title: Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci.
abstract: BACKGROUND
  Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects - for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD.
  
  
  RESULTS
  We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, P(empirical) = 0.0004) and at chromosome 18 (18q21.2, P(empirical) = 0.0005).
  
  
  CONCLUSIONS
  In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD.
authors.affiliation: Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany. antonia.flaquer@lmu.de
authors.forename: Antònia
authors.initials: A
authors.lastname: Flaquer
authors.forename: Clemens
authors.initials: C
authors.lastname: Baumbach
authors.forename: Estefania
authors.initials: E
authors.lastname: Piñero
authors.forename: Fernando
authors.initials: F
authors.lastname: García Algas
authors.forename: María Angeles
authors.initials: MA
authors.lastname: de la Fuente Sanchez
authors.forename: Jordi
authors.initials: J
authors.lastname: Rosell
authors.forename: Jorge
authors.initials: J
authors.lastname: Toquero
authors.forename: Luis
authors.initials: L
authors.lastname: Alonso-Pulpon
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Pavia
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Damian
authors.initials: D
authors.lastname: Heine-Suñer
mesh_terms: D002884:Chromosomes, Human, Pair 15; D002887:Chromosomes, Human, Pair 18; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans