Principal Investigator: Dr Laurie Ozelius
Massachusetts General HospitalTags: 51811, disease risk, dystonia, GWAS, Parkinson’s disease, rare disease, wes
Dystonia is a neurologic disorder characterized by abnormal body posture and tone. Parkinson’s disease has features of bradykinesia, rigidity, tremor, and postural instability. Together both diseases make up a significant proportion of global morbidity from movement disorders. Although much progress has been made in recent years in identifying the genetic underpinnings of dystonia and Parkinson’s disease, we know that there is more “missing heritability” in these two disorders and that the contribution of genetic risk factors to disease is more than what can currently be explained by known genes.
Our group is interested in discovering genes associated with risk of dystonia and Parkinson’s disease. Using exome sequencing and SNP genotyping arrays, we have obtained genetic information from 1000+ individuals afflicted with these disorders, mostly of European descent. The analysis involves identifying variations that are enriched in the patient cohort in comparison to population reference databases like the UK Biobank. We aim to identify variants in genes that are by themselves causative of dystonia or Parkinson’s disease, or that contribute to the risk of these two diseases. In addition, we aim to resolve outstanding questions on the penetrance of these disorders, using genotype and phenotype information from the UK Biobank (i.e., absence of neurologic disease as reported) and other databases. The analysis is expected to be complete in 2 years and, will involve participants from our dystonia-Parkinson’s disease cohort and neurologically normal participants in the UK Biobank.