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

Journal of Personalized Medicine
Huichun XuStephen B Liggett

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 insigh...Continue Reading

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Citations

Feb 1, 2019·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Jan 30, 2020·Circulation·Salim S ViraniUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
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Methods Mentioned

BETA
genotyping
Assay
exome-sequencing

Software Mentioned

GCTA
SNPTEST
PrediXcan
MESA
Affymetrix Birdseed
IMPUTE2
fastBAT
PLINK
DAVID
SHAPEIT2

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