Evidence that variation in the oligodendrocyte lineage transcription factor 2 ( OLIG2) gene is associated with psychosis in Alzheimer's disease

Abstract

Psychotic symptoms are common in individuals with Alzheimer's disease (AD), and define a phenotype associated with more rapid cognitive and functional decline. Evidence suggests that psychotic symptoms may be influenced by genetic factors, and recent studies in schizophrenia, bipolar affective disorder (BPAD) and Alzheimer's disease with psychosis (AD + P) suggest that psychosis susceptibility or modifier genes may act across diseases. We hypothesised that oligodendrocyte lineage transcription factor 2 ( OLIG2), a regulator of white matter development and a candidate gene for schizophrenia, may also be associated with psychotic symptoms in AD. We genotyped 11 SNPs in OLIG2 previously tested for association with schizophrenia [L. Georgieva, V. Moskvina, T. Peirce, N. Norton, N.J. Bray, L. Jones, P. Holmans, S. Macgregor, S. Zammit, J. Wilkinson, H. Williams, I. Nikolov, N. Williams, D. Ivanov, K.L. Davis, V. Haroutunian, J.D. Buxbaum, N. Craddock, G. Kirov, M.J. Owen, M.C. O’Donovan, Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia, Proc. Natl. Acad. Sci. U.S.A. 103 (33) (2006) 12469–12474] and tested these for association with AD and AD + P. Significant evidence for association of psychotic symptoms within cases was identified for two SNPs, rs762237 (allelic P = 0.002, OR = 1.42, corrected P = 0.019) and rs2834072 (allelic P = 0.004, OR = 1.41, corrected P = 0.05).