Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome-Wide Association and Mendelian Randomization Study.

Autor: Inoue K; Department of Social Epidemiology, Graduate School of Medicine Kyoto University Kyoto Japan.; Hakubi Center for Advanced Research Kyoto University Kyoto Japan., Naito T; Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan.; Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Kanagawa Japan., Fuji R; Institute for Biomedicine (Affiliated to the University of Lübeck) Eurac Research Bolzano Italy.; Department of Preventive Medical Science Fujita Health University School of Medical Sciences Toyoake Japan., Sonehara K; Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan.; Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Kanagawa Japan.; Department of Genome Informatics, Graduate School of Medicine The University of Tokyo Tokyo Japan., Yamamoto K; Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan., Baba R; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Kodama T; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Otagaki Y; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Okada A; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Itcho K; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Kobuke K; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Ohno H; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Morisaki T; Division of Molecular Pathology, Institute of Medical Science The University of Tokyo Tokyo Japan.; Department of Internal Medicine, Institute of Medical Science The University of Tokyo Hospital Tokyo Japan., Hattori N; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Goto A; Department of Public Health Yokohama City University Yokohama Japan., Nishikawa T; Endocrinology and Diabetes Center Yokohama Rosai Hospital Yokohama Japan., Oki K; Department of Molecular and Internal Medicine Hiroshima University Hiroshima Japan., Okada Y; Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan.; Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Kanagawa Japan.; Department of Genome Informatics, Graduate School of Medicine The University of Tokyo Tokyo Japan.; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives Osaka University Suita Japan.
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2024 Aug 06; Vol. 13 (15), pp. e034180. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1161/JAHA.123.034180
Abstrakt: Background: Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke.
Methods and Results: Cross-ancestry meta-analysis of genome-wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single-nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2-sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome-wide association studies consortia. Our cross-ancestry meta-analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1 , WNT2B , HOTTIP , LSP1 , TBX3 , RXFP2 , and NDP . Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03-1.11) for CAD, 1.10 (95% CI, 1.01-1.20) for CHF, and 1.13 (95% CI, 1.09-1.18) for stroke. The results were consistent among the European population.
Conclusions: Our 2-sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.
Databáze: MEDLINE
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