Academic Journal
Genome-wide association study of heart failure in a multiethnic south-east asian cohort
| العنوان: | Genome-wide association study of heart failure in a multiethnic south-east asian cohort |
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| المؤلفون: | Loong, S, Hong, P, Goh, V J L, Lee, S S G, Loh, S Y, Soon, D, Chin, C W L, Maurer-Stroh, S, Amikeng, F, Loh, M, Wang, D, Lam, C S P, Richards, M, Foo, R |
| المصدر: | European Heart Journal ; volume 44, issue Supplement_2 ; ISSN 0195-668X 1522-9645 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| الوصف: | NMRC Heart failure (HF) is a leading cause of morbidity and mortality worldwide (1). While existing genome-wide association studies (GWAS) have yielded many different loci and causal genes, most of such studies has been conducted in European populations (2). There has been little insight into the genetic architecture of complex diseases, especially HF among Asians, despite up to 60% of the world population consisting of Asians. Through this study, we aim to uncover the genomic basis of heart failure in a South-East Asian cohort, with deep phenotyping of cardiovascular, metabolic, immune, and inflammatory traits. We conducted the largest multi-ancestry South-east Asian all-cause HF GWAS (n=2310, 1305 cases and 1005 controls), utilizing whole genome sequencing (WGS) data. Eleven independent loci were found to be associated with HF (P-value = 5e10-8). In-silico and functional studies were interrogated, allowing us to map most of the loci (n=9) to various genes implicated in various metabolic diseases - hypertension (HTN), diabetes mellitus (DM), and coronary artery disease (CAD). We further conducted a phenome-wide association study (PWAS) of significant loci, which revealed that they augment signals related to CAD, atrial fibrillation, DM and HTN, suggesting a shared genetic etiology between these metabolic risk factors and Asian HF. Of note, this the first HF GWAS to implicate the PDE9A gene, which was previously discovered as a potential biomarker for HF with preserved ejection fraction (HFpEF) through its involvement in the cGMP signaling pathways, and is currently being explored as a therapeutic target in the treatment of HFpEF (3). Polygenic risk scores (PRS) were calculated for heart failure in this Asian cohort, which identified that the most optimized model (HF PRS), included 19,431 of the most significant genetic variants (p=0.073). The prediction power of the HF PRS on HF risk was tested in UKB Asian subjects (N=10,016; 413 cases and 9,603 controls). Our results showed that the highest 10% ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/eurheartj/ehad655.721 |
| الاتاحة: | https://doi.org/10.1093/eurheartj/ehad655.721 https://academic.oup.com/eurheartj/article-pdf/44/Supplement_2/ehad655.721/53600246/ehad655.721.pdf |
| Rights: | https://academic.oup.com/pages/standard-publication-reuse-rights |
| رقم الانضمام: | edsbas.1F49567A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/eurheartj/ehad655.721 |
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