Using data from over 18,000 patients, scientists have identified more than two dozen genetic risk factors involved in Parkinson's disease, including six that had not been previously reported. The study, published in Nature Genetics, was partially funded by the National Institutes of Health (NIH) and led by scientists working in NIH laboratories.

"Unraveling the genetic underpinnings of Parkinson's is vital to understanding the multiple mechanisms involved in this complex disease, and hopefully, may one day lead to effective therapies," said Andrew Singleton, Ph.D., a scientist at the NIH's National Institute on Aging (NIA) and senior author of the study.

Dr. Singleton and his colleagues collected and combined data from existing genome-wide association studies (GWAS), which allow scientists to find common variants, or subtle differences, in the genetic codes of large groups of individuals. The combined data included approximately 13,708 Parkinson's disease cases and 95,282 controls, all of European ancestry.

The investigators identified potential genetic risk variants, which increase the chances that a person may develop Parkinson's disease. Their results suggested that the more variants a person has, the greater the risk, up to three times higher, for developing the disorder in some cases.

"The study brought together a large international group of investigators from both public and private institutions who were interested in sharing data to accelerate the discovery of genetic risk factors for Parkinson's disease," said Margaret Sutherland, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH. "The advantage of this collaborative approach is highlighted in the identification of pathways and gene networks that may significantly increase our understanding of Parkinson's disease."

To obtain the data, the researchers collaborated with multiple public and private organizations, including the U.S. Department of Defense, the Michael J. Fox Foundation, 23andMe and many international investigators.

Affecting millions of people worldwide, Parkinson's disease is a degenerative disorder that causes movement problems, including trembling of the hands, arms, or legs, stiffness of limbs and trunk, slowed movements and problems with posture. Over time, patients may have difficulty walking, talking, or completing other simple tasks. Although nine genes have been shown to cause rare forms of Parkinson's disease, scientists continue to search for genetic risk factors to provide a complete genetic picture of the disorder.

The researchers confirmed the results in another sample of subjects, including 5,353 patients and 5,551 controls. By comparing the genetic regions to sequences on a state-of-the-art gene chip called NeuroX, the researchers confirmed that 24 variants represent genetic risk factors for Parkinson's disease, including six variants that had not been previously identified. The NeuroX gene chip contains the codes of approximately 24,000 common genetic variants thought to be associated with a broad spectrum of neurodegenerative disorders.

"The replication phase of the study demonstrates the utility of the NeuroX chip for unlocking the secrets of neurodegenerative disorders," said Dr. Sutherland. "The power of these high tech, data-driven genomic methods allows scientists to find the needle in the haystack that may ultimately lead to new treatments."

Some of the newly identified genetic risk factors are thought to be involved with Gaucher's disease, regulating inflammation and the nerve cell chemical messenger dopamine as well as alpha-synuclein, a protein that has been shown to accumulate in the brains of some cases of Parkinson's disease. Further research is needed to determine the roles of the variants identified in this study.

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This work was supported by NIA Intramural Research Program and grants from the NINDS (NS037167, NS071674, NS060113, NS036630, NS17950, NS070867, NS36960), the NIA (AG000949, AG000932, AG008122, AG016495, AG033193, AG031287, AG013846, AG025259, AG023629, AG024826) and the National Institute of Environmental Health Sciences NIEHS (ES101986).

Reference:

Nalls et al. "Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease" Nat. Genetics, July 27, 2014. DOI: 10.1038/ng3043

For more information about neurological disorders and the latest neuroscience research:

http://www. ninds. nih. gov/ disorders/ parkinsons_disease/ parkinsons_disease. htm

http://www. grc. nia. nih. gov/

Additional support was provided by the NIH, Department of Defense, the Michael J Fox Foundation for Parkinson's Research, American Parkinson Disease Association, Barnes Jewish Hospital Foundation, Hersenstichting Nederland, the Prinses Beatrix Fonds, the German Federal Ministry of Education, Science, Research and Technology, the German Federal Ministry of Education and Research, the State of Bavaria, the Initiative and Networking Fund of the Helmholtz Association, the French National Agency of Research, France-Parkinson Association, "Investissements d'avenir", Assistance Publique-Hôpitaux de Paris, the Landspitali University Hospital Research Fund, Icelandic Research Council, European Commission, University of Helsinki, Helsinki University Central Hospital, University of Eastern Finland, the Medical Research Council and Wellcome Trust, National Institute for Health Research (NIHR) Biomedical Research Centre, Parkinson's UK, Coriell Cell Repositories, the King Faisal Specialist Hospital and Research Centre, National Institute for Health Research (NIHR) Biomedical Research Centre, Cure Alzheimer's Fund (CAF), Prize4Life, the National Alliance for Research on Schizophrenia and Depression, EMD Serono, Fidelity Biosciences Research Initiative, the Parkinson's disease foundation, University of Thessaly,the Hellenic Secretariat of Research and Technology, GlaxoSmithKline Greece, the Bumpus foundation, the Internationaal Parkinson Fonds, Netherlands Organization for Scientific Research, Netherlands Organization for Health Research and Development, Parkinson's UK.

NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. It provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer's Disease Education and Referral (ADEAR) Center at http://www. nia. nih. gov/ Alzheimers . Information on health and on aging generally can be found at http://www. nia. nih. gov .