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

Author

Listed:
  • Anna Helgadottir

    (deCODE genetics/Amgen Inc.)

  • Gudmar Thorleifsson

    (deCODE genetics/Amgen Inc.)

  • Solveig Gretarsdottir

    (deCODE genetics/Amgen Inc.)

  • Olafur A. Stefansson

    (deCODE genetics/Amgen Inc.)

  • Vinicius Tragante

    (deCODE genetics/Amgen Inc.)

  • Rosa B. Thorolfsdottir

    (deCODE genetics/Amgen Inc.)

  • Ingileif Jonsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Thorsteinn Bjornsson

    (deCODE genetics/Amgen Inc.)

  • Valgerdur Steinthorsdottir

    (deCODE genetics/Amgen Inc.)

  • Niek Verweij

    (University Medical Center Groningen
    Broad Institute of MIT and Harvard)

  • Jonas B. Nielsen

    (University of Michigan)

  • Wei Zhou

    (University of Michigan)

  • Lasse Folkersen

    (Karolinska University Hospital Solna, Karolinska Institutet
    Technical University of Denmark)

  • Andreas Martinsson

    (Lund University and Skåne University Hospital)

  • Mahyar Heydarpour

    (Brigham and Women’s Hospital, 75 Francis Street)

  • Siddharth Prakash

    (University of Texas Health Science Center at Houston)

  • Gylfi Oskarsson

    (Landspitali National University Hospital of Iceland)

  • Tomas Gudbjartsson

    (Landspitali National University Hospital)

  • Arnar Geirsson

    (Yale University School of Medicine)

  • Isleifur Olafsson

    (Landspitali National University Hospital)

  • Emil L. Sigurdsson

    (Heilsugaeslan Solvangi
    University of Iceland)

  • Peter Almgren

    (Lund University
    Skåne University Hospital)

  • Olle Melander

    (Lund University
    Skåne University Hospital)

  • Anders Franco-Cereceda

    (Karolinska University Hospital Solna, Karolinska Institutet)

  • Anders Hamsten

    (Karolinska University Hospital Solna, Karolinska Institutet)

  • Lars Fritsche

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Maoxuan Lin

    (University of Michigan)

  • Bo Yang

    (University of Michigan
    University of Michigan)

  • Whitney Hornsby

    (University of Michigan)

  • Dongchuan Guo

    (University of Texas Health Science Center at Houston)

  • Chad M. Brummett

    (University of Michigan)

  • Gonçalo Abecasis

    (University of Michigan)

  • Michael Mathis

    (University of Michigan)

  • Dianna Milewicz

    (University of Texas Health Science Center at Houston
    St. Luke’s Episcopal Hospital)

  • Simon C. Body

    (Brigham and Women’s Hospital, 75 Francis Street)

  • Per Eriksson

    (Karolinska University Hospital Solna, Karolinska Institutet)

  • Cristen J. Willer

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

  • Kristian Hveem

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Christopher Newton-Cheh

    (Broad Institute of MIT and Harvard
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • J. Gustav Smith

    (Lund University and Skåne University Hospital)

  • Ragnar Danielsen

    (University of Iceland
    Landspitali National University Hospital of Iceland)

  • Gudmundur Thorgeirsson

    (deCODE genetics/Amgen Inc.
    University of Iceland
    Landspitali National University Hospital of Iceland)

  • Unnur Thorsteinsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Hilma Holm

    (deCODE genetics/Amgen Inc.)

  • Kari Stefansson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

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.

Suggested Citation

  • Anna Helgadottir & Gudmar Thorleifsson & Solveig Gretarsdottir & Olafur A. Stefansson & Vinicius Tragante & Rosa B. Thorolfsdottir & Ingileif Jonsdottir & Thorsteinn Bjornsson & Valgerdur Steinthorsdo, 2018. "Genome-wide analysis yields new loci associating with aortic valve stenosis," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03252-6
    DOI: 10.1038/s41467-018-03252-6
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    Cited by:

    1. Pengfei Lu & Ping Wang & Bingruo Wu & Yidong Wang & Yang Liu & Wei Cheng & Xuhui Feng & Xinchun Yuan & Miriam M. Atteya & Haleigh Ferro & Yukiko Sugi & Grant Rydquist & Mahdi Esmaily & Jonathan T. But, 2022. "A SOX17-PDGFB signaling axis regulates aortic root development," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Sébastien Thériault & Zhonglin Li & Erik Abner & Jian’an Luan & Hasanga D. Manikpurage & Ursula Houessou & Pardis Zamani & Mewen Briend & Dominique K. Boudreau & Nathalie Gaudreault & Lily Frenette & , 2024. "Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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