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ARUK 2023 | Epigenome-wide association study of psychosis in Alzheimer’s disease

Morteza Kouhsar, PhD, University of Exeter, Exeter, UK, discusses his work looking into the epigenetic changes associated with psychosis in Alzheimer’s disease (AD). Psychotic symptoms are relatively common in patients with AD, reported to occur in up to 50% of patients, and are associated with a more severe phenotype. Neurobiological data are emerging that link late-life psychosis to neurodegeneration and a recent international genome-wide association study (GWAS) reported the first genome-wide significant risk loci for psychosis in AD. Despite ongoing developments, much remains unknown about the mechanisms underlying psychosis in AD. Hoping to understand more about the mechanisms at play, Dr Kouhsar performed an epigenome-wide association study (EWAS) of thousands of CpG methylation sites to identify differences in methylation in patients with AD with and without psychosis. The study identified several notable sites that were differentially methylated. After identifying significant methylation quantitative trait loci, the results were compared with GWAS results for other related traits, including anxiety and schizophrenia, which highlighted putatively causal SNPs that were shared between traits. Further study of these methylation quantitative trait loci and their links with disease-associated variants may shed light on the mechanisms underlying psychosis in AD. This interview took place at the Alzheimer’s Research UK (ARUK) Conference 2023 in Aberdeen, UK.

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