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J. Pers. Med. 2018, 8(1), 11; https://doi.org/10.3390/jpm8010011

A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans

1
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2
Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
3
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4
Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
5
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27708, USA
6
Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD 21218, USA
7
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA
8
Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA
9
Department of Internal Medicine and Molecular Pharmacology and Physiology, and the Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA; For the Genetics of African American Heart Failure (GAAHF) Consortium
*
Authors to whom correspondence should be addressed.
Received: 22 November 2017 / Revised: 17 February 2018 / Accepted: 21 February 2018 / Published: 26 February 2018
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Abstract

Idiopathic dilated cardiomyopathy (IDC) is the most common form of non-ischemic chronic heart failure. Despite the higher prevalence of IDC in African Americans, the genetics of IDC have been relatively understudied in this ethnic group. We performed a genome-wide association study to identify susceptibility genes for IDC in African Americans recruited from five sites in the U.S. (662 unrelated cases and 1167 controls). The heritability of IDC was calculated to be 33% (95% confidence interval: 19–47%; p = 6.4 × 10−7). We detected association of a variant in a novel intronic locus in the CACNB4 gene meeting genome-wide levels of significance (p = 4.1 × 10−8). The CACNB4 gene encodes a calcium channel subunit expressed in the heart that is important for cardiac muscle contraction. This variant has not previously been associated with IDC in any racial group. Pathway analysis, based on the 1000 genes most strongly associated with IDC, showed an enrichment for genes related to calcium signaling, growth factor signaling, neuronal/neuromuscular signaling, and various types of cellular level signaling, including gap junction and cAMP signaling. Our results suggest a novel locus for IDC in African Americans and provide additional insights into the genetic architecture and etiology. View Full-Text
Keywords: idiopathic dilated cardiomyopathy; GWAS; CACNB4; calcium channel; African American; heart failure idiopathic dilated cardiomyopathy; GWAS; CACNB4; calcium channel; African American; heart failure
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Xu, H.; Dorn II, G.W.; Shetty, A.; Parihar, A.; Dave, T.; Robinson, S.W.; Gottlieb, S.S.; Donahue, M.P.; Tomaselli, G.F.; Kraus, W.E.; Mitchell, B.D.; Liggett, S.B. A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans. J. Pers. Med. 2018, 8, 11.

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