title: Design and rationale of a genetic cohort study on congenital cardiac disease: experiences from a multi-institutional platform in Quebec.
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.
  
  
  CONCLUSIONS
  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.
authors: Montreal Heart Institute, University of Montreal, Rue Belanger, Canada.
authors: Marie-Pierre
authors: MP
authors: Dubé
authors: Jean-Luc
authors: JL
authors: Bigras
authors: Maryse
authors: M
authors: Thibeault
authors: Nathalie
authors: N
authors: Bureau
authors: Philippe
authors: P
authors: Chetaille
authors: Andrea
authors: A
authors: Richter
authors: Jocelyne
authors: J
authors: Mercier
authors: Marc
authors: M
authors: Bellavance
authors: Charles
authors: C
authors: Rohlicek
authors: Rima
authors: R
authors: Rozen
authors: Mona
authors: M
authors: Nemer
authors: Paul
authors: P
authors: Khairy
authors: Roxanne
authors: R
authors: Gendron
authors: Gregor
authors: G
authors: Andelfinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006343:Heart Septal Defects / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011792:Quebec; D012107:Research Design; D013771:Tetralogy of Fallot / Q000235:genetics; D014694:Ventricular Outflow Obstruction / Q000235:genetics; D055815:Young Adult