Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.

Journal article

We carried out a genome-wide association study (GWAS) of congenital heart disease (CHD). Our discovery cohort comprised 1,995 CHD cases and 5,159 controls and included affected individuals from each of the 3 major clinical CHD categories (with septal, obstructive and cyanotic defects). When all CHD phenotypes were considered together, no region achieved genome-wide significant association. However, a region on chromosome 4p16, adjacent to the MSX1 and STX18 genes, was associated (P = 9.5 × 10⁻⁷) with the risk of ostium secundum atrial septal defect (ASD) in the discovery cohort (N = 340 cases), and this association was replicated in a further 417 ASD cases and 2,520 controls (replication P = 5.0 × 10⁻⁵; odds ratio (OR) in replication cohort = 1.40, 95% confidence interval (CI) = 1.19-1.65; combined P = 2.6 × 10⁻¹⁰). Genotype accounted for ~9% of the population-attributable risk of ASD.

Authors: Cordell, H; Bentham, J; Topf, A; Zelenika, D; Heath, S

• Publication status: Published
• Journal: Nature genetics
• Volume: 45
• Issue: 7
• Pages: 822-824
• Publication date: 2013-07-01
• DOI: 10.1038/ng.2637
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Heart Septal Defects, Atrial; Humans; Genotype; Animals; Genetic Predisposition to Disease; Female; Male; Cohort Studies; Abnormalities, Multiple; Case-Control Studies; Heart Diseases; Mice; Genome-Wide Association Study; Chromosomes, Human, Pair 4; Phenotype; Genetic Loci; Heart Defects, Congenital