RGD Reference Report - DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder. - Rat Genome Database

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DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.

Authors: Hennah, W  Thomson, P  McQuillin, A  Bass, N  Loukola, A  Anjorin, A  Blackwood, D  Curtis, D  Deary, IJ  Harris, SE  Isometsa, ET  Lawrence, J  Lonnqvist, J  Muir, W  Palotie, A  Partonen, T  Paunio, T  Pylkko, E  Robinson, M  Soronen, P  Suominen, K  Suvisaari, J  Thirumalai, S  St Clair, D  Gurling, H  Peltonen, L  Porteous, D 
Citation: Hennah W, etal., Mol Psychiatry. 2009 Sep;14(9):865-73. Epub 2008 Mar 4.
RGD ID: 5509836
Pubmed: PMID:18317464   (View Abstract at PubMed)
DOI: DOI:10.1038/mp.2008.22   (Journal Full-text)

Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020; corrected P=0.016; odds ratio=2.73+/-95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds ratio=1.64+/-95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio=1.27+/-95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Asperger syndrome susceptibilityIAGP 5509836DNA:SNPs: :RGD 
Asperger syndrome susceptibilityISODISC1 (Homo sapiens)5509836; 5509836DNA:SNPs: :RGD 
autistic disorder susceptibilityIAGP 5509836DNA:polymorphism:microsatellite:RGD 
autistic disorder susceptibilityISODISC1 (Homo sapiens)5509836; 5509836DNA:polymorphism:microsatellite:RGD 
bipolar disorder  IAGP 5509836DNA:SNPs: :rs1538979 more ...RGD 
bipolar disorder  ISODISC1 (Homo sapiens)5509836; 5509836DNA:SNPs: :rs1538979 more ...RGD 
schizophrenia  IAGP 5509836DNA:SNPs: :rs1538979 more ...RGD 
schizophrenia  ISODISC1 (Homo sapiens)5509836; 5509836DNA:SNPs: :rs1538979 more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Disc1  (DISC1 scaffold protein)

Genes (Mus musculus)
Disc1  (disrupted in schizophrenia 1)

Genes (Homo sapiens)
DISC1  (DISC1 scaffold protein)


Additional Information