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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

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

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. More... »

PAGES

987

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-03252-6

    DOI

    http://dx.doi.org/10.1038/s41467-018-03252-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101298929

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29511194


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