Introducing the next gnomAD pre-print - in collaboration with
@23andMeResearch
we use highly curated genomic and phenotypic data from >4 million individuals to characterise the effects of life-long LRRK2 reduction in 1,358 loss-of-function carriers: 1/5
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Motivation: Gain-of-kinase function variants in LRRK2 are a frequent cause of Parkinson's disease, suggesting targeting LRRK2 as a promising therapeutic. Early studies in model organisms, however, show inconsistent phenotypes and raised concerns about toxicity 2/5
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We show that natural LoF carriers do not have reduced life expectancy, are not outliers for any blood biomarkers and do not show an over-representation of any adverse phenotypes, suggesting that therapeutically reducing LRRK2 in humans should be tolerated 3/5
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Not only are our results promising for the treatment of Parkinson's disease, they also demonstrate how large genetically and phenotypically characterised cohorts can be harnessed to inform drug discovery 4/5
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This work was co led with
@imarmean
and
@aaronkleinman
, masterminded by
@dgmacarthur
and Paul Cannon, and held together through the patience of the amazing
@Jalfoldi
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