Objective: The program aim is to assess the contribution of genes and environment influencing susceptibility, progression and the relative contribution of risk factors underlying Parkinson’s disease (PD) utilizing a combined population and pedigree approach.

Background: The etiology of PD is unknown. Large-scale genetic association studies have revealed clues to causation, but environmental risk factors through gene-environment interactions have also been suggested to be involved in disease etiology. To decipher their relative contributions requires the homogeneity afforded by population isolates. The Faroe Islands have excellent historical genealogy, elevated risk of PD and high exposure to environmental risk factors. Comparing and contrasting findings within and between family-based cohorts provides a unique opportunity.

Methods: Ongoing clinical research exams detail autonomic, cognitive, motor, psychiatric, sensory and sleep components of PD, and explore potential prodromal features in asymptomatic relatives. Our initial genetic approach has been to screen for pathogenic mutations in PD genes by targeted sequencing and genotyping, with additional genome-wide genotyping and exome sequencing efforts employing a number of analysis methods: disease segregation, coefficient of inbreeding, genome-wide homozygosity and screening copy number variants. Environmental research has explored exposure to persistent pollutants, e.g. polychlorinated biphenyls. Multivariate statistical methods are being used to assess the contribution of genetic and environmental factors on disease susceptibility and progression.

Results: As of January 2015, the Faroese cohort consists of 270 PD patients with clinical data, blood samples, detailed genealogic, lifestyle and environmental data available for ∼80%. Also 253 controls and 156 unaffected relatives have provided a blood sample and lifestyle and environmental data. Follow-up has been performed for 53 living patients and 46 unaffected relatives. Pedigrees have been constructed identifying two major clusters of increased incidence. Genome-wide genotyping (n=230) and exome sequencing (n=50) has been performed, and genealogies have been validated and refined using genetic markers, prepared for linkage and homozygosity analyses of PD and its trait components.

Conclusions: The Faroese Research Program offers a unique opportunity to study multiple aspects of PD risk and progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-faroese-parkinsons-diseases-research-program-multifactorial-analyses-of-a-complex-syndrome/