https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27974
One question I frequently get asked is "doctor, please tell me, is it genetic?"... I am instantly caught in conflict between offering swift reassurance because I know what people really mean is "will I pass this on to my children?" OR a providing a rather convoluted explanation along the lines of 'yes in some ways Parkinson's is genetic but because of a whole range of genetic factors affect one's risk of getting Parkinson's just a little bit'.
The truth is that most complex diseases are genetically determined to some extent and Parkinson's is a good example. That doesn't mean that if you have Parkinson's your relatives will definitely also get Parkinson's, but they might be at slightly higher risk. The strength of the genetic factors that they have and the combination of factors adjust the overall risk in individuals.
This offering from the IPDGC is an example of how different genetic factors combine...
LRRK2 is the commonest genetic cause of Parkinson's that we know about. Having a mutation in LRRK2 causes Parkinson's in about 30% of carriers in their later years. These mutations have a 50% chance of being passed on to the next generation, who then in turn also have about 30% chance of showing signs of Parkinson's in their later years. What determines the chance of showing signs of Parkinson's? Well at least in part it is likely due to the other genetic risk factors that you have.
In this paper, the authors show that having other genetic risk factors for Parkinson's (combined in a score) affects how likely carriers of LRRK2 mutations are to show signs of Parkinson's and that on average they tend to show them earlier in life.
Why is this important? LRRK2 drugs are being tested to see how they might protect people carrying mutations of LRRK2 against getting Parkinson's. It is likely that the combination of other genetic factors that people have will help select groups for trials and might also affect the response to treatment. This kind of research gets a little bit closer to realistic precision medicine for Parkinson's
Alastair Noyce
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