The discovery of these new genetic risk factors is the result of a long and complex study that began in 2010 and has relied on the cooperation and pooling of resources across several international public and private institutions. The Institut du Cerveau – ICM is proud to have participated in this pivotal project; its contribution to enabling such a major scientific advancement reflects the institute’s international reputation and excellence in research.
As a means to develop effective new therapies for Parkinson’s, deciphering the genetic foundations of this complex disease is key. To share data and accelerate research on Parkinson’s genetic profile, Professor Alexis Brice’s team at the Institut du Cerveau – ICM joined the ranks of a scientific consortium bringing together public and private institutions across the globe. Launched in 2010, this ambitious project relied on the cooperation of various prominent organizations, including the US National Institute of Health (NIH), the US Department of Defense and the Michael J. Fox Foundation.
Aiming to decrypt Parkinson’s genetic profile, researchers collected and combined data from all existing “genome-wide association studies” (GWAS) on this pathology. GWAS consist of investigating subtle genetic differences called “genetic variants”, across the entire genome and across a large number of individuals with and without Parkinson’s. A correlation can thus be established between these genetic variants and the pathology. This colossal study combined data from over 100,000 people, including 13,708 Parkinson’s disease cases and 95,282 controls. The gathering and meta-analysis (a complex statistical approach) of data from this large-scale cohort allowed investigators to identify several genetic variants as potential risk variants for Parkinson’s. Indeed, further analysis suggested that the more these genetic variants a person has, the greater their risk for developing the disease.
After comparing the genetic variants from this meta-analysis to a “state-of-the-art” gene-chip specific to neurodegenerative pathologies (NeuroX chip), along with other complementary tests, scientists confirmed that 24 of these variants may be genetic risk factors for Parkinson’s disease, 6 of which are new. Interestingly, the other 18 genetic risk factors had previously been identified using other methods, confirming their association with the disease and validating the relevance of the methodology used.
Made possible through international collaboration, this high-tech, large-scale, data-driven genomic study has thus updated 6 new genetic risk factors for Parkinson’s disease.
These results represent a major scientific breakthrough in the unraveling of Parkinson’s genetic profile, required for understanding the onset of the disease in patients and developing new effective therapies.
The second most prevalent cause of motor disability, Parkinson’s disease affects 4 million people worldwide*. It is a neurodegenerative disorder that causes uncontrolled movements, 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 9 genes have been linked to rare forms of Parkinson’s disease, scientists continue to explore the human genome with the view of providing a comprehensive genetic profile of the disease.
Professor Alexis Brice’s team at the Institut du Cerveau – ICM studies the genetic, molecular and pathophysiological aspects of degenerative diseases, including Parkinson’s disease. Through its participation in the ambitious project of the large-scale meta-analysis of genome-wide association studies of Parkinson’s disease, the team hopes to discover new therapeutic targets in order to slow neurodegeneration brought on by this disease.
* Sources : OMS, ONU, INSERM, Fédération internationale de la Sclérose en Plaques, European Brain Council
Scientific article published in Nature Genetics on 27/07/2014: Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease
Mike A Nalls, Nathan Pankratz, Christina M Lill, Chuong B Do, Dena G Hernandez, Mohamad Saad, Anita L DeStefano, Eleanna Kara, Jose Bras, Manu Sharma, Claudia Schulte, Margaux F Keller, Sampath Arepalli, Christopher Letson, Connor Edsall, Hreinn Stefansson, Xinmin Liu, Hannah Pliner, Joseph H Lee, Rong Cheng, International Parkinson’s Disease Genomics Consortium (IPDGC), Parkinson’s Study Group (PSG) Parkinson’s Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), The Ashkenazi Jewish Dataset Investigator, Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE), North American Brain Expression Consortium (NABEC), United Kingdom Brain Expression Consortium (UKBEC), Greek Parkinson’s Disease Consortium, Alzheimer Genetic Analysis Group, M Arfan Ikram, John P A Ioannidis, Georgios M Hadjigeorgiou, Joshua C Bis, Maria Martinez, Joel S Perlmutter, Alison Goate, Karen Marder, Brian Fiske, Margaret Sutherland, Georgia Xiromerisiou, Richard H Myers, Lorraine N Clark, Kari Stefansson, John A Hardy, Peter Heutink, Honglei Chen, Nicholas W Wood, Henry Houlden, Haydeh Payami, Alexis Brice, William K Scott, Thomas Gasser, Lars Bertram, Nicholas Eriksson, Tatiana Foroud & Andrew B Singleton