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A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis

Author

Listed:
  • Sébastien Thériault

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
    Laval University)

  • Nathalie Gaudreault

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Maxime Lamontagne

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Mickael Rosa

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Marie-Chloé Boulanger

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • David Messika-Zeitoun

    (Bichat Hospital
    INSERM U698 and University Paris 7)

  • Marie-Annick Clavel

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Romain Capoulade

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • François Dagenais

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Philippe Pibarot

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Patrick Mathieu

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval)

  • Yohan Bossé

    (Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
    Laval University)

Abstract

Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease and the current treatment options cannot stop or delay its progression. A GWAS on 1009 cases and 1017 ethnically matched controls was combined with a large-scale eQTL mapping study of human aortic valve tissues (n = 233) to identify susceptibility genes for CAVS. Replication was performed in the UK Biobank, including 1391 cases and 352,195 controls. A transcriptome-wide association study (TWAS) reveals PALMD (palmdelphin) as significantly associated with CAVS. The CAVS risk alleles and increasing disease severity are both associated with decreased mRNA expression levels of PALMD in valve tissues. The top variant identified shows a similar effect and strong association with CAVS (P = 1.53 × 10−10) in UK Biobank. The identification of PALMD as a susceptibility gene for CAVS provides insights into the genetic nature of this disease, opens avenues to investigate its etiology and to develop much-needed therapeutic options.

Suggested Citation

  • Sébastien Thériault & Nathalie Gaudreault & Maxime Lamontagne & Mickael Rosa & Marie-Chloé Boulanger & David Messika-Zeitoun & Marie-Annick Clavel & Romain Capoulade & François Dagenais & Philippe Pib, 2018. "A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03260-6
    DOI: 10.1038/s41467-018-03260-6
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    Cited by:

    1. Kevin L Keys & Angel C Y Mak & Marquitta J White & Walter L Eckalbar & Andrew W Dahl & Joel Mefford & Anna V Mikhaylova & María G Contreras & Jennifer R Elhawary & Celeste Eng & Donglei Hu & Scott Hun, 2020. "On the cross-population generalizability of gene expression prediction models," PLOS Genetics, Public Library of Science, vol. 16(8), pages 1-28, August.

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