Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.: 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 Moorman; Aelko H Zwinderman; Phil Barnett; Tamara T Koopmann; Michiel E Adriaens; Andras Varro; Alfred L George; Christobal dos Remedios; Nanette H Bishopric; Connie R Bezzina; John O'Sullivan; Marc Gewillig; Frances A Bu'Lock; David Winlaw; Shoumo Bhattacharya; Koen Devriendt; JD Brook; Barbara J Mulder; Seema Mital; Alex V Postma; GM Lathrop; Martin Farrall; Judith A Goodship; Bernard D Keavney

doi:10.1038/ng.2637

Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. 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 Moorman
, Aelko H Zwinderman
, Phil Barnett

Tamara T Koopmann, Michiel E Adriaens, Andras Varro, Alfred L George, Christobal dos Remedios, Nanette H Bishopric, Connie R Bezzina, John O'Sullivan, Marc Gewillig, Frances A Bu'Lock, David Winlaw, Shoumo Bhattacharya, Koen Devriendt, JD Brook, Barbara J Mulder, Seema Mital, Alex V Postma, GM Lathrop, Martin Farrall, Judith A Goodship, Bernard D Keavney^*

^*Corresponding author for this work

MaCSBio | Faculty of Science and Engineering

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	822-824
Number of pages	3
Journal	Nature Genetics
Volume	45
Issue number	7
DOIs	https://doi.org/10.1038/ng.2637
Publication status	Published - 2013

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Cordell, H. J., 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, T. J., Hall, D., van Engelen, K., Moorman, A. F., Zwinderman, A. H., ... Keavney, B. D. (2013). Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Nature Genetics, 45(7), 822-824. https://doi.org/10.1038/ng.2637

Cordell, Heather J ; Bentham, Jamie ; Topf, Ana et al. / Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. 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.

@article{c89bdd85bac240bc9d66c760ffda9aa4,

title = "Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.: 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 {\texttimes} 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 {\texttimes} 10⁻⁵; odds ratio (OR) in replication cohort = 1.40, 95\% confidence interval (CI) = 1.19-1.65; combined P = 2.6 {\texttimes} 10⁻¹⁰). Genotype accounted for \textasciitilde{}9\% of the population-attributable risk of ASD.",

author = "Cordell, \{Heather J\} and Jamie Bentham and Ana Topf and Diana Zelenika and Simon Heath and Chrysovalanto Mamasoula and Catherine Cosgrove and Gillian Blue and Javier Granados-Riveron and Kerry Setchfield and Chris Thornborough and Jeroen Breckpot and Rachel Soemedi and Ruairidh Martin and Rahman, \{Thahira J\} and Darroch Hall and \{van Engelen\}, Klaartje and Moorman, \{Antoon F\} and Zwinderman, \{Aelko H\} and Phil Barnett and Koopmann, \{Tamara T\} and Adriaens, \{Michiel E\} and Andras Varro and George, \{Alfred L\} and \{dos Remedios\}, Christobal and Bishopric, \{Nanette H\} and Bezzina, \{Connie R\} and John O'Sullivan and Marc Gewillig and Bu'Lock, \{Frances A\} and David Winlaw and Shoumo Bhattacharya and Koen Devriendt and JD Brook and Mulder, \{Barbara J\} and Seema Mital and Postma, \{Alex V\} and GM Lathrop and Martin Farrall and Goodship, \{Judith A\} and Keavney, \{Bernard D\}",

note = "10.1038/ng.2637",

year = "2013",

doi = "10.1038/ng.2637",

language = "English",

volume = "45",

pages = "822--824",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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}

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, AF, Zwinderman, AH, Barnett, P, Koopmann, TT, Adriaens, ME, Varro, A, George, AL, dos Remedios, C, Bishopric, NH, Bezzina, CR, O'Sullivan, J, Gewillig, M, Bu'Lock, FA, Winlaw, D, Bhattacharya, S, Devriendt, K, Brook, JD, Mulder, BJ, 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. 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

Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. 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 et al.
In: Nature Genetics, Vol. 45, No. 7, 2013, p. 822-824.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.

T2 - Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.

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

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 H

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, JD

AU - Mulder, Barbara J

AU - Mital, Seema

AU - Postma, Alex V

AU - Lathrop, GM

AU - Farrall, Martin

AU - Goodship, Judith A

AU - Keavney, Bernard D

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N2 - 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.

AB - 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.

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SN - 1061-4036

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JO - Nature Genetics

JF - Nature Genetics

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ER -

Cordell HJ, Bentham J, Topf A, Zelenika D, Heath S, Mamasoula C et al. Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Nature Genetics. 2013;45(7):822-824. doi: 10.1038/ng.2637