Until recently, environmental factors were thought to be wholly responsible for Parkinson's disease (PD). Since 2007 six genetic variants or 'loci' have been implicated that affect risk of developing the condition. In an Article published Online First and in an upcoming Lancet, researchers identify a further five loci, The Article presents work from a worldwide collaboration between investigators in the UK, USA, Germany, France, The Netherlands and Iceland. These efforts were led by Dr Andrew Singleton, National Institute on Aging at the National Institutes of Health, Bethesda, MD, USA, and Dr Nick Wood, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK, and colleagues from the International Parkinson Disease Genomics Consortium.
In what they describe as the largest genetic analysis of PD ever undertaken, the researchers did a meta-analysis of five genome-wide association studies (GWAS) from the USA and Europe covering some 7.7 million possible genetic variants. Common variants previously identified in the MAPT and SNCA genes alone were shown to contribute the majority of the estimated genetic risk identified. The researchers found that the 20% of patients with the highest number of risk variants at the 11 identified loci were two-and-a-half times more likely to develop PD than the 20% possessing the least number of genetic risk factors. Although this is substantively more genetic risk than has been shown for PD than before, the authors caution that these risk profiles are not yet of clinical validity, but reason that these data highlight new genes to focus in on as players in the development of PD.
The authors describe their findings as a launching point into further investigations into the pathophysiology of this debilitating condition. They say : "This study provides evidence that common genetic variation plays an important part in the cause of Parkinson's disease. We have confirmed a strong genetic component to Parkinson's disease, which, until recently, was thought to be completely caused by environmental factors."
They conclude: "The identification of additional common and rare risk variants for Parkinson's disease will probably revise our estimate of the genetic component of disease upward."
In a linked Comment, Dr Christine Klein and Dr Andreas Ziegler, University of Lübeck, Germany, say: "The Consortium's confirmation and discovery of potentially causal SNPs for the disease hold great promise for establishing causal hypotheses. This landmark study also serves another important purpose in that it provides a comprehensive stock-check on where we stand on our way towards clinical use of GWAS data in Parkinson's disease."
Dr Andrew Singleton, National Institute on Aging at the National Institutes of Health, Bethesda, MD, USA. Please contact Peggy Vaughn or Barbara Cire T) +1 301-496-1752 E) Nianews3@mail.nih.gov / singleta@mail.nih.gov Dr. Nick Wood, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK T) +44 20 7837 3611 extn 4255 E) nwood@ion.ucl.ac.uk
Dr Christine Klein, University of Lübeck, Germany. T) +49-451-2903353 E) christine.klein@neuro.uni-luebeck.de
For full Article and Comment see: http://press.thelancet.com/parkgenes.pdf
Notes to editors:
Additional contacts:
Dr. Thomas Gasser, Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen and DZNE – German Center for Neurodegenerative diseases, Germany, T) +49 7071 2986529 E) thomas.gasser@uni-tuebingen.de
Dr. Alexis Brice, Université Pierre et Marie Curie-Paris, INSERM, CNRS, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France. T) +33-(0)1-57-27-46-82, E) alexis.brice@upmc.fr
Dr. Peter Heutink, Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands. T) +31-205989962 E) P.Heutink@vumc.nl
Kari Stefansson, Sturlugata 8, 101 Reykjavík Iceland. E) kari.stefansson@decode.is T) 354-5701900
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