Chromosome 13q13-q14 locus overlaps mood and psychotic disorders: The relevance for redefining phenotype

Department of Psychiatry, Laval University, Québec, QC, Canada.
European journal of human genetics: EJHG (Impact Factor: 4.35). 02/2009; 17(8):1034-42. DOI: 10.1038/ejhg.2008.268
Source: PubMed


The nosology of major psychoses is challenged by the findings that schizophrenia (SZ) and bipolar disorder (BP) share several neurobiological, neuropsychological and clinical phenotypic characteristics. Moreover, several vulnerability loci or genes may be common to the two DSM disorders. We previously reported, in a sample of 21 kindreds (sample 1), a genome-wide suggestive linkage in 13q13-q14 with a common locus (CL) phenotype that crossed the diagnostic boundaries by combining SZ, BP and schizoaffective disorders. Our objectives were to test phenotype specificity in a separate sample (sample 2) of 27 kindreds from Eastern Quebec and to also analyze the combined sample of 48 kindreds (1274 family members). We performed nonparametric and parametric analyses and tested as phenotypes: SZ alone, BP alone, and a CL phenotype. We replicated in sample 2 our initial finding with CL with a maximum NPL(pair) score of 3.36 at D13S1272 (44 Mb), only 2.1 Mb telomeric to our previous maximum result. In the combined sample, the peak with CL was at marker D13S1297 (42.1 Mb) with a NPL(pair) score reaching 5.21, exceeding that obtained in each sample and indicating consistency across the two samples. Our data suggest a susceptibility locus in 13q13-q14 that is shared by schizophrenia and mood disorder. That locus would be additional to another well documented and more distal 13q locus where the G72/G30 gene is mapped.

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    • "The adult members affected by schizophrenia or bipolar disorders came from the same large densely affected multigenerational kindreds (Maziade et al., 2009a, 2005; Mérette et al., 2008). We have already shown that these patients with schizophrenia and bipolar disorders shared similar cognitive deficits (Maziade et al., 2009b). "
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    ABSTRACT: The developmental aspects of cognitive structures from childhood until adulthood and across different levels of risk for psychopathology have been little studied. The aim of the current study was to explore the cognitive factorial structure in subsamples from highly familial and densely affected kindreds of schizophrenia and bipolar disorder - i.e. affected adult members, non-affected adult members and high-risk youth. The same neuropsychological battery was administered in a sample of 480 participants: schizophrenia and bipolar patients (n=51), young high-risk offspring (n=61), non-affected adult relatives of patients (n=96), and controls (n=272). Exploratory Factorial Analysis was performed in the control sample and yielded a 5-factor solution: verbal comprehension, processing speed/working memory, visual learning and memory, verbal learning and memory, reasoning and problem solving. Confirmatory factor analysis indicated that the hierarchical 5-factor solution was well suited for the young high-risk offspring, the non-affected adult relatives of patient and the patients. A hierarchical model with a "g" factor was a good fit for all subsamples. These results suggest that cognitive impairments may aggregate in highly familial individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research 07/2015; 229(1-2):101-8. DOI:10.1016/j.psychres.2015.07.063 · 2.47 Impact Factor
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    • "Goes et al. [34] showed evidence for familial aggregation to mood incongruent psychotic symptoms among patients with bipolar disorder for 13q32 region. Other studies have reported association with the nearby 13q13–14 region (i.e., [17]). However, recent large schizophrenia GWAS analyses have failed to report significant association in both regions [35] and there are no obvious known variants that explain the observed linkage signal [10]. "
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    PLoS ONE 12/2012; 7(12):e52262. DOI:10.1371/journal.pone.0052262 · 3.23 Impact Factor
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    • "A linkage scan has identified chromosome 13 of interest for alcohol and illicit drug dependence but this region does not overlap KPNA3 [2]. Other studies show that chromosome 13q14 is a susceptibility locus for mood disorder and bipolar disorder [19] [23]. "
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    ABSTRACT: KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.
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