SynthesisMovement disorders : official journal of the Movement Disorder Society2022
Coding and Noncoding Variation in LRRK2 and Parkinson's Disease Risk.
Synthesis in Movement disorders : official journal of the Movement Disorder Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inflammatory bowel disease and risk of Parkinson's disease: evidence from a meta-analysis of 14 studies involving more than 13.4 million individuals.Frontiers in medicine · 2023Pooled it
- Association between cerebrospinal fluid LRRK2 and incident orthostatic hypotension differs by genetic background in Parkinson's disease.Acta neurologica Belgica · 2026Article
- Chemical Genetic Targeting of the LRRK2 GTPase Domain.bioRxiv : the preprint server for biology · 2026Article
- Addressing the Challenges of Translating LRRK2 Biology into Disease-Modifying Therapies: The LRRK2 Investigative Therapeutics Exchange Initiative.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Review
- The genetic spectrum of LRRK2 variants in Parkinson's disease: findings from a large Chinese cohort.NPJ Parkinson's disease · 2026Article
- LRRK2 as a Potential Disease-Modifying Target in Sporadic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis.Science advances · 2025Article
- Leucine-Rich Repeat Kinase 2 Relates to Neuroaxonal Degeneration via Tau Pathology and Microglial Activation in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.Acta neurologica Belgica · 2025Article
- Targeting specific kinase substrates rescues increased colitis severity induced by the Crohn's disease-linked LRRK2-N2081D variant.The Journal of clinical investigation · 2025Article
- Abundant non-inclusion α-synuclein pathology in Lewy body-negative LRRK2-mutant cases.Acta neuropathologica · 2025Article
- Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.Molecular neurobiology · 2024Review
- LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.Trends in molecular medicine · 2024Review
- Mechanisms of lysosomal tubulation and sorting driven by LRRK2.Biochemical Society transactions · 2024Review
- Single molecule array measures of LRRK2 kinase activity in serum link Parkinson's disease severity to peripheral inflammation.Molecular neurodegeneration · 2024Article
- The landscape of rare genetic variation associated with inflammatory bowel disease and Parkinson's disease comorbidity.Genome medicine · 2024Article
- Mutant LRRK2 exacerbates immune response and neurodegeneration in a chronic model of experimental colitis.Acta neuropathologica · 2023Article
- Regulation of LRRK2 mRNA stability by ATIC and its substrate AICAR through ARE-mediated mRNA decay in Parkinson's disease.The EMBO journal · 2023Article
- Proteome wide association studies of LRRK2 variants identify novel causal and druggable proteins for Parkinson's disease.NPJ Parkinson's disease · 2023Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundThe leucine-rich repeat kinase 2 (LRRK2) gene harbors both rare highly damaging missense variants (eg, p.G2019S) and common noncoding variants (eg, rs76904798) with lower effect sizes that are associated with Parkinson's disease (PD) risk.
objectivesThis study aimed to investigate in a large meta-analysis whether the LRRK2 Genome-Wide Association Study (GWAS) signal represented by rs76904798 is independently associated with PD risk from LRRK2 coding variation and whether complex linkage disequilibrium structures with p.G2019S and the 5' noncoding haplotype account for the association of LRRK2 coding variants.
methodsWe performed a meta-analysis using imputed genotypes from 17,838 patients, 13,404 proxy patients, and 173,639 healthy controls of European ancestry. We excluded carriers of p.G2019S and/or rs76904798 to clarify the role of LRRK2 coding variation in mediating disease risk and excluded carriers of relatively rare LRRK2 coding variants to assess the independence of rs76904798. We also investigated the co-inheritance of LRRK2 coding variants with p.G2019S, rs76904798, and p.N2081D.
resultsLRRK2 rs76904798 remained significantly associated with PD after excluding the carriers of relatively rare LRRK2 coding variants. LRRK2 p.R1514Q and p.N2081D were frequently co-inherited with rs76904798, and the allele distribution of p.S1647T significantly changed among patients after removing rs76904798 carriers.
conclusionsThese data suggest that the LRRK2 coding variants previously related to PD (p.N551K, p.R1398H, p.M1646T, and p.N2081D) do not drive the 5' noncoding GWAS signal. These data, however, do not preclude the independent association of the haplotype p.N551K-p.R1398H and p.M1646T with altered disease risk. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
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