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297 Genetic associations of ICD in parkinson’s disease
  1. Rees Richard1,
  2. Hubbard Leon2,
  3. Ben-Shlomo Yoav3,
  4. Grosset Donald4,
  5. Williams Nigel2,
  6. Morris Huw1
  1. 1Department of Clinical Neuroscience, UCL Institute of Neurology
  2. 2Division of Psychological Medicine and Clinical Neurosciences, University of Cardiff
  3. 3Population Health Sciences, Bristol Medical School
  4. 4Institute of Neurological Sciences, Queen Elizabeth University Hospital

Abstract

Introduction Impuse Control Disorders (ICD) are a potentially devastating side-effect of dopaminergic therapy in Parkinson’s disease (PD). We explore the genetic factors associated with ICD in Tracking Parkinson’s/PRoBaND – a UK-wide cohort of early-stage PD.

Methods Participants were diagnosed with PD within 3 years and had longitudinal assessment including the Questionnaire for ICD in Parkinson’s (QUIP) for up to 5 years. We defined cases as having any positive response to the QUIP (lax criteria) or 2 positive responses in any domain (strict criteria). We performed a candidate-gene analysis based on systematic review, followed by a genome-wide association study. We used age at onset, gender, and three significant principle components as covariates.

Results After clinical and genetic quality control steps, we analysed 1602 participants. Prevalence was significantly affected by classification criteria (strict/lax): ICD – 26.8%/11.1%, IRB 29.3%/27.2%, any 31.7%/41.9%. Six SNPs in dopamine, glutamate and adreno- receptor genes achieved nominal significance (p<0.05) in the candidate study. We have identified several SNPs in the GWAS that approach genome wide significance (p<5 × 10–7).

Conclusions This work is the first genome-wide study of genetic determinants of ICD. Our findings support the hypothesis of genetic determinants of ICD in Parkinson’s and further work will allow understanding of the biology of ICD.

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