Key result
Novel CACNB4 variant linked to ~51% lower risk of idiopathic DCM in African Americans.
Why the study?
Does the CACNB4 gene variant rs150793926 increase susceptibility to idiopathic dilated cardiomyopathy in African Americans?
Case-Control (n=1,829)
Yes
Does the CACNB4 gene variant rs150793926 increase susceptibility to idiopathic dilated cardiomyopathy in African Americans?
Odds Ratio: 0.49
p-value: p=4.1 × 10−8
This first GWAS of idiopathic dilated cardiomyopathy in African Americans identifies a novel susceptibility locus in the CACNB4 gene, highlighting the importance of diverse genetic studies.
Association with CACNB4 variant in African Americans with IDC is hypothesis-generating; extends prior Caucasian GWAS findings but requires validation before clinical use.
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.
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Xu et al. (2018) conducted a case-control in Idiopathic Dilated Cardiomyopathy (n=1,829). CACNB4 gene variant rs150793926 vs. Controls without idiopathic dilated cardiomyopathy was evaluated on Genome-wide association with idiopathic dilated cardiomyopathy (OR 0.49, p=4.1 × 10−8). A novel intronic variant in the CACNB4 gene (rs150793926) was significantly associated with idiopathic dilated cardiomyopathy in African Americans (OR 0.49, p = 4.1 × 10−8).
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