10.1371/journal.pgen.1001167 Klaus Stark Klaus Stark Ulrike B. Esslinger Ulrike B. Esslinger Wibke Reinhard Wibke Reinhard George Petrov George Petrov Thomas Winkler Thomas Winkler Michel Komajda Michel Komajda Richard Isnard Richard Isnard Philippe Charron Philippe Charron Eric Villard Eric Villard François Cambien François Cambien Laurence Tiret Laurence Tiret Marie-Claude Aumont Marie-Claude Aumont Olivier Dubourg Olivier Dubourg Jean-Noël Trochu Jean-Noël Trochu Laurent Fauchier Laurent Fauchier Pascal DeGroote Pascal DeGroote Anette Richter Anette Richter Bernhard Maisch Bernhard Maisch Thomas Wichter Thomas Wichter Christa Zollbrecht Christa Zollbrecht Martina Grassl Martina Grassl Heribert Schunkert Heribert Schunkert Patrick Linsel-Nitschke Patrick Linsel-Nitschke Jeanette Erdmann Jeanette Erdmann Jens Baumert Jens Baumert Thomas Illig Thomas Illig Norman Klopp Norman Klopp H.-Erich Wichmann H.-Erich Wichmann Christa Meisinger Christa Meisinger Wolfgang Koenig Wolfgang Koenig Peter Lichtner Peter Lichtner Thomas Meitinger Thomas Meitinger Arne Schillert Arne Schillert Inke R. König Inke R. König Roland Hetzer Roland Hetzer Iris M. Heid Iris M. Heid Vera Regitz-Zagrosek Vera Regitz-Zagrosek Christian Hengstenberg Christian Hengstenberg Genetic Association Study Identifies <em>HSPB7</em> as a Risk Gene for Idiopathic Dilated Cardiomyopathy Public Library of Science 2010 identifies idiopathic dilated cardiomyopathy 2010-10-21 00:16:46 Dataset https://plos.figshare.com/articles/dataset/Genetic_Association_Study_Identifies_HSPB7_as_a_Risk_Gene_for_Idiopathic_Dilated_Cardiomyopathy/141006 <div><p>Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in <em>HSPB7</em> gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06×10<sup>−6</sup>, OR = 0.67 [95% CI 0.57–0.79] for the minor allele T). Three more SNPs showed p < 2.21×10<sup>−5</sup>. <em>De novo</em> genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n = 564, n = 981 controls, p = 2.07×10<sup>−3</sup>, OR = 0.79 [95% CI 0.67–0.92]), France 1 (n = 433 cases, n = 395 controls, p = 3.73×10<sup>−3</sup>, OR = 0.74 [95% CI 0.60–0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26×10<sup>−4</sup>, OR = 0.63 [95% CI 0.50–0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28×10<sup>−13</sup>, OR = 0.72 [95% CI 0.65–0.78]). None of the other three SNPs showed significant results in the replication stage.</p><p>This finding of the <em>HSPB7</em> gene from a genetic search for idiopathic DCM using a large SNP panel underscores the influence of common polymorphisms on DCM susceptibility.</p></div>