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.
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.
Authors: Elizabeth A Heron; Paul Cormican; Gary Donohoe; Francis A O'Neill; Kenneth S Kendler; Brien P Riley; Michael Gill; Aiden P Corvin; Derek W Morris Journal: Schizophr Res Date: 2014-02-20 Impact factor: 4.939
Authors: Francisco C Ceballos; Peter K Joshi; David W Clark; Michèle Ramsay; James F Wilson Journal: Nat Rev Genet Date: 2018-01-15 Impact factor: 53.242
Authors: Paraskevi Christofidou; Christopher P Nelson; Majid Nikpay; Liming Qu; Mingyao Li; Christina Loley; Radoslaw Debiec; Peter S Braund; Matthew Denniff; Fadi J Charchar; Ares Rocanin Arjo; David-Alexandre Trégouët; Alison H Goodall; Francois Cambien; Willem H Ouwehand; Robert Roberts; Heribert Schunkert; Christian Hengstenberg; Muredach P Reilly; Jeanette Erdmann; Ruth McPherson; Inke R König; John R Thompson; Nilesh J Samani; Maciej Tomaszewski Journal: Am J Hum Genet Date: 2015-07-09 Impact factor: 11.025
Authors: Mirte Bosse; Hendrik-Jan Megens; Ole Madsen; Yogesh Paudel; Laurent A F Frantz; Lawrence B Schook; Richard P M A Crooijmans; Martien A M Groenen Journal: PLoS Genet Date: 2012-11-29 Impact factor: 5.917