A recent study has discovered that more than a quarter of Ashkenazi Jews with Parkinson’s disease carry variants of genes either tied to causing the disease or associated with a higher risk of developing it.
The study, conducted by the Global Parkinson’s Genetics Program (GP2) and published in The Lancet Neurology, looked at the genetic architecture of Parkinson’s disease across participants of 11 different ancestries, making it the largest-ever global assessment of the genetic spectrum of the condition.
It found that 26.5 per cent of Ashkenazi Jews with Parkinson’s carried gene variants that made them more susceptible to the neurological condition.
Almost 100,000 people participated in the study – nearly 60,000 Parkinson’s patients and just in excess of 40,000 healthy control subjects.
Of this number, 2,343 of those with Parkinson’s were Ashkenazi Jewish, alongside 913 Ashkenazi Jewish control subjects.
The study aimed to assess the distribution of “causal variants” – genetic mutations linked to the causation of Parkinson’s disease – across diverse populations.
It also looked at “risk variants” – variants or genes associated with an increased risk of developing the disease.
It concluded that 10.7 per cent of Ashkenazi Jews with Parkinson’s disease carried a causal variant – the highest percentage of any ancestry and significantly higher than the 2.1 per cent of those with Parkinson’s found to have a causal variant across the study.
In all, researchers identified causal or risk variants in 26.5 per cent of the Ashkenazi Jewish Parkinson’s patients who participated in the study, the third highest percentage of any ancestry.
The study acknowledged that “genetic factors substantially contribute to Parkinson’s disease risk and progression” and aimed to advance scientific understanding of this.
The authors added that studies such as theirs were “crucial to improve diagnostic accuracy, enhance our understanding of disease mechanisms across populations, and ensure equitable application of and access to emerging genetically informed therapies”.
The study focused on variants in 16 different genes linked to autosomal-dominant Parkinson’s disease, autosomal-recessive Parkinson’s disease and atypical or complex parkinsonism – a group of progressive, neurodegenerative disorders that mimic standard Parkinson’s disease but progress more rapidly and feature additional neurological changes.
Across the study, causal and risk variants of the GBA1 and LRRK2 genes were the most common, but both were particularly prevalent in Ashkenazi Jewish Parkinson’s patients. Variants in the GBA1 gene were observed in 16.8 per cent of Ashkenazi Jewish patients, and variants of the LRRK2 gene were observed in 10.7 per cent of them. Twenty-five Ashkenazi Jewish patients (just over one per cent) were dual GBA1-LRRK2 carriers.
The study also found that individuals with the GBA1 risk variant showed a significantly earlier median age at onset of Parkinson’s across multiple ancestries and that 24.7 per cent of Ashkenazi Jews with Parkinson’s had a family history of the disease, compared to 3.4 per cent of Ashkenazi Jewish control subjects.
However, carrying a causal or risk variation does not necessarily indicate that a person will develop Parkinson’s disease, as the study found that 10.4 per cent of Ashkenazi Jewish control subjects carried causal or risk variants of the GBA1 or LRRK2 genes.
Encouragingly, the genetic variants most common in Ashkenazi Jews with Parkinson’s are those that are typically targeted in clinical trials and experimental therapies.
The researchers said: “Understanding ancestral diversity is crucial to improving diagnostic accuracy, enhancing understanding of disease mechanisms across populations, and ensuring equitable application of and access to emerging genetically informed therapies.”
They called for “systematic, large-scale, multi-ancestry investigations” to develop scientific understanding of the genetic architecture of Parkinson’s.
“Addressing current gaps in data diversity and global genetic representation is not optional but fundamental to translating genetic discovery into effective and inclusive genetically informed therapies in Parkinson’s disease on a global scale,” they wrote.
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