Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study
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 controll...
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| Language: | English |
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Wiley
2024-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.034180 |
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| author | Kosuke Inoue Tatsuhiko Naito Ryosuke Fuji Kyuto Sonehara Kenichi Yamamoto Ryuta Baba Takaya Kodama Yu Otagaki Akira Okada Kiyotaka Itcho Kazuhiro Kobuke Haruya Ohno Takayuki Morisaki Noboru Hattori Atsushi Goto Tetsuo Nishikawa Kenji Oki Yukinori Okada |
| author_facet | Kosuke Inoue Tatsuhiko Naito Ryosuke Fuji Kyuto Sonehara Kenichi Yamamoto Ryuta Baba Takaya Kodama Yu Otagaki Akira Okada Kiyotaka Itcho Kazuhiro Kobuke Haruya Ohno Takayuki Morisaki Noboru Hattori Atsushi Goto Tetsuo Nishikawa Kenji Oki Yukinori Okada |
| author_sort | Kosuke Inoue |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d8c02857d41640e2a219bc6762859cf6 |
| institution | OA Journals |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-d8c02857d41640e2a219bc6762859cf62025-08-20T02:27:32ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-08-01131510.1161/JAHA.123.034180Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization StudyKosuke Inoue0Tatsuhiko Naito1Ryosuke Fuji2Kyuto Sonehara3Kenichi Yamamoto4Ryuta Baba5Takaya Kodama6Yu Otagaki7Akira Okada8Kiyotaka Itcho9Kazuhiro Kobuke10Haruya Ohno11Takayuki Morisaki12Noboru Hattori13Atsushi Goto14Tetsuo Nishikawa15Kenji Oki16Yukinori Okada17Department of Social Epidemiology, Graduate School of Medicine Kyoto University Kyoto JapanDepartment of Statistical Genetics Osaka University Graduate School of Medicine Suita JapanInstitute for Biomedicine (Affiliated to the University of Lübeck) Eurac Research Bolzano ItalyDepartment of Statistical Genetics Osaka University Graduate School of Medicine Suita JapanDepartment of Statistical Genetics Osaka University Graduate School of Medicine Suita JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDivision of Molecular Pathology, Institute of Medical Science The University of Tokyo Tokyo JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Public Health Yokohama City University Yokohama JapanEndocrinology and Diabetes Center Yokohama Rosai Hospital Yokohama JapanDepartment of Molecular and Internal Medicine Hiroshima University Hiroshima JapanDepartment of Statistical Genetics Osaka University Graduate School of Medicine Suita JapanBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.123.034180cardiovascular diseasecross‐ancestry meta‐analysisgenome‐wide association studiesMendelian randomizationprimary aldosteronism |
| spellingShingle | Kosuke Inoue Tatsuhiko Naito Ryosuke Fuji Kyuto Sonehara Kenichi Yamamoto Ryuta Baba Takaya Kodama Yu Otagaki Akira Okada Kiyotaka Itcho Kazuhiro Kobuke Haruya Ohno Takayuki Morisaki Noboru Hattori Atsushi Goto Tetsuo Nishikawa Kenji Oki Yukinori Okada Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular disease cross‐ancestry meta‐analysis genome‐wide association studies Mendelian randomization primary aldosteronism |
| title | Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study |
| title_full | Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study |
| title_fullStr | Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study |
| title_full_unstemmed | Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study |
| title_short | Primary Aldosteronism and Risk of Cardiovascular Outcomes: Genome‐Wide Association and Mendelian Randomization Study |
| title_sort | primary aldosteronism and risk of cardiovascular outcomes genome wide association and mendelian randomization study |
| topic | cardiovascular disease cross‐ancestry meta‐analysis genome‐wide association studies Mendelian randomization primary aldosteronism |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.034180 |
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