Objective/Rationale:
We will take advantage of the large European Prospective Investigation in Cancer (EPIC), a unique resource involving almost 500,000 participants from 10 European countries, with extensive and diverse dietary, lifestyle and other environmental information collected at least a decade before PD disease onset to (1) investigate environmental factors shown to be associated with PD and explore additional environmental risk factors; (2) explore the relationship of PD with other diseases, such as cancer, diabetes and cardiovascular diseases; and (3) perform epidemiological and genetic analyses including gene-environment interaction studies.
Project Description:
We estimate that there are currently ~ 1200 patients in EPIC.
The first stage of the study will aim at ascertaining PD cases. A three step approach will be used to maximize the accuracy and specificity of data. (1) Record linkage (hospital records, drug registries, etc) to identify all possible PD cases; (2) record review by neurologists, to confirm diagnosis (probable and definite) and collect additional clinical information on non motor features, dementia, etc; (3) quality control of case reviews.
We will then perform genome-wide genetic scanning using a PD-DNA chip kindly provided by 23andMe (>600,000 DNA markers across the genome). This dataset will be compared with a control dataset using a similar chip.
Finally, we will perform extensive epidemiological and genetic analyses with an emphasis on interactions between genes and environmental factors.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
Better understanding of the interactions between genes and the environment leading to Parkinson’s disease (PD) is a pre-requisite for the discovery of new treatments that will stop or slow the disease.
New genetic tools and technologies have revealed some genetic factors in PD, and epidemiological studies have suggested a number of environmental factors, as being pathogenic or protective.
With its wealth of unbiased information, collected at least a decade before disease onset, EPIC is a unique resource to investigate known and new environmental factors that may provide further insight into causes of PD and pave the way for new therapies.
Anticipated Outcome:
EPIC has been successful in revealing risk factors for cancer, with over 390 scientific publications to date. Key examples include the role of fibers and meat consumption in colorectal cancer, passive smoking in lung cancer and other pulmonary conditions and the association between sex steroids and breast cancer. We expect that our study will result in equally important new information on risk factors leading to PD.
Progress Report
The aims of our study is two-folds: Firstly, to use the very large European Prospective Investigation into Cancer (EPIC) to study the way that constitutional, genetic and environmental exposures interact to cause Parkinson’s disease. EPIC involves 520,000 volunteers in 23 centers across 10 European countries. EPIC is unique in the wealth of the demographic, diet, physical activity and other lifestyle factors and environmental exposures collected in a standardized fashion in the 90s, i.e. at least 10-20 years prior to Parkinson’s disease onset. We plan to perform a Genome Wide Association Study, using a custom made (for PD research only) chip, kindly donated by 23andMe that includes over1 million genetic markers, many directly linked to genes that have been implicated in PD.
Secondly, we are conducting a study on brain tissues donated by 450 PD patients in the United Kingdom during their lifetime for PD research to investigate the genetic, neuro-pathological and clinical characteristics of Parkinson’s disease patients who have developed cognitive impairment and dementia, in addition to their motor and other symptoms. We will attempt to identify the mechanisms and predictive markers of developing dementia and to contribute towards the prevention or development of new treatments for this condition.