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Identification of risk loci for primary aldosteronism in genome-wide association studies

Author

Listed:
  • Edith Le Floch

    (Université Paris-Saclay)

  • Teresa Cosentino

    (Université Paris Cité, Inserm, PARCC)

  • Casper K. Larsen

    (Université Paris Cité, Inserm, PARCC)

  • Felix Beuschlein

    (Ludwig-Maximilians-University
    Universitätsspital Zürich (USZ) und Universität Zürich (UZH))

  • Martin Reincke

    (Ludwig-Maximilians-University)

  • Laurence Amar

    (Université Paris Cité, Inserm, PARCC
    Unité Hypertension artérielle)

  • Gian-Paolo Rossi

    (University Hospital)

  • Kelly De Sousa

    (Université Paris Cité, Inserm, PARCC)

  • Stéphanie Baron

    (Université Paris Cité
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie)

  • Sophie Chantalat

    (Université Paris-Saclay)

  • Benjamin Saintpierre

    (Université Paris Cité, Institut Cochin, Genom’IC platform, INSERM, CNRS)

  • Livia Lenzini

    (University Hospital)

  • Arthur Frouin

    (Université Paris-Saclay)

  • Isabelle Giscos-Douriez

    (Université Paris Cité, Inserm, PARCC)

  • Matthis Ferey

    (Université Paris Cité, Inserm, PARCC)

  • Alaa B. Abdellatif

    (Université Paris Cité, Inserm, PARCC)

  • Tchao Meatchi

    (Université Paris Cité, Inserm, PARCC
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service d’Anatomie Pathologique)

  • Jean-Philippe Empana

    (Université Paris Cité, Inserm, PARCC)

  • Xavier Jouven

    (Université Paris Cité, Inserm, PARCC
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Cardiologie)

  • Christian Gieger

    (German Research Center for Environmental Health
    German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Melanie Waldenberger

    (German Research Center for Environmental Health
    German Research Center for Environmental Health
    Partner Site Munich Heart Alliance)

  • Annette Peters

    (German Research Center for Environmental Health
    German Center for Diabetes Research (DZD)
    Partner Site Munich Heart Alliance)

  • Daniele Cusi

    (Institute of Biomedical Technologies National Research Council of Italy
    Bio4Dreams-Business Nursery for Life Sciences)

  • Erika Salvi

    (Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’)

  • Pierre Meneton

    (Sorbonne Université, Université Paris 13)

  • Mathilde Touvier

    (Epidemiology and Statistics Research Center – Université Paris Cité (CRESS))

  • Mélanie Deschasaux

    (Epidemiology and Statistics Research Center – Université Paris Cité (CRESS))

  • Nathalie Druesne-Pecollo

    (Epidemiology and Statistics Research Center – Université Paris Cité (CRESS))

  • Sheerazed Boulkroun

    (Université Paris Cité, Inserm, PARCC)

  • Fabio L. Fernandes-Rosa

    (Université Paris Cité, Inserm, PARCC)

  • Jean-François Deleuze

    (Université Paris-Saclay)

  • Xavier Jeunemaitre

    (Université Paris Cité, Inserm, PARCC
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique)

  • Maria-Christina Zennaro

    (Université Paris Cité, Inserm, PARCC
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique)

Abstract

Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.

Suggested Citation

  • Edith Le Floch & Teresa Cosentino & Casper K. Larsen & Felix Beuschlein & Martin Reincke & Laurence Amar & Gian-Paolo Rossi & Kelly De Sousa & Stéphanie Baron & Sophie Chantalat & Benjamin Saintpierre, 2022. "Identification of risk loci for primary aldosteronism in genome-wide association studies," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32896-8
    DOI: 10.1038/s41467-022-32896-8
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    References listed on IDEAS

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    1. Fumihiko Takeuchi & Masato Akiyama & Nana Matoba & Tomohiro Katsuya & Masahiro Nakatochi & Yasuharu Tabara & Akira Narita & Woei-Yuh Saw & Sanghoon Moon & Cassandra N. Spracklen & Jin-Fang Chai & Youn, 2018. "Interethnic analyses of blood pressure loci in populations of East Asian and European descent," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Matthieu Santos & Stéphanie Backer & Benjamin Saintpierre & Brigitte Izac & Muriel Andrieu & Franck Letourneur & Frederic Relaix & Athanassia Sotiropoulos & Pascal Maire, 2020. "Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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