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

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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  • Author: Helgadottir, Anna

    Amgen Incorporated, Iceland

  • Author: Thorleifsson, Gudmar

    Amgen Incorporated, Iceland

  • Author: Gretarsdottir, Solveig

    Amgen Incorporated, Iceland

  • Author: Stefansson, Olafur A.

    Amgen Incorporated, Iceland

  • Author: Tragante, Vinicius

    Amgen Incorporated, Iceland

  • Author: Thorolfsdottir, Rosa B.

    Amgen Incorporated, Iceland

  • Author: Jonsdottir, Ingileif

    Amgen Incorporated, Iceland

  • Author: Bjornsson, Thorsteinn

    Amgen Incorporated, Iceland

  • Author: Steinthorsdottir, Valgerdur

    Amgen Incorporated, Iceland

  • Author: Verweij, Niek

    University of Groningen, Netherlands

  • Author: Nielsen, Jonas B.

    University of Michigan, Ann Arbor, United States

  • Author: Zhou, Wei-Wu

    University of Michigan, Ann Arbor, United States

  • Author: Folkersen, Lasse Westergaard

    Integrative Systems Biology, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Martinsson, Andreas

  • Author: Heydarpour, Mahyar

  • Author: Prakash, Siddharth

  • Author: Oskarsson, Gylfi

  • Author: Gudbjartsson, Tomas

  • Author: Geirsson, Arnar

  • Author: Olafsson, Isleifur

  • Author: Sigurdsson, Emil L.

  • Author: Almgren, Peter

  • Author: Melander, Olle

  • Author: Franco-Cereceda, Anders

  • Author: Hamsten, Anders

  • Author: Fritsche, Lars

  • Author: Lin, Maoxuan

  • Author: Yang, Bo

  • Author: Hornsby, Whitney

  • Author: Guo, Dongchuan

  • Author: Brummett, Chad M.

  • Author: Abecasis, Goncalo R.

  • Author: Mathis, Michael R.

  • Author: Milewicz, Dianna M.

  • Author: Body, Simon C.

  • Author: Eriksson, Per

  • Author: Willer, Cristen J.

  • Author: Hveem, Kristian

  • Author: Newton-Cheh, Christopher

  • Author: Smith, J Gustav

  • Author: Danielsen, Ragnar

    University of Iceland, Iceland

  • Author: Thorgeirsson, Gudmundur

    Amgen Incorporated, Iceland

  • Author: Thorsteinsdottir, Unnur

    Amgen Incorporated, Iceland

  • Author: Gudbjartsson, Daniel F.

    Amgen Incorporated, Iceland

  • Author: Holm, Hilma

    Amgen Incorporated, Iceland

  • Author: Stefansson, Kari

    Amgen Incorporated, Iceland

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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 x 10(-22)) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 x 10(-13)). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 x 10(-10)) and aortic root diameter (P = 1.30 x 10(-8)), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 x 10(-3)) and coronary artery disease (OR = 1.05, P = 9.3 x 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.
Original languageEnglish
Article number987
JournalNature Communications
Volume9
Issue number1
Number of pages10
ISSN2041-1723
DOIs
Publication statusPublished - 2018

Bibliographical note

Open Access 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 hold. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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