Open Access Research article

Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci

Antònia Flaquer12*, Clemens Baumbach12, Estefania Piñero3, Fernando García Algas4, María Angeles de la Fuente Sanchez4, Jordi Rosell5, Jorge Toquero6, Luis Alonso-Pulpon6, Pablo Garcia-Pavia6, Konstantin Strauch12 and Damian Heine-Suñer5

Author Affiliations

1 Institute of Medical Informatics, Biometry, and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany

2 Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

3 Research Unit, Son Espases University Hospital, Palma de Mallorca, Spain

4 Pediatric Cardiology, Son Espases University Hospital, Palma de Mallorca, Spain

5 Genetic Section, Son Espases University Hospital, Palma de Mallorca, Spain

6 Cardiomyopathy Unit, Department of Cardiology, Puerta de Hierro University Hospital, Madrid, Spain

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BMC Genetics 2013, 14:44  doi:10.1186/1471-2156-14-44

Published: 24 May 2013



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.


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, Pempirical = 0.0004) and at chromosome 18 (18q21.2, Pempirical = 0.0005).


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.

Congenital heart defects; Genetics; Linkage analysis; Genome-wide study