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Publication Detail
No evidence for excess runs of homozygosity in bipolar disorder
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Vine AE, McQuillin A, Bass NJ, Pereira A, Kandaswamy R, Robinson M, Lawrence J, Anjorin A, Sklar P, Gurling HM, Curtis D
  • Publication date:
    2009
  • Pagination:
    165, 170
  • Journal:
    Psychiatr Genet
  • Volume:
    19
  • Medium:
    4
  • Print ISSN:
    1473-5873
  • Keywords:
    Bipolar Disorder/*genetics Case-Control Studies Haplotypes Heterozygote *Homozygote Humans
  • Notes:
    Vine, Anna E McQuillin, Andrew Bass, Nicholas J Pereira, Ana Kandaswamy, Radhika Robinson, Michele Lawrence, Jacob Anjorin, Adebayo Sklar, Pamela Gurling, Hugh M D Curtis, David eng 076392/Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't England 2009/05/20 09:00 Psychiatr Genet. 2009 Aug;19(4):165-70. doi: 10.1097/YPG.0b013e32832a4faa. BACKGROUND: Recent studies have reported large common regions of homozygosity (ROHs) that are the result of autozygosity, that is, the cooccurrence within individuals of long haplotypes that have a high frequency in the population. A recent study reports that such regions are found more commonly in individuals with schizophrenia compared with controls, and identified nine 'risk ROHs' that were individually more common in cases. Of these, four contained or neighboured genes associated with schizophrenia (NOS1AP/UHMK1, ATF2, NSF and PIK3C3). METHODS: We have applied the same methodology to a UK sample of 506 cases with bipolar disorder and 510 controls. RESULTS: There was no overall excess of common ROHs among bipolar individuals. With one exception, the haplotypes accounting for the ROHs appeared to be distributed according to the Hardy-Weinberg equilibrium. One ROH was individually more common among cases (uncorrected P = 0.0003). This ROH spanned the chromosome 2p23.3 gene ITSN2 (the gene for intersectin 2 isoform 2). However, inspection of the homozygous haplotypes and haplotype-based tests for association failed to provide a clearer understanding of why this ROH was occurring more commonly. CONCLUSION: Overall, we conclude that, in contrast with schizophrenia, common ROHs are rarely associated with susceptibility to bipolar disorder. This supports the idea that predominantly different genes are increasing susceptibility to schizophrenia and bipolar affective disorders.
Abstract
BACKGROUND: Recent studies have reported large common regions of homozygosity (ROHs) that are the result of autozygosity, that is, the cooccurrence within individuals of long haplotypes that have a high frequency in the population. A recent study reports that such regions are found more commonly in individuals with schizophrenia compared with controls, and identified nine 'risk ROHs' that were individually more common in cases. Of these, four contained or neighboured genes associated with schizophrenia (NOS1AP/UHMK1, ATF2, NSF and PIK3C3). METHODS: We have applied the same methodology to a UK sample of 506 cases with bipolar disorder and 510 controls. RESULTS: There was no overall excess of common ROHs among bipolar individuals. With one exception, the haplotypes accounting for the ROHs appeared to be distributed according to the Hardy-Weinberg equilibrium. One ROH was individually more common among cases (uncorrected P = 0.0003). This ROH spanned the chromosome 2p23.3 gene ITSN2 (the gene for intersectin 2 isoform 2). However, inspection of the homozygous haplotypes and haplotype-based tests for association failed to provide a clearer understanding of why this ROH was occurring more commonly. CONCLUSION: Overall, we conclude that, in contrast with schizophrenia, common ROHs are rarely associated with susceptibility to bipolar disorder. This supports the idea that predominantly different genes are increasing susceptibility to schizophrenia and bipolar affective disorders.
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