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Design and rationale of a genetic cohort study on congenital cardiac disease: experiences from a multi-institutional platform in Quebec

Published online by Cambridge University Press:  04 July 2011

Marie-Pierre Dubé ,
Jean-Luc Bigras ,
Maryse Thibeault ,
Nathalie Bureau ,
Philippe Chetaille ,
Andrea Richter ,
Jocelyne Mercier ,
Marc Bellavance ,
Charles Rohlicek  and
Rima Rozen
...Show all authors
Marie-Pierre Dubé
Affiliation:
Montreal Heart Institute, University of Montreal, 5000, Rue Belanger, Canada
Jean-Luc Bigras
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
Maryse Thibeault
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
Nathalie Bureau
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
Philippe Chetaille
Affiliation:
Cardiology Service, Centre Mère-Enfants, Centre Hospitalier Universitaire de Québec, 2705, boulevard Laurier, Québec, Canada
Andrea Richter
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
Jocelyne Mercier
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
Marc Bellavance
Affiliation:
Department of Pediatrics, University of Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada
Charles Rohlicek
Affiliation:
Department of Pediatrics, McGill University, Montréal, 3400, boulevard De Maisonneuve Ouest, Montreal, QC, Canada
Rima Rozen
Affiliation:
Department of Pediatrics, McGill University, Montréal, 3400, boulevard De Maisonneuve Ouest, Montreal, QC, Canada
Mona Nemer
Affiliation:
University of Ottawa, 550, rue Cumberland, Ottawa, ON, Canada
Paul Khairy
Affiliation:
Montreal Heart Institute, University of Montreal, 5000, Rue Belanger, Canada
Roxanne Gendron
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
Gregor Andelfinger*
Affiliation:
Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, University of Montreal, 3175 Chemin Côte Sainte Catherine, Montréal, Canada
*
Correspondence to: Dr G. Andelfinger, MD, Research Center, Room 2724, CHU Sainte Justine, 3175, Côte Sainte Catherine, Montréal, Québec H3T 1C5, Canada. Tel: 514 345 4931x3244; Fax: 514 345 4896; E-mail: [email protected]
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Abstract

Background

Congenital cardiac disease is the most common malformation, and a substantial source of mortality and morbidity in children and young adults. A role for genetic factors is recognised for these malformations, but overall few predisposing loci have been identified. Here we report the rationale, design, and first results of a multi-institutional congenital cardiac disease cohort, assembled mainly from the French-Canadian population of the province of Quebec and centred on families with multiple affected members afflicted by cardiac malformations.

Methods

Families were recruited into the study, phenotyped and sampled for DNA in cardiology clinics over the first 3 years of enrolment. We performed segregation analysis and linkage simulations in the subgroup of families with left ventricular outflow tract obstruction (LVOTO).

Results

A total of 1603 participants from 300 families were recruited, with 169 out of 300 (56.3%) families having more than one affected member. For the LVOTO group, we estimate heritability to be 0.46–0.52 in our cohort. Simulation analysis demonstrated sufficient power to carry out linkage analyses, with an expected mean log-of-odds (LOD) score of 3.8 in 67 pedigrees with LVOTO.

Conclusion

We show feasibility and usefulness of a population-based biobank for genetic investigations into the causes of congenital cardiac disease. Heritability of LVOTO is high and could be accounted for by multiple loci. This platform is ideally suited for multiple analysis approaches, including linkage analysis and novel gene sequencing approaches, and will allow to establish segregation of risk alleles at family and population levels.

Keywords

Cardiac malformationspopulation studybiobankingheritability analysispower simulations
Type
Original Articles
Information
Cardiology in the Young , Volume 21 , Issue 6 , 28 October 2011 , pp. 654 - 664
Copyright
Copyright © Cambridge University Press 2011

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