Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

Heather J. Cordell, Ana Töpf, Chrysovalanto Mamasoula, Alex V. Postma, Jamie Bentham, Diana Zelenika, Simon Heath, Gillian Blue, Catherine Cosgrove, Javier Granados riveron, Rebecca Darlay, Rachel Soemedi, Ian J. Wilson, Kristin L. Ayers, Thahira J. Rahman, Darroch Hall, Barbara J.M. Mulder, Aelko H. Zwinderman, Klaartje Van engelen, J. David BrookKerry Setchfield, Frances A. Bu'lock, Chris Thornborough, John O'sullivan, A. Graham Stuart, Jonathan Parsons, Shoumo Bhattacharya, David Winlaw, Seema Mital, Marc Gewillig, Jeroen Breckpot, Koen Devriendt, Antoon F.M. Moorman, Anita Rauch, G. Mark Lathrop, Bernard D. Keavney*, Judith A. Goodship

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10-7) and replicated convincingly (P = 3.9 × 10-5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10-11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10-7) and replicated convincingly (P = 1.2 × 10-5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10-11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.

Original languageEnglish
Article numberdds552
Pages (from-to)1473-1481
Number of pages9
JournalHuman Molecular Genetics
Issue number7
Publication statusPublished - Apr 2013

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