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Genome-wide analysis yields new loci associating with aortic valve stenosis

Genome-wide analysis yields new loci associating with aortic valve stenosis

Title: Genome-wide analysis yields new loci associating with aortic valve stenosis
Author: Helgadottir, Anna   orcid.org/0000-0002-1806-2467
Thorleifsson, Gudmar   orcid.org/0000-0003-4623-9087
Grétarsdóttir, Sólveig
Stefánsson, Ólafur A.
Tragante, Vinicius
Þórólfsdóttir, Rósa B.
Jonsdottir, Ingileif   orcid.org/0000-0001-8339-150X
Björnsson, Þorsteinn
Steinthorsdottir, Valgerdur   orcid.org/0000-0003-1846-6274
Verweij, Niek
... 36 more authors Show all authors
Date: 2018-03-07
Language: English
Scope: 987
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Nature Communications;9(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-018-03252-6
Subject: Congenital heart defects; Genome-wide association studies; Heart development; Valvular disease; Blóðrásarsjúkdómar; Arfgengi; Erfðafræði; Erfðarannsóknir
URI: https://hdl.handle.net/20.500.11815/737

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Helgadottir, A., Thorleifsson, G., Gretarsdottir, S., Stefansson, O. A., Tragante, V., Thorolfsdottir, R. B., . . . Stefansson, K. (2018). Genome-wide analysis yields new loci associating with aortic valve stenosis. Nature Communications, 9(1), 987. doi:10.1038/s41467-018-03252-6


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.


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