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 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

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)822-824
Number of pages3
JournalNature Genetics
Volume45
Issue number7
DOIs
StatePublished - Jul 1 2013

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Atrial Heart Septal Defects
Genome-Wide Association Study
Heart Diseases
Chromosomes
Phenotype
Odds Ratio
Genotype
Genome
Confidence Intervals
Population
Genes

ASJC Scopus subject areas

  • Genetics

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Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. / Cordell, Heather J.; Bentham, Jamie; Topf, Ana; Zelenika, Diana; Heath, Simon; Mamasoula, Chrysovalanto; Cosgrove, Catherine; Blue, Gillian; Granados-Riveron, Javier; Setchfield, Kerry; Thornborough, Chris; Breckpot, Jeroen; Soemedi, Rachel; Martin, Ruairidh; Rahman, Thahira J.; Hall, Darroch; Van Engelen, Klaartje; Moorman, Antoon F M; Zwinderman, Aelko H.; Barnett, Phil; Koopmann, Tamara T.; Adriaens, Michiel E.; Varro, Andras; George, Alfred L.; Dos Remedios, Christobal; Bishopric, Nanette; Bezzina, Connie R.; O'Sullivan, John; Gewillig, Marc; Bu'Lock, Frances A.; Winlaw, David; Bhattacharya, Shoumo; Devriendt, Koen; Brook, J. David; Mulder, Barbara J M; Mital, Seema; Postma, Alex V.; Lathrop, G. Mark; Farrall, Martin; Goodship, Judith A.; Keavney, Bernard D.

In: Nature Genetics, Vol. 45, No. 7, 01.07.2013, p. 822-824.

Research output: Contribution to journalArticle

Cordell, HJ, Bentham, J, Topf, A, Zelenika, D, Heath, S, Mamasoula, C, Cosgrove, C, Blue, G, Granados-Riveron, J, Setchfield, K, Thornborough, C, Breckpot, J, Soemedi, R, Martin, R, Rahman, TJ, Hall, D, Van Engelen, K, Moorman, AFM, Zwinderman, AH, Barnett, P, Koopmann, TT, Adriaens, ME, Varro, A, George, AL, Dos Remedios, C, Bishopric, N, Bezzina, CR, O'Sullivan, J, Gewillig, M, Bu'Lock, FA, Winlaw, D, Bhattacharya, S, Devriendt, K, Brook, JD, Mulder, BJM, Mital, S, Postma, AV, Lathrop, GM, Farrall, M, Goodship, JA & Keavney, BD 2013, 'Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16', Nature Genetics, vol. 45, no. 7, pp. 822-824. https://doi.org/10.1038/ng.2637
Cordell, Heather J. ; Bentham, Jamie ; Topf, Ana ; Zelenika, Diana ; Heath, Simon ; Mamasoula, Chrysovalanto ; Cosgrove, Catherine ; Blue, Gillian ; Granados-Riveron, Javier ; Setchfield, Kerry ; Thornborough, Chris ; Breckpot, Jeroen ; Soemedi, Rachel ; Martin, Ruairidh ; Rahman, Thahira J. ; Hall, Darroch ; Van Engelen, Klaartje ; Moorman, Antoon F M ; Zwinderman, Aelko H. ; Barnett, Phil ; Koopmann, Tamara T. ; Adriaens, Michiel E. ; Varro, Andras ; George, Alfred L. ; Dos Remedios, Christobal ; Bishopric, Nanette ; Bezzina, Connie R. ; O'Sullivan, John ; Gewillig, Marc ; Bu'Lock, Frances A. ; Winlaw, David ; Bhattacharya, Shoumo ; Devriendt, Koen ; Brook, J. David ; Mulder, Barbara J M ; Mital, Seema ; Postma, Alex V. ; Lathrop, G. Mark ; Farrall, Martin ; Goodship, Judith A. ; Keavney, Bernard D. / Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. In: Nature Genetics. 2013 ; Vol. 45, No. 7. pp. 822-824.
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AU - Cordell, Heather J.

AU - Bentham, Jamie

AU - Topf, Ana

AU - Zelenika, Diana

AU - Heath, Simon

AU - Mamasoula, Chrysovalanto

AU - Cosgrove, Catherine

AU - Blue, Gillian

AU - Granados-Riveron, Javier

AU - Setchfield, Kerry

AU - Thornborough, Chris

AU - Breckpot, Jeroen

AU - Soemedi, Rachel

AU - Martin, Ruairidh

AU - Rahman, Thahira J.

AU - Hall, Darroch

AU - Van Engelen, Klaartje

AU - Moorman, Antoon F M

AU - Zwinderman, Aelko H.

AU - Barnett, Phil

AU - Koopmann, Tamara T.

AU - Adriaens, Michiel E.

AU - Varro, Andras

AU - George, Alfred L.

AU - Dos Remedios, Christobal

AU - Bishopric, Nanette

AU - Bezzina, Connie R.

AU - O'Sullivan, John

AU - Gewillig, Marc

AU - Bu'Lock, Frances A.

AU - Winlaw, David

AU - Bhattacharya, Shoumo

AU - Devriendt, Koen

AU - Brook, J. David

AU - Mulder, Barbara J M

AU - Mital, Seema

AU - Postma, Alex V.

AU - Lathrop, G. Mark

AU - Farrall, Martin

AU - Goodship, Judith A.

AU - Keavney, Bernard D.

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