A novel locus in chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers

Presenter Julia Niskanen
Authors Julia Niskanen (1,2,3), Marjo K Hytönen (1,2,3), Tosso Leeb (4), Frank van Steenbeek (5), Maria Wiberg (6), Gerhard Wess (7) Hannes Lohi (1,2,3)
Affiliations 1. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland; 2. Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland; 3. The Folkhälsan Institute of Genetics, Helsinki, Finland; 4. Institute of Genetics, University of Bern, Bern, Switzerland; 5. Utrecht University, Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht, The Netherlands; 6. Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; 7. Medizinische Kleintierklinik, Ludwig Maximilian University of Munich, Munich, Germany
Presentation Type Talk


Dilated cardiomyopathy (DCM) is a breed-specific, high prevalence disorder in Doberman Pinschers. However, the genetic background of DCM and its relationship to cardiac arrhythmias remains largely unknown. To uncover the genetic risk loci and variants that are associated with DCM, we have established a cohort of over 550 Dobermans with cardiological examination, which included echography, electrocardiogram and 24-hour Holter monitoring. The cohort was genotyped using Affymetrix Axiom 2.0 arrays with ~1.2 M SNPs, and 180 cases and 180 controls that met inclusion criteria were selected for analysis. About 290k informative SNPs remained for analysis after quality control. Genome wide association analysis was performed with single-locus and mixed model approaches and multiple testing was corrected by permutation or Bonferroni correction. A novel locus in chromosome 5 was revealed with genome wide significance (praw=1.376×10-11, pBonf=4.099×10-6). This new locus is different from the previously published locus in chromosome 5. The ~1.4 Mb critical region covered by the 15 SNPs passing genome wide significance contains several genes potentially relevant for cardiac function and for DCM specifically. Ongoing whole genome sequencing analyses aim to discover the causative variant in the associated region. This study demonstrates the power of the new high-density SNP array and is expected to provide a novel DCM candidate gene, new insights to disease mechanism and tools for breeding purposes.