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A canine chromosome 7 locus confers compulsive disorder susceptibility

Molecular Psychiatry volume 15, pages 8–10 (2010)Cite this article

Human and canine compulsive disorders (CCDs) manifest as time-consuming, repetitive behaviors causing distress and functional impairment. CCDs derive from normal behaviors such as grooming (acral lick dermatitis), predatory behavior (tail chasing, fly snapping), eating/suckling (pica and flank sucking (FS)/blanket sucking (BS)) or locomotion (pacing/circling). They commonly appear between pre-pubescence and early social maturity1 and may be precipitated by anxiety or stress. However, the behavior soon becomes ‘fixed’ and is shown even in the absence of obvious stressors. CCD has compelling parallels with human obsessive–compulsive disorder (OCD).2, 3 OCD, characterized by recurring obsessions and/or compulsions, affects millions of individuals.4 Here, we describe the novel association of Doberman pincher CCD with a chromosome 7 locus containing CDH2, an attractive candidate.

Fine-mapping using 84 SNPs across 1.7 Mb surrounding the chromosome 7 peak, including nine SNPs from the genome-wide analysis, was performed on an increased sample number (94 affected; 73 controls). After analyzing 63 SNPs passing quality filters, the association peak remained at 63.867472 Mb (Praw=5.5 × 10−6). Multi-SNP haplotype testing revealed an extended region of moderate association spanning roughly 400 kb (63.8–64.2 Mb), likely reflecting the long haplotypes found within dog breeds. The most significantly associated SNP is located within CDH2 (Figure 1c). CDH2 is widely expressed, mediating synaptic activity-regulated neuronal adhesion.7 Dogs showing multiple compulsive behaviors have a higher frequency of the risk allele than dogs with a less severe phenotype (60 and 43%, respectively, compared with 22% in unaffected dogs; Figure 1d).

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Author notes

  1. E K Karlsson and A Moon-Fanelli: These authors contributed equally to this work.

Authors and Affiliations

  1. Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA

    N H Dodman & A Moon-Fanelli

  2. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    E K Karlsson, M Perloski & K Lindblad-Toh

  3. FAS Center for Systems Biology, Harvard University, Cambridge, MA, USA

    E K Karlsson

  4. University of Massachusetts Medical School, Worcester, MA, USA

    M Galdzicka & E I Ginns

  5. Tufts University School of Medicine, Boston, MA, USA

    L Shuster

  6. Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

    K Lindblad-Toh

Authors
  1. N H Dodman
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  2. E K Karlsson
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  3. A Moon-Fanelli
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  4. M Galdzicka
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  5. M Perloski
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  6. L Shuster
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  7. K Lindblad-Toh
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  8. E I Ginns
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Corresponding author

Correspondence to N H Dodman.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Dodman, N., Karlsson, E., Moon-Fanelli, A. et al. A canine chromosome 7 locus confers compulsive disorder susceptibility. Mol Psychiatry 15, 8–10 (2010). https://doi.org/10.1038/mp.2009.111

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