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).
We have applied the same methodology to a UK sample of 506 cases with bipolar disorder and 510 controls.
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.
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.
aCentre for Psychiatry, Barts and the London School of Medicine and Dentistry
bMolecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute of Medical Sciences, University College London, London, UK
cCenter for Human Genetic Research
dDepartment of Psychiatry, Massachusetts General Hospital
eDepartments of Genetics, Psychiatry or Medicine, Harvard Medical School, Boston
fBroad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Correspondence to Professor David Curtis, MD, PhD, Barts and the London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, London E1 1BB, UK
Tel: +44 20 7377 7729; e-mail: firstname.lastname@example.org
Received 6 July 2008 Revised 17 November 2008 Accepted 23 November 2008