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.M. 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, J. David Brook, Barbara J.M. Mulder, Seema Mital, Alex V. Postma, G. Mark Lathrop, Martin Farrall, Judith A. Goodship*, Bernard D. Keavney

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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
Issue number7
Publication statusPublished - Jul 2013

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