P3-265: Testing for Association Between Alzheimer's Disease with Psychosis and Variants Identified As Influencing Risk of Schizophrenia

As Alzheimer's disease (AD) progresses many sufferers experience additional behavioural and psychological symptoms such as psychosis. Psychotic symptoms are reported to affect 30–60% of individuals with AD and are associated with more rapid cognitive and functional decline, more severe cognitive impairment, premature institutionalization, and increased risk for agitated and aggressive behaviour. AD with psychosis (AD+P) shows significant familiality and evidence of linkage to specific chromosomal regions, one of which shows overlap with a region previously implicated in schizophrenia and bipolar affective disorder. We have previously shown association of an individual gene with both schizophrenia and the psychosis subtype of AD and consequently hypothesised that variants identified from a genome wide association (GWA) study of schizophrenia (O'Donovan et al., unpublished data) may influence risk for psychotic symptoms in AD. Our schizophrenia GWA study genotyped 479 cases with the Affymetrix GeneChip® 500K Mapping Array in concert with the Wellcome Trust Case Control Consortium study (WTCCC), allowing us to compare allele frequencies with 2937 controls from that study. We chose the twenty-one most positively associated markers from our schizophrenia GWA study and individually genotyped them in a sample of 1205 Caucasian cases of late onset AD (NINCDS-ADRDA criteria) and 1361 aged matched controls from the UK, using the MassARRAY and iPlex systems (Sequenom, San Diego, CA). Preliminary results indicate two nominally significant associations. One marker shows a significant association with psychosis in AD (P = 0.014), while another polymorphism is significantly associated with AD alone (P = 0.019). Full data will be presented. Initial analysis of variants identified from our GWA study of schizophrenia show some evidence of association in both AD+P and AD. These results could support the existence of common aetiological factors influencing common psychotic symptoms on the background of multiple disorders. Alternatively, our results could indicate a complex relationship of psychosis aetiology across diseases, highlighting factors which may show stronger effect in a more severe/homogenous form of AD.