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

Lookup NU author(s): Professor Heather Cordell, Dr Ana TopfORCiD, Valentina Mamasoula, Dr Rebecca Darlay, Rachel Soemedi, Dr Ian Wilson, Dr Kristin Ayers, Dr Thahira Rahman, Dr Darroch Hall, Dr John O'Sullivan, Professor Bernard Keavney, Professor Judith Goodship



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.

Publication metadata

Author(s): Cordell HJ, Topf A, Mamasoula C, Postma AV, Bentham J, Zelenika D, Heath S, Blue G, Cosgrove C, Riveron JG, Darlay R, Soemedi R, Wilson IJ, Ayers KL, Rahman TJ, Hall D, Mulder BJM, Zwinderman AH, van Engelen K, Brook JD, Setchfield K, Bu'Lock FA, Thornborough C, O'Sullivan J, Stuart AG, Parsons J, Bhattacharya S, Winlaw D, Mital S, Gewillig M, Breckpot J, Devriendt K, Moorman AFM, Rauch A, Lathrop GM, Keavney BD, Goodship JA

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2013

Volume: 22

Issue: 7

Pages: 1473-1481

Print publication date: 07/01/2013

Date deposited: 24/06/2013

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/dds552


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Funder referenceFunder name
Canadian Foundation for Innovation
Heart and Stroke Foundation of Ontario
Labatt Family Heart Centre
National Eye Institute via an NIH/CIDR genotyping project (
National Institute for Health Research, through the Northumberland, Tyne and Wear CLRN
British Heart Foundation
McLaughlin Centre
Ontario Ministry of Research and Innovation
085475Wellcome Trust
087436Wellcome Trust
HEALTH-F2-2008-223040European Community
HEALTH-F4-2007-201413 ENGAGEEuropean Community
HEALTH-F2-2008-201865 GEFOSEuropean Community