A genome-wide association study of idiopathic dilated cardiomyopathy in African Americans

Huichun Xu, Gerald W. Dorn, Amol Shetty, Ankita Parihar, Tushar Dave, Shawn W. Robinson, Stephen S. Gottlieb, Mark P. Donahue, Gordon F. Tomaselli, William E. Kraus, Braxton D. Mitchell, Stephen B. Liggett

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number11
JournalJournal of Personalized Medicine
Volume8
Issue number1
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Dilated Cardiomyopathy
African Americans
Genes
Calcium Signaling
Gap Junctions
Calcium Channels
Muscle Contraction
Ethnic Groups
Intercellular Signaling Peptides and Proteins
Myocardium
Heart Failure
Genome
Confidence Intervals

Keywords

  • African American
  • CACNB4
  • Calcium channel
  • GWAS
  • Heart failure
  • Idiopathic dilated cardiomyopathy

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Xu, H., Dorn, G. W., Shetty, A., Parihar, A., Dave, T., Robinson, S. W., ... Liggett, S. B. (2018). A genome-wide association study of idiopathic dilated cardiomyopathy in African Americans. Journal of Personalized Medicine, 8(1), [11]. https://doi.org/10.3390/jpm8010011

A genome-wide association study of idiopathic dilated cardiomyopathy in African Americans. / Xu, Huichun; Dorn, Gerald W.; Shetty, Amol; Parihar, Ankita; Dave, Tushar; Robinson, Shawn W.; Gottlieb, Stephen S.; Donahue, Mark P.; Tomaselli, Gordon F.; Kraus, William E.; Mitchell, Braxton D.; Liggett, Stephen B.

In: Journal of Personalized Medicine, Vol. 8, No. 1, 11, 01.03.2018.

Research output: Contribution to journalArticle

Xu, H, Dorn, GW, Shetty, A, Parihar, A, Dave, T, Robinson, SW, Gottlieb, SS, Donahue, MP, Tomaselli, GF, Kraus, WE, Mitchell, BD & Liggett, SB 2018, 'A genome-wide association study of idiopathic dilated cardiomyopathy in African Americans', Journal of Personalized Medicine, vol. 8, no. 1, 11. https://doi.org/10.3390/jpm8010011
Xu, Huichun ; Dorn, Gerald W. ; Shetty, Amol ; Parihar, Ankita ; Dave, Tushar ; Robinson, Shawn W. ; Gottlieb, Stephen S. ; Donahue, Mark P. ; Tomaselli, Gordon F. ; Kraus, William E. ; Mitchell, Braxton D. ; Liggett, Stephen B. / A genome-wide association study of idiopathic dilated cardiomyopathy in African Americans. In: Journal of Personalized Medicine. 2018 ; Vol. 8, No. 1.
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