dc.contributor |
Háskóli Íslands |
dc.contributor |
University of Iceland |
dc.contributor.author |
Helgadottir, Anna |
dc.contributor.author |
Thorleifsson, Gudmar |
dc.contributor.author |
Grétarsdóttir, Sólveig |
dc.contributor.author |
Stefánsson, Ólafur A. |
dc.contributor.author |
Tragante, Vinicius |
dc.contributor.author |
Þórólfsdóttir, Rósa B. |
dc.contributor.author |
Jonsdottir, Ingileif |
dc.contributor.author |
Björnsson, Þorsteinn |
dc.contributor.author |
Steinthorsdottir, Valgerdur |
dc.contributor.author |
Verweij, Niek |
dc.contributor.author |
Nielsen, Jonas B. |
dc.contributor.author |
Zhou, Wei |
dc.contributor.author |
Folkersen, Lasse |
dc.contributor.author |
Martinsson, Andreas |
dc.contributor.author |
Heydarpour, Mahyar |
dc.contributor.author |
Prakash, Siddharth |
dc.contributor.author |
Óskarsson, Gylfi |
dc.contributor.author |
Gudbjartsson, Tomas |
dc.contributor.author |
Geirsson, Arnar |
dc.contributor.author |
Olafsson, Isleifur |
dc.contributor.author |
Sigurðsson, Emil Lárus |
dc.contributor.author |
Almgren, Peter |
dc.contributor.author |
Melander, Olle |
dc.contributor.author |
Franco-Cereceda, Anders |
dc.contributor.author |
Hamsten, Anders |
dc.contributor.author |
Fritsche, Lars |
dc.contributor.author |
Lin, Maoxuan |
dc.contributor.author |
Yang, Bo |
dc.contributor.author |
Hornsby, Whitney |
dc.contributor.author |
Guo, Dongchuan |
dc.contributor.author |
Brummett, Chad M. |
dc.contributor.author |
Abecasis, Gonçalo |
dc.contributor.author |
Mathis, Michael |
dc.contributor.author |
Milewicz, Dianna |
dc.contributor.author |
Body, Simon C. |
dc.contributor.author |
Eriksson, Per |
dc.contributor.author |
Willer, Cristen J. |
dc.contributor.author |
Hveem, Kristian |
dc.contributor.author |
Newton-Cheh, Christopher |
dc.contributor.author |
Smith, J. Gustav |
dc.contributor.author |
Danielsen, Ragnar |
dc.contributor.author |
Thorgeirsson, Gudmundur |
dc.contributor.author |
Thorsteinsdottir, Unnur |
dc.contributor.author |
Gudbjartsson, Daniel |
dc.contributor.author |
Holm, Hilma |
dc.contributor.author |
Stefansson, Kari |
dc.date.accessioned |
2018-06-01T11:34:13Z |
dc.date.available |
2018-06-01T11:34:13Z |
dc.date.issued |
2018-03-07 |
dc.identifier.citation |
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 |
dc.identifier.issn |
2041-1723 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/737 |
dc.description.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. |
dc.description.sponsorship |
This research has been conducted using the UK Biobank Resource under Application Number 15293. We thank all participants of the Cardiovascular Health Improvement Project (CHIP) and BAV registry at the University of Michigan for their contribution to research. We appreciate the valuable efforts from the CHIP and BAV registry collection team. The University of Michigan Health System—Cardiovascular Health Improvement Project was supported by the Frankel Cardiovascular Center. We appreciate the Aikens Fund for Aortic Research (to C.J.W., B.Y.) and McKay research award for supporting this project (to B.Y.). B.Y. is supported by American Association of Thoracic Surgery (AATS) Graham Foundation and Thoracic Surgery Foundation of Research and Education (TSFRE). C.J.W. is supported by HL109946, HL130705, and HL127564. W.Z. is supported by the Rackham Predoctoral Fellowship of the University of Michigan. |
dc.format.extent |
987 |
dc.language.iso |
en |
dc.publisher |
Springer Nature |
dc.relation.ispartofseries |
Nature Communications;9(1) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Congenital heart defects |
dc.subject |
Genome-wide association studies |
dc.subject |
Heart development |
dc.subject |
Valvular disease |
dc.subject |
Blóðrásarsjúkdómar |
dc.subject |
Arfgengi |
dc.subject |
Erfðafræði |
dc.subject |
Erfðarannsóknir |
dc.title |
Genome-wide analysis yields new loci associating with aortic valve stenosis |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
Nature Communications |
dc.identifier.doi |
10.1038/s41467-018-03252-6 |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
Verkfræði- og náttúruvísindasvið (HÍ) |
dc.contributor.school |
School of Engineering and Natural Sciences (UI) |