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

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



  • 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
Issue number1
Number of pages10
Publication statusPublished - 2018

Bibliographical note

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