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New insights into the genetic architecture of Parkinsons disease

Scientists at the Hertie Institute for Clinical Brain Research and the University Hospital of Tübingen have as leaders of a large, international joint study demonstrated the significance of new genetic risk factors for Parkinsons disease in different population groups. The study is based on the genetic analysis of more than 17,000 patients and healthy control persons. As one of the largest genetic studies on Parkinsons disease to date, for the first time the study establishes the significance of risk genes in pathogenesis, not only for the inhabitants of the western hemisphere but also for the population in the Asia-Pacific region (Neurology 11.07.2012). Due to the rapid technical progress in genetic analyses large patient groups can be examined for risk genes for Parkinsons disease with relatively little time expenditure. In the process, Parkinsons patients are typically examined from specific regions, for example Western Europe or the USA, with the result that, to date, is was unclear whether and to what extent the risk factors found can be extrapolated to other population groups worldwide.

To tackle these problems, already in 2004, Tübingen physicians and researchers had founded a consortium, together with colleagues from the USA, for investigating the genetic-epidemiological causes of Parkinsons disease (GEO-PD). The current study was funded by the Michael J Fox Foundation (MJFF) and arose as part of this consortium in collaboration with Parkinsons specialists from 19 countries and four continents. The DNA samples collected in this way from over 17,000 patients and control persons have now made it possible for the first time to examine the results of large genome-wide association studies in different patient populations worldwide and to define their significance for their respective population. In doing so the study reveals the particular significance of the population-specific context in interpreting and evaluating genetic risk factors.

On the basis of the study, risk genes can be named for Parkinsons disease, which, via follow-up examinations on the affected carriers, allow predictions on the natural progression of the disease. This is a first step in the direction of future personalised risk modelling for carriers of the different gene variations.

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