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

Heather J Cordell, Jamie Bentham, Ana Topf, Diana Zelenika, Simon Heath, Chrysovalanto Mamasoula, Catherine Cosgrove, Gillian Blue, Javier Granados-Riveron, Kerry Setchfield, Chris Thornborough, Jeroen Breckpot, Rachel Soemedi, Ruairidh Martin, Thahira J Rahman, Darroch Hall, Klaartje van Engelen, Antoon F Moorman, Aelko H Zwinderman, Phil BarnettTamara T Koopmann, Michiel E Adriaens, Andras Varro, Alfred L George, Christobal dos Remedios, Nanette H Bishopric, Connie R Bezzina, John O'Sullivan, Marc Gewillig, Frances A Bu'Lock, David Winlaw, Shoumo Bhattacharya, Koen Devriendt, JD Brook, Barbara J Mulder, Seema Mital, Alex V Postma, GM Lathrop, Martin Farrall, Judith A Goodship, Bernard D Keavney

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Abstract

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.
Original languageEnglish
Pages (from-to)822-824
Number of pages3
JournalNature Genetics
Volume45
Issue number7
DOIs
Publication statusPublished - 2013

Cite this

Cordell, H. J., Bentham, J., Topf, A., Zelenika, D., Heath, S., Mamasoula, C., Cosgrove, C., Blue, G., Granados-Riveron, J., Setchfield, K., Thornborough, C., Breckpot, J., Soemedi, R., Martin, R., Rahman, T. J., Hall, D., van Engelen, K., Moorman, A. F., Zwinderman, A. H., ... Keavney, B. D. (2013). Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Nature Genetics, 45(7), 822-824. https://doi.org/10.1038/ng.2637