title: Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.
abstract: 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.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Ana
authors.initials: A
authors.lastname: Töpf
authors.forename: Chrysovalanto
authors.initials: C
authors.lastname: Mamasoula
authors.forename: Alex V
authors.initials: AV
authors.lastname: Postma
authors.forename: Jamie
authors.initials: J
authors.lastname: Bentham
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenika
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Gillian
authors.initials: G
authors.lastname: Blue
authors.forename: Catherine
authors.initials: C
authors.lastname: Cosgrove
authors.forename: Javier
authors.initials: J
authors.lastname: Granados Riveron
authors.forename: Rebecca
authors.initials: R
authors.lastname: Darlay
authors.forename: Rachel
authors.initials: R
authors.lastname: Soemedi
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Wilson
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Ayers
authors.forename: Thahira J
authors.initials: TJ
authors.lastname: Rahman
authors.forename: Darroch
authors.initials: D
authors.lastname: Hall
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Mulder
authors.forename: Aelko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Klaartje
authors.initials: K
authors.lastname: van Engelen
authors.forename: J David
authors.initials: JD
authors.lastname: Brook
authors.forename: Kerry
authors.initials: K
authors.lastname: Setchfield
authors.forename: Frances A
authors.initials: FA
authors.lastname: Bu'Lock
authors.forename: Chris
authors.initials: C
authors.lastname: Thornborough
authors.forename: John
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: A Graham
authors.initials: AG
authors.lastname: Stuart
authors.forename: Jonathan
authors.initials: J
authors.lastname: Parsons
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: David
authors.initials: D
authors.lastname: Winlaw
authors.forename: Seema
authors.initials: S
authors.lastname: Mital
authors.forename: Marc
authors.initials: M
authors.lastname: Gewillig
authors.forename: Jeroen
authors.initials: J
authors.lastname: Breckpot
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Antoon F M
authors.initials: AF
authors.lastname: Moorman
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Keavney
authors.forename: Judith A
authors.initials: JA
authors.lastname: Goodship
mesh_terms: D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013771:Tetralogy of Fallot / Q000235:genetics*