| Title: | Genome-wide analysis yields new loci associating with aortic valve stenosis |
| Journal: | Nature Communications |
| Published: | 7 Mar 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29511194/ |
| DOI: | https://doi.org/10.1038/s41467-018-03252-6 |
| URL: | https://www.nature.com/articles/s41467-018-03252-6.pdf |
Publication 8511
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Abstract
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10−22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10−13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10−10) and aortic root diameter (P = 1.30 × 10−8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10−3) and coronary artery disease (OR = 1.05, P = 9.3 × 10−5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.</p>
46 Authors
- Anna Helgadottir
- Gudmar Thorleifsson
- Solveig Gretarsdottir
- Olafur A. Stefansson
- Vinicius Tragante
- Rosa B. Thorolfsdottir
- Ingileif Jonsdottir
- Thorsteinn Bjornsson
- Valgerdur Steinthorsdottir
- Niek Verweij
- Jonas B. Nielsen
- Wei Zhou
- Lasse Folkersen
- Andreas Martinsson
- Mahyar Heydarpour
- Siddharth Prakash
- Gylfi Oskarsson
- Tomas Gudbjartsson
- Arnar Geirsson
- Isleifur Olafsson
- Emil L. Sigurdsson
- Peter Almgren
- Olle Melander
- Anders Franco-Cereceda
- Anders Hamsten
- Lars Fritsche
- Maoxuan Lin
- Bo Yang
- Whitney Hornsby
- Dongchuan Guo
- Chad M. Brummett
- Gonçalo Abecasis
- Michael Mathis
- Dianna Milewicz
- Simon C. Body
- Per Eriksson
- Cristen J. Willer
- Kristian Hveem
- Christopher Newton-Cheh
- J. Gustav Smith
- Ragnar Danielsen
- Gudmundur Thorgeirsson
- Unnur Thorsteinsdottir
- Daniel F. Gudbjartsson
- Hilma Holm
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 15293 | Genetic dissection of the relationships of myocardial diseases and their risk factors |
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