AbstractBackgroundDementia with Lewy bodies (DLB), Parkinson’s disease (PD) and Parkinson’s disease dementia (PDD) are termed Lewy body diseases (LBDs). These neurodegenerative diseases are classified by the accumulation of alpha‐synuclein in neurons, forming Lewy bodies (LB). Whilst pathologically similar, symptomatic staging is different. Previous genome wide association studies (GWAS) have identified classic Alzheimer’s disease (AD) and PD loci as risk loci in DLB. Therefore, we have used polygenic risk score (PRS) analysis to investigate the contribution of AD and PD variants in the LBDs.MethodDNA was extracted from bulk brain tissue from 481 individuals (162 controls, 95 DLB, 156 PDD and 68 PD) and genotyped on the Illumina global screening array. After a strict quality control and imputation pipeline, PRSs for multiple relevant traits using reference GWAS summary statistics were calculated using PRSice2.ResultStudy groups have been sourced consisting of cases with PD, PDD and DLB based on LB deposition and clinical symptom staging. All groups, including controls are stratified for age and concomitant AD pathology. Assessing multiple PRSs for association with pathological development and clinical outcomes we have identified the contribution of genetic risk from related neurodegenerative and neuropsychiatric disorders in our cohort of PD, PDD and DLB samples.ConclusionWe have collated a well powered study cohort to interrogate the genetic basis of the Lewy body dementias and the relative contribution of AD and PD risk loci in the LBDs. We are currently generating methylation quantitative trait loci (mQTLs) for this dataset using previously generated matched DNA methylation data in the brain.