - Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsTomo Okochi - Fujita Health UniversityLaura M. Raffield - University of North Carolina at Chapel HillOlli T. Raitakari - Turku University HospitalLorenz Risch - University of LiechtensteinMartin Risch - Kantonsspital GraubündenAna V Diez Roux - Drexel University, Epidemiology and BiostatisticsEdward A. Ruiz-Narvaez - University of MichiganTom C. Russ - University of EdinburghTakeo Saito - Fujita Health UniversityPamela J. Schreiner - University of MinnesotaRodney J. Scott - University of Newcastle AustraliaJames Shikany - University of AlabamaJennifer A. Smith - University of MichiganHarold Snieder - University of GroningenBeatrice Spedicati - IRCCS Materno Infantile Burlo GarofoloE. Shyong Tai - National University Health SystemAdele M. Taylor - NHS LothianKent D. Taylor - UCLA Medical CenterPaola Tesolin - IRCCS Materno Infantile Burlo GarofoloRob M. van Dam - National University Health SystemRujia Wang - Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsWei Wenbin - Beijing Tongren HospitalTian Xie - University Medical Center GroningenJie Yao - The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USAKristin L. Young - University of North Carolina at Chapel HillRuiyuan Zhang - Tulane UniversityAlan B. Zonderman - National Institutes of HealthMaria Pina Concas - IRCCS Materno Infantile Burlo GarofoloDavid Conen - Population Health Research InstituteSimon R. Cox - NHS LothianMichele K. Evans - Laboratory of Epidemiology and Population Sciences, Health Disparities Research Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, USAErvin R. Fox - Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USALisa de las Fuentes - Center for Biostatistics and Data Science, Institute for Informatics, Data Science, and Biostatistics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USAAyush Giri - Vanderbilt University Medical CenterGiorgia Girotto - IRCCS Materno Infantile Burlo GarofoloHans J. Grabe - Universitätsmedizin GreifswaldCharles Gu - Washington University in St. LouisVilmundur Gudnason - University of IcelandSioban D. Harlow - University of MichiganElizabeth Holliday - University of Newcastle AustraliaJonas B. Jost - Institut FrançaisPaul Lacaze - Monash UniversitySeunggeun Lee - Graduate School of Data Science, Seoul National University, Seoul, South KoreaTerho Lehtimäki - Finnish Cardiovascular Research Center – Tampere, Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandChangwei Li - Tulane UniversityChing-Ti Liu - Boston UniversityAlanna C. Morrison - The University of Texas Health Science Center at HoustonKari E. North - University of North Carolina at Chapel HillBrenda W.J.H. Penninx - Department of Psychiatry, Amsterdam UMC/Vrije Universiteit, Amsterdam, the NetherlandsPatricia A. Peyser - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USAMichael M. Province - Washington University in St. Louis School of MedicineBruce M. Psaty - Kaiser Permanente Washington Health Research InstituteSusan Redline - Brigham and Women's HospitalFrits R. Rosendaal - Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the NetherlandsCharles N. Rotimi - National Human Genome Research InstituteJerome I. Rotter - The Lundquist InstituteReinhold Schmidt - Medical University of GrazXueling Sim - National University of SingaporeChikashi Terao - University of ShizuokaDavid R. Weir - University of MichiganXiaofeng Zhu - Case Western Reserve UniversityNora Franceschini - University of North Carolina at Chapel HillJeffrey R. O’Connell - Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USACashell E. Jaquish - National Heart Lung and Blood InstituteHeming Wang - Brigham and Women's HospitalAlisa Manning - Metabolism Program, Broad Institute of MIT and Harvard, Cambridge, MA, USAPatricia B. Munroe - Queen Mary University of LondonDabeeru C. Rao - Center for Biostatistics and Data Science, Institute for Informatics, Data Science, and Biostatistics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USAHan Chen - The University of Texas Health Science Center at HoustonW. James Gauderman - Division of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USALaura J Bierut - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USAThomas W. Winkler - University of RegensburgMyriam Fornage - The University of Texas Health Science Center at Houston
- Publication Details
- HGG advances, v 7(2), 100566
- Publisher
- Elsevier Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative; Epidemiology and Biostatistics
- Web of Science ID
- WOS:001693001000001
- Scopus ID
- 2-s2.0-105028859481
- Other Identifier
- 991022180002104721
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- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity