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

被引：4

作者：

Inoue, Kosuke

Naito, Tatsuhiko ^{[2
]}

Fuji, Ryosuke ^{[3
,4
]}

Sonehara, Kyuto ^{[1
,2
,5
]}

Yamamoto, Kenichi ^{[1
]}

Baba, Ryuta ^{[6
]}

Kodama, Takaya ^{[6
]}

Otagaki, Yu ^{[6
]}

Okada, Akira ^{[6
]}

Itcho, Kiyotaka ^{[6
]}

Kobuke, Kazuhiro ^{[6
]}

Ohno, Haruya ^{[6
]}

Morisaki, Takayuki ^{[7
,8
]}

Hattori, Noboru ^{[6
]}

Goto, Atsushi ^{[9
]}

Nishikawa, Tetsuo ^{[1
,10
]}

Oki, Kenji ^{[6
]}

Okada, Yukinori ^{[1
,2
,5
,11
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Stat Genet, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[2] RIKEN Ctr Integrat Med Sci, Lab Syst Genet, Yokohama, Kanagawa, Japan

[3] Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy

[4] Fujita Hlth Univ, Sch Med Sci, Dept Prevent Med Sci, Toyoake, Aichi, Japan

[5] Univ Tokyo, Grad Sch Med, Dept Genome Informat, Tokyo, Japan

[6] Hiroshima Univ, Dept Mol & Internal Med, Hiroshima, Japan

[7] Univ Tokyo, Inst Med Sci, Div Mol Pathol, Tokyo, Japan

[8] Univ Tokyo Hosp, Inst Med Sci, Dept Internal Med, Tokyo, Japan

[9] Yokohama City Univ, Dept Publ Hlth, Yokohama, Kanagawa, Japan

[10] Yokohama Rosai Hosp, Endocrinol & Diabet Ctr, Yokohama, Kanagawa, Japan

[11] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Integrated Frontier Res Med Sci Div, Suita, Osaka, Japan

来源：

JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2024年 / 13卷 / 15期

基金：

日本学术振兴会;

关键词：

cardiovascular disease; cross-ancestry meta-analysis; genome-wide association studies; Mendelian randomization; primary aldosteronism; HYPERTENSION; INFLAMMATION; MUTATIONS; DIAGNOSIS; BIAS;

D O I：

10.1161/JAHA.123.034180

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：10

共 44 条

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