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GWAS Study

Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience.

Jurgens SJ, Rämö JT, Kramarenko DR et al.

39572784 PubMed ID
GWAS Study Type
2404278 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

JS
Jurgens SJ
RJ
Rämö JT
KD
Kramarenko DR
WL
Wijdeveld LFJM
HJ
Haas J
CM
Chaffin MD
GS
Garnier S
GL
Gaziano L
WL
Weng LC
LA
Lipov A
ZS
Zheng SL
HA
Henry A
HJ
Huffman JE
CS
Challa S
RF
Rühle F
VC
Verdugo CD
KJ
Krijger Juárez C
KS
Kany S
VO
van Orsouw CA
BK
Biddinger K
PE
Poel E
EA
Elliott AL
WX
Wang X
FC
Francis C
RR
Ruan R
KS
Koyama S
BL
Beekman L
ZD
Zimmerman DS
DJ
Deleuze JF
VE
Villard E
TD
Trégouët DA
IR
Isnard R
BD
Boomsma DI
DG
de Geus EJC
TR
Tadros R
PY
Pinto YM
WA
Wilde AAM
HJ
Hottenga JJ
SJ
Sinisalo J
NT
Niiranen T
WR
Walsh R
SA
Schmidt AF
CS
Choi SH
CK
Chang KM
TP
Tsao PS
MP
Matthews PM
WJ
Ware JS
LR
Lumbers RT
VD
van der Crabben S
LJ
Laukkanen J
PA
Palotie A
AA
Amin AS
CP
Charron P
MB
Meder B
EP
Ellinor PT
DM
Daly M
AK
Aragam KG
BC
Bezzina CR
Chapter II

Abstract

Summary of the research findings

Dilated cardiomyopathy (DCM) is a heart muscle disease that represents an important cause of morbidity and mortality, yet causal mechanisms remain largely elusive. Here, we perform a large-scale genome-wide association study and multitrait analysis for DCM using 9,365 cases and 946,368 controls. We identify 70 genome-wide significant loci, which show broad replication in independent samples and map to 63 prioritized genes. Tissue, cell type and pathway enrichment analyses highlight the central role of the cardiomyocyte and contractile apparatus in DCM pathogenesis. Polygenic risk scores constructed from our genome-wide association study predict DCM across different ancestry groups, show differing contributions to DCM depending on rare pathogenic variant status and associate with systolic heart failure across various clinical settings. Mendelian randomization analyses reveal actionable potential causes of DCM, including higher bodyweight and higher systolic blood pressure. Our findings provide insights into the genetic architecture and mechanisms underlying DCM and myocardial function more broadly.

9,365 European or unknown ancestry cases, 946,368 European or unknown ancestry controls

Chapter III

Study Statistics

Key metrics and study information

2404278
Total Participants
GWAS
Study Type
Yes
Replicated
13,258 European, African, Admixed American or unknown ancestry cases, 1,435,287 European, African, Admixed American or unknown ancestry controls
Replication Participants
European, NR, European, African unspecified, Hispanic or Latin American, NR
Ancestry
Netherlands, U.S., Finland, Italy, U.K., Germany
Recruitment Country
Chapter IV

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