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The study authors looked to systematically assess variation within the LRRK2 gene in individuals with and without Parkinson’s disease.

The researchers systematically identified genetic variation within the exons of the LRRK2 gene based on existing published research as well as unpublished findings from within the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping of 121 polymorphisms was conducted in three different populations: 6995 white cases and 5595 white controls, 1376 Asian cases and 962 Asian controls, and 240 Arab-Berber cases and 372 Arab-Berber controls.

New risk variants were identified in the white (M1646T variant) and Asian (A419V variant) populations. The same protective haplotype (N551K-R1398H-K1423K) was identified across all three populations. In the Asian population, one of two previously reported variants was also confirmed. 

The authors state that this study shows how “several rare and common genetic variants in the same gene can have independent effects on disease risk” and that this type of large-scale international collaboration is required to determine the pathogenicity, frequency and disease contribution in different populations.

The accompanying comment in The Lancet Neurology highlights some caveats in interpretation such as the sole use of exonic variants in this study as well as the need for further replication. The study also failed to identify around a third of the variants tested for, which as the authors state shows the “importance of studying genetic variability in large samples and in different ethnic groups, because frequencies and genetic effects might vary substantially”. Much work is still required to turn this knowledge of LRRK2 variants as potentially viable drug targets into therapies that may one day benefit patients.