TY  - JOUR
ID  - enlighten144229
UR  - https://eprints.gla.ac.uk/144229/
IS  - 9
A1  - Villard, Eric
A1  - Perret, Claire
A1  - Gary, Françoise
A1  - Proust, Carole
A1  - Dilanian, Gilles
A1  - Hengstenberg, Christian
A1  - Ruppert, Volker
A1  - Arbustini, Eloisa
A1  - Wichter, Thomas
A1  - Germain, Marine
A1  - Dubourg, Olivier
A1  - Tavazzi, Luigi
A1  - Aumont, Marie-Claude
A1  - DeGroote, Pascal
A1  - Fauchier, Laurent
A1  - Trochu, Jean-Noël
A1  - Gibelin, Pierre
A1  - Aupetit, Jean-François
A1  - Stark, Klaus
A1  - Erdmann, Jeanette
A1  - Hetzer, Roland
A1  - Roberts, Angharad M.
A1  - Barton, Paul J.R.
A1  - Regitz-Zagrosek, Vera
A1  - Aslam, Uzma
A1  - Duboscq-Bidot, Laëtitia
A1  - Meyborg, Matthias
A1  - Maisch, Bernhard
A1  - Madeira, Hugo
A1  - Waldenström, Anders
A1  - Galve, Enrique
A1  - Cleland, John G.
A1  - Dorent, Richard
A1  - Roizes, Gerard
A1  - Zeller, Tanja
A1  - Blankenberg, Stefan
A1  - Goodall, Alison H.
A1  - Cook, Stuart
A1  - Tregouet, David A.
A1  - Tiret, Laurence
A1  - Isnard, Richard
A1  - Komajda, Michel
A1  - Charron, Philippe
A1  - Cambien, François
Y1  - 2011/05//
N2  - Aims: 
Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM.
Methods and results: 
One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P < 5.0 10?7), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p. C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease.
Conclusion: 
This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.
PB  - Oxford University Press
JF  - European Heart Journal
VL  - 32
SN  - 0195-668X
TI  - A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy
SP  - 1065
AV  - none
EP  - 1076
ER  -