Replication of GWAS of bipolar disorder: association of SNPs near CDH7 with bipolar disorder and visual processing

Soronen, Pia; Ollila, Hanna; Antila, M.; Silander, Kaisa; Palo, Outi M.; Kieseppä, Tuula; Lönnqvist, Jouko; Peltonen, Leena; Tuulio-Henriksson, A; Partonen, Timo; Paunio, Tiina

doi:10.1038/mp.2009.86

Cited by 26 publications

(16 citation statements)

References 11 publications

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“…[18][19][20]44,45 Protocadherins and other cadherins have also been studied as candidate risk genes, but generally in small samples (o100 patients) of schizophrenia, bipolar disorder and OCD patients. [46][47][48][49][50][51][52][53][54][55] In addition, some cadherins have been specifically identified in genome-wide association scans of ADHD, addiction and neuroticism personality features. [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.…”

Section: Resultsmentioning

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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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: 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 recent GWAS study in bipolar disorder and subsequent replication efforts have provided some support for association with CDH7. 24 A GWAS study in ASDs identified association with the chromosome 5p14.1 region containing other members of the cadherin superfamily, CDH 9 and CDH 10. 25 Wang and colleagues went further and in a strategy not dissimilar to our approach applied two pathway-based association analyses to their genotype data.…”

Section: Neuronal Cell Adhesion Genesmentioning

confidence: 99%

Neuronal cell adhesion genes

Corvin

2010

Cell Adhesion & Migration

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“…A synthetic peptide derived from the neuronal CAM has been found to influence memory consolidation in an animal model at both behavioural and hippocampal neuron phenotypes (Cambon et al 2004). In patients, Soronen et al (2010) found that the gene CDH7 is associated with variation in performance on measures of working memory and visual attention in patients with bipolar disorder. Contactin-associated protein-like-2 (CNTNAP2), which encodes a member of the neurexin family, has been implicated in SZ and associated with epilepsy and intellectual disability (Friedman et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…cadherin-4, CDH4; Wang et al 2009), cell-cell binding (e.g. cadherin-7, CDH7;Soronen et al 2010) and synapse formation (e.g. neurexin; Dean et al 2003).…”

Section: Introductionmentioning

confidence: 99%

The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis

et al. 2013

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Background. Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.Method. In total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.Results. Increased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1-3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.Conclusions. These data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.

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Replication of GWAS of bipolar disorder: association of SNPs near CDH7 with bipolar disorder and visual processing

Cited by 26 publications

References 11 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

Neuronal cell adhesion genes

The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis

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