ArticleHuman mutation2012
Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence of purifying selection and independent origin of the p.Arg1628Pro mutation in Europe.
Article in Human mutation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Widespread distribution of α-synuclein oligomers in LRRK2-related Parkinson's disease.Acta neuropathologica · 2025Article
- Mitochondrial Dysfunction and Parkinson's Disease: Pathogenesis and Therapeutic Strategies.Neurochemical research · 2023Review
- Precision Medicine in Parkinson's Disease: From Genetic Risk Signals to Personalized Therapy.Brain sciences · 2022Review
- Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.PLoS genetics · 2021Article
- Fine-mapping of the non-coding variation driving the Caucasian LRRK2 GWAS signal in Parkinson's disease.Parkinsonism & related disorders · 2021Article
- LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson's Disease Cohort from Kazakhstan.Parkinson's disease · 2020Article
- Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and corticobasal degeneration.Movement disorders : official journal of the Movement Disorder Society · 2017Article
- Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.Journal of neurochemistry · 2016Review
- Heterogeneity of leucine-rich repeat kinase 2 mutations: genetics, mechanisms and therapeutic implications.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
- The screening of the 3'UTR sequence of LRRK2 identified an association between the rs66737902 polymorphism and Parkinson's disease.Journal of human genetics · 2014Article
- Genetic insights into sporadic Parkinson's disease pathogenesis.Current genomics · 2013Article
- Parkinson's disease: from genetics to clinical practice.Current genomics · 2013Article
- Advances in the genetics of Parkinson disease.Nature reviews. Neurology · 2013Review
- LRRK2: cause, risk, and mechanism.Journal of Parkinson's disease · 2013Review
- Evolution of neurodegeneration.Current biology : CB · 2012Review
- Genetic Identification in Early Onset Parkinsonism among Norwegian Patients.Movement disorders clinical practiceArticle
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 3 countries.
Funding
Abstract
Genetic variation in LRRK2 predisposes to Parkinson disease (PD), which underpins its development as a therapeutic target. Here, we aimed to identify novel genotype-phenotype associations that might support developing LRRK2 therapies for other conditions. We sequenced the 51 exons of LRRK2 in cases comprising 12 common diseases (n = 9,582), and in 4,420 population controls. We identified 739 single-nucleotide variants, 62% of which were observed in only one person, including 316 novel exonic variants. We found evidence of purifying selection for the LRRK2 gene and a trend suggesting that this is more pronounced in the central (ROC-COR-kinase) core protein domains of LRRK2 than the flanking domains. Population genetic analyses revealed that LRRK2 is not especially polymorphic or differentiated in comparison to 201 other drug target genes. Among Europeans, we identified 17 carriers (0.13%) of pathogenic LRRK2 mutations that were not significantly enriched within any disease or in those reporting a family history of PD. Analysis of pathogenic mutations within Europe reveals that the p.Arg1628Pro (c4883G>C) mutation arose independently in Europe and Asia. Taken together, these findings demonstrate how targeted deep sequencing can help to reveal fundamental characteristics of clinically important loci.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.