Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects

on behalf of the Pediatric Cardiac Genomics Consortium¶

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects.

Original languageEnglish (US)
Article numbere0219926
JournalPloS one
Volume14
Issue number7
DOIs
StatePublished - Jan 1 2019

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Genome-Wide Association Study
Meta-Analysis
Genes
heart
Association reactions
Defects
genes
Congenital Heart Defects
Eukaryotic Initiation Factor-4E
Microarray Analysis
genome-wide association study
Chromatin
Microarrays
Genome
RNA
chromatin
testing
genome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. / on behalf of the Pediatric Cardiac Genomics Consortium¶.

In: PloS one, Vol. 14, No. 7, e0219926, 01.01.2019.

Research output: Contribution to journalArticle

on behalf of the Pediatric Cardiac Genomics Consortium¶ 2019, 'Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects', PloS one, vol. 14, no. 7, e0219926. https://doi.org/10.1371/journal.pone.0219926
on behalf of the Pediatric Cardiac Genomics Consortium¶. / Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. In: PloS one. 2019 ; Vol. 14, No. 7.
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