Gene-Environment Interaction in PD: Predicting the Onset, Prognosis and Response to Treatment
Edmond J. Safra Global Genetics Consortia, 2004
Parkinson's disease is a complex and heterogeneous disorder. Discovery of genes that result in rare inherited forms of PD has led to new insights into the cause of disease and the promise of effective treatment. The cause of common forms of PD remains elusive, although there is strong evidence for the involvement of both genetic and environmental factors.
This MJFF grant will establish a global consortium to investigate the effects of genes and environmental exposures on PD, in the framework of prevention. The study will be powered by an unprecedented large sample size, and uniform clinical, genetic and epidemiological data. The aim is to identify the combinations of genotypes and exposures that are associated with protection against PD. We hope that the results will provide solid leads to pursue in research and in clinical trials for prevention and treatment.
Dr. Payami and colleagues formed the NeuroGenetics Research Consortium (NGRC) and recruited over 4,000 PD patients and controls from four U.S. investigator sites. Initially, as set by the aims of MJFF grant, they studied four genes and three environmental factors (cigarette smoking, coffee drinking and anti-inflammatory drug use) and showed that while each of the factors had a very modest effect individually, together they affected PD risk by more than 12-fold.
Although MJFF funding ended in 2006, NGRC continues to be maintained at a high level of productivity. A genome-wide gene-environment interaction study is under way and a genome-wide pharmacogenomics study is pending. The collaboration has been expanded, enrollment continued and subjects genetically characterized. Currently, NGRC includes investigators at seven academic institutions, two federal agencies, one state agency and a nonprofit organization. The consortium works with eight neurology clinics in four U.S. states and 6,000 research volunteers. Its resources encompass 10,000 DNA samples banked at two secure locations and a centralized database housing clinical, environmental, genetic and demographic data. NGRC openly collaborates with researchers worldwide and has helped several investigators obtain research grants.
MJFF funding resulted in publications in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Annals of Neurology, European Journal of Neurology, Movement Disorders and Human Genetics. Additionally, follow-on funding has been obtained from the National Institute of Neurological Disorders and Stroke (NINDS) (National Institutes of Health), the New York State Attorney General’s Office, NYSTEM – New York State Stem Cell Science and the Department of Veterans Affairs. Additional follow-on funding is pending from NINDS.
Research Scientist and Professor of Molecular Genetics at Genomics Institute