Gustav Smith
Associate professor
Genome-wide analysis yields new loci associating with aortic valve stenosis
Author
Summary, in English
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.
Department/s
- Cardiology
- Department of Clinical Sciences, Malmö
- Cardiovascular Research - Hypertension
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
Publishing year
2018-12-01
Language
English
Publication/Series
Nature Communications
Volume
9
Issue
1
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Cardiac and Cardiovascular Systems
- Medical Genetics
Status
Published
Research group
- Cardiovascular Research - Hypertension
ISBN/ISSN/Other
- ISSN: 2041-1723