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More than one in four Ashkenazi Parkinson’s patients carry genetic risk variant
Major global study finds Jewish patients could be particularly well placed to benefit from new targeted treatments
More than one in four Ashkenazi Jewish people with Parkinson’s disease carry a genetic variant linked to the condition, according to a major new international study.
The research found that 26.5 percent of Ashkenazi Jewish Parkinson’s patients studied carried either a mutation capable of causing the disease or a variant associated with an increased risk of developing it.
The findings could have important implications for genetic testing and future treatment, with two of the main genes involved already the focus of experimental therapies.
Published in The Lancet Neurology, the research examined genetic data from almost 100,000 people across 11 ancestral groups in the largest multi-ancestry study of Parkinson’s genetics conducted to date.
Among Ashkenazi Jewish patients, 10.7 percent carried a causal genetic variant – the highest rate found in any ancestral group in the study.
The figure was driven almost entirely by a variant in the LRRK2 gene, which is known to be relatively common in the Ashkenazi Jewish population.
Carrying the variant does not, however, mean someone will necessarily develop Parkinson’s. Some people with it never develop the disease, a phenomenon known as “reduced penetrance”.
When the study authors also included high-risk variants, primarily involving the GBA1 gene, the proportion of Ashkenazi Jewish Parkinson’s patients carrying an influential genetic risk factor rose to 26.5 percent.
Dr Lara M. Lange, the study’s first author, GP2 researcher and postdoctoral fellow at the National Institute on Ageing Laboratories of Neurogenetics, told Jewish News: “Our findings show that genetics play a remarkably strong role in Parkinson’s disease within the Ashkenazi Jewish community. More than one in four Ashkenazi Jewish Parkinson’s patients in our study carry a genetic variant linked to the disease.
“The encouraging news is that the primary genes of relevance, LRRK2 and GBA1, are the exact targets of exciting new precision therapies currently in clinical trials, putting this community in a prime position to benefit from the next generation of targeted, personalised treatments.”
The study authors said the concentration of genetic risk around particular LRRK2 and GBA1 variants could make genetic testing particularly useful for Ashkenazi Jewish patients.
Targeted screening can detect these variants and could give patients and their families more precise information about the genetic contribution to their disease, as well as helping to inform genetic counselling.
The findings could also make Ashkenazi Jewish patients particularly relevant to current and upcoming clinical trials, as experimental drugs are already being developed to target the proteins encoded by LRRK2 and GBA1.
The study authors also highlighted people who carry variants in both genes. Studying the “dual carriers”, they said, could offer important clues about how different genetic pathways interact and ultimately help scientists develop more personalised treatments targeting more than one pathway.
The wider study mapped genetic risk across populations around the world, highlighting significant differences between ancestral groups and the importance of greater diversity in Parkinson’s research.
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