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GWAS Study

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

Le Floch E, Cosentino T, Larsen CK et al.

36057693 PubMed ID
GWAS Study Type
4458 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

LF
Le Floch E
CT
Cosentino T
LC
Larsen CK
BF
Beuschlein F
RM
Reincke M
AL
Amar L
RG
Rossi GP
DS
De Sousa K
BS
Baron S
CS
Chantalat S
SB
Saintpierre B
LL
Lenzini L
FA
Frouin A
GI
Giscos-Douriez I
FM
Ferey M
AA
Abdellatif AB
MT
Meatchi T
EJ
Empana JP
JX
Jouven X
GC
Gieger C
WM
Waldenberger M
PA
Peters A
CD
Cusi D
SE
Salvi E
MP
Meneton P
TM
Touvier M
DM
Deschasaux M
DN
Druesne-Pecollo N
BS
Boulkroun S
FF
Fernandes-Rosa FL
DJ
Deleuze JF
JX
Jeunemaitre X
ZM
Zennaro MC
Chapter II

Abstract

Summary of the research findings

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.

562 European ancestry cases, 950 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

4458
Total Participants
GWAS
Study Type
Yes
Replicated
600 European ancestry cases, 2,346 European ancestry controls
Replication Participants
European
Ancestry
France, Italy, Germany
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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