A canine chromosome 7 locus confers compulsive disorder susceptibility

Dodman, Nicholas H.; Karlsson, Elinor K.; Moon-Fanelli, Alice A.; Galdzicka, Marzena; Perloski, Michele; Shuster, Louis; Lindblad‐Toh, Kerstin; Ginns, Edward I.

doi:10.1038/mp.2009.111

Cited by 117 publications

(109 citation statements)

References 10 publications

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“…[56][57][58] Of related interest, variants in CDH2 and other cadherins have been widely found to CDH2 variants in OCD and TD PR Moya et al be associated with various cancers 16,59,60 and, specifically, upregulated CDH2 has been associated with transepithelial spreading of melanoma and pancreatic cancer together with rapid recurrence of cancer. [61][62][63] In summary, although CDH2 is an attractive candidate gene based on the CCD study findings, 11 the present results suggest that these CDH2 variants are not disease-causing by themselves. Further studies are needed to clarify if N706S and N845S, identified in OCD and TD subgroups, may or may not be risk factors of interest in OCD/TD when investigated in larger cohorts.…”

Section: Resultsmentioning

confidence: 70%

“…[7][8][9][10] Recently, single-nucleotide polymorphisms (SNPs) within the canine neuronal cadherin gene (CDH2) were shown to confer a significant risk for canine compulsive disorder (CCD). 11 CCD shares many similarities with OCD: (a) both are characterized by repetitive, timeconsuming behaviors that cause distress and functional impairment; (b) both have at least partially genetic heritabilities; and (c) symptoms in both humans and dogs can be alleviated by behavioral therapy, administration of antidepressants or a combination of both therapies. 12,13 CDH2 belongs to the cadherin gene family of cell-cell adhesion molecules, which function in early brain morphogenesis, synaptogenesis and synaptic plasticity, including synaptic vesicle trafficking in glutamatergic neurons.…”

Section: Introductionmentioning

confidence: 99%

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Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

et al. 2013

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The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N ¼ 1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P ¼ 0.014, OR ¼ 6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders.

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Section: Resultsmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

et al. 2013

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“…A study on dogs displaying compulsive sucking behaviour demonstrated an association with the CDH2 locus (Dodman et al, 2010). Luesher et al (1998) suggested that crib-biting could represent an equine compulsion.…”

Section: Discussionmentioning

confidence: 99%

“…Opioid receptor supersensitivity has been demonstrated to be associated with stereotypy in rats (Broderick et al, 1983) and endogenous opioids are involved in the stereotyped behaviour of tethered sows (Cronin et al, 1985). Association with the CDH2 region was found in a canine compulsive disorder (Dodman et al, 2010). Semaphorin genes have been implicated in psychiatric disorders in humans (Mann et al, 2007) and Sema6A-deficient mice revealed a hyperactive phenotype (Rünker et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Pedigree studies also suggest the involvement of genetic factors, although the mode of inheritance has not been determined (Vecchiotti and Galanti, 1986). Genetic evidence in other animal stereotypies has been established, including examples such as bank voles (Schoenecker and Heller, 2000) and compulsive dogs (Dodman et al, 2010). Stress, gastric discomfort and frustration caused by stall restrictions and early weaning (Nicol et al, 2002;Latham and Mason, 2008;Hothersall and Nicol, 2009) have been suggested as additional risk factors for equine crib-biting.…”

Section: Introductionmentioning

confidence: 99%

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Exploration of known stereotypic behaviour-related candidate genes in equine crib-biting

Hemmann

Ahonen

Raekallio

et al. 2014

Animal

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Crib-biting in horses is a stereotypic oral behaviour. Genetic susceptibility has been suggested on a causal basis, together with environmental factors such as stress, gastric discomfort and frustration caused by stall restrictions. This study aimed to test the associations of known or suspected stereotypic genes with equine crib-biting, including Ghrelin, Ghrelin receptor, Leptin, Dopamine receptor, μ-opioid receptor, N-cadherin, Serotonin receptor and Semaphorin. We conducted a candidate gene study with a case-control design, including 98 crib-biting and 135 control horses of two breeds, Finnhorses and half-breds. Detailed phenotypic information on crib-biting behaviour was surveyed through an owner-completed questionnaire. Control horses were more than 10 years old and without a history of crib-biting. Single nucleotide polymorphisms flanking the candidate genes were genotyped using either Sanger sequencing or Taqman assays. According to the survey, the affected horses started crib-biting at a young age, had exhibited crib-biting for more than a year, and expressed the behaviour after feeding or when stressed. Comparison of allele frequencies between the cases and controls for each breed separately did not provide evidence of an association at any of the tested loci. These results suggest that the previously known stereotypic genes are not major risk factors for crib-biting in horses, and further genome-wide studies are warranted on larger sample cohorts.

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Behavioral Pharmacotherapy in the Animal Shelter

Marder

2012

Shelter Medicine for Veterinarians and Staff

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A canine chromosome 7 locus confers compulsive disorder susceptibility

Cited by 117 publications

References 10 publications

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

Exploration of known stereotypic behaviour-related candidate genes in equine crib-biting

Behavioral Pharmacotherapy in the Animal Shelter

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