title: Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.
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.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Jamie
authors.initials: J
authors.lastname: Bentham
authors.forename: Ana
authors.initials: A
authors.lastname: Topf
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenika
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Chrysovalanto
authors.initials: C
authors.lastname: Mamasoula
authors.forename: Catherine
authors.initials: C
authors.lastname: Cosgrove
authors.forename: Gillian
authors.initials: G
authors.lastname: Blue
authors.forename: Javier
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authors.lastname: Granados-Riveron
authors.forename: Kerry
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authors.lastname: Setchfield
authors.forename: Chris
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authors.lastname: Thornborough
authors.forename: Jeroen
authors.initials: J
authors.lastname: Breckpot
authors.forename: Rachel
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authors.lastname: Soemedi
authors.forename: Ruairidh
authors.initials: R
authors.lastname: Martin
authors.forename: Thahira J
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authors.lastname: Rahman
authors.forename: Darroch
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authors.lastname: Hall
authors.forename: Klaartje
authors.initials: K
authors.lastname: van Engelen
authors.forename: Antoon F M
authors.initials: AF
authors.lastname: Moorman
authors.forename: Aelko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Phil
authors.initials: P
authors.lastname: Barnett
authors.forename: Tamara T
authors.initials: TT
authors.lastname: Koopmann
authors.forename: Michiel E
authors.initials: ME
authors.lastname: Adriaens
authors.forename: Andras
authors.initials: A
authors.lastname: Varro
authors.forename: Alfred L
authors.initials: AL
authors.lastname: George
authors.forename: Christobal
authors.initials: C
authors.lastname: dos Remedios
authors.forename: Nanette H
authors.initials: NH
authors.lastname: Bishopric
authors.forename: Connie R
authors.initials: CR
authors.lastname: Bezzina
authors.forename: John
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: Marc
authors.initials: M
authors.lastname: Gewillig
authors.forename: Frances A
authors.initials: FA
authors.lastname: Bu'Lock
authors.forename: David
authors.initials: D
authors.lastname: Winlaw
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: J David
authors.initials: JD
authors.lastname: Brook
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Mulder
authors.forename: Seema
authors.initials: S
authors.lastname: Mital
authors.forename: Alex V
authors.initials: AV
authors.lastname: Postma
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Judith A
authors.initials: JA
authors.lastname: Goodship
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Keavney
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics*; D006331:Heart Diseases / Q000151:congenital / Q000235:genetics*; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D010641:Phenotype