Discovery of gene-alcohol interaction loci influencing blood pressure in 1.1 million individuals from multiple populations

Authors

• Mary Feitosa, Washington School of Medicine.
• Karen Schwander, Washington University.
• Clint Miller, University of Virginia.
• Aldi Kraja, University of Mississippi Medical Center.
• Amy Bentley, National Institutes of Health, NHGRI.
• Michael Brown, The University of Texas Health Science Center at Houston.
• Hannah de Hesselle, University of Regensburg.
• Raymond Noordam, Leiden University Medical Center.
• Songmi Lee, University of Texas Health Science Center at Houston, McGovern Medical School.
• Pavithra Nagarajan, Brigham and Women's Hospital.
• Heming Wang, Brigham and Women's Hospital; Harvard Medical School.
• Ayush Giri, Vanderbilt University Medical Center.
• Farrah Ammous, University of Michigan.
• Traci Bartz, University of Washington.
• Chiara Batini, University of Leicester.
• Jean-Tristan Brandenburg
• Max Breyer, Vanderbilt University School of Medicine.
• Heather Cordell, Newcastle University.
• Janie Corley, University of Edinburgh.
• Latchezar Dimotrov, Wake Forest University School of Medicine.
• Anh Do, Washington University School of Medicine, St. Louis, MO, USA.
• Jiawen Du
• Franco Giulianini, Brigham and Women's Hospital.
• Christopher Grace, Radcliffe Department of Medicine, University of Oxford.
• Valborg Gudmundsdottir, Faculty of Medicine, University of Iceland.
• Xiuqing Guo
• Sarah Harris, Lothian Birth Cohorts, Dept. Psychology.
• Natalie Hasbani, The University of Texas Health Science Center at Houston.
• Janina Herold, University of Regensburg.
• Keiko Hikino, RIKEN.
• Edith Hofer, Medical University Graz.
• Andrea Horimoto, Brigham and Women's Hospital.

Document Type

Journal Article

Publication Date

4-3-2026

Journal

Research square

DOI

10.21203/rs.3.rs-9283196/v1

Abstract

Genetic predisposition and alcohol consumption are risk factors for increased blood pressure (BP), but their interactions influencing BP remain understudied. We conducted population-specific and cross-population meta-analyses of genome-wide gene-alcohol (GxAlc) interactions affecting BP in >1.1M individuals from multiple populations. We identified 46 GxAlc interaction loci for BP, including 21 from one-degree-of-freedom interaction tests (PGxAlc<5×10-8; or <0.05/Meff, Meff independent BP associations at P<10-5), and 25 from two-degree-of-freedom tests of main and interaction effects (PGxAlc<0.05/M2df, M2df independent 2df-associations at P2df<5×10-8), including 7 novel and 39 known BP loci. The 12q24 locus highlights the genetic effect of BRAP-rs11066001 on BP, being ~6 times larger in current drinkers than in non-drinkers. Gene prioritization with 46 GxAlc loci identified 15 genes with ≥3 lines of evidence (location, literature, druggability, functional/regulatory annotation, or pathway analyses). Several loci showed sex- and population-specific effects and revealed biological pathways of alcohol's influence on BP, suggesting mechanisms underlying alcohol-induced hypertension.

APA Citation

Feitosa, Mary; Schwander, Karen; Miller, Clint; Kraja, Aldi; Bentley, Amy; Brown, Michael; de Hesselle, Hannah; Noordam, Raymond; Lee, Songmi; Nagarajan, Pavithra; Wang, Heming; Giri, Ayush; Ammous, Farrah; Bartz, Traci; Batini, Chiara; Brandenburg, Jean-Tristan; Breyer, Max; Cordell, Heather; Corley, Janie; Dimotrov, Latchezar; Do, Anh; Du, Jiawen; Giulianini, Franco; Grace, Christopher; Gudmundsdottir, Valborg; Guo, Xiuqing; Harris, Sarah; Hasbani, Natalie; Herold, Janina; Hikino, Keiko; Hofer, Edith; and Horimoto, Andrea, "Discovery of gene-alcohol interaction loci influencing blood pressure in 1.1 million individuals from multiple populations" (2026). GW Authored Works. Paper 9119.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/9119

Department

Exercise and Nutrition Sciences