Dataset Information

LRRK2 variation and Parkinson's disease in African Americans.

ABSTRACT: The global impact of LRRK2 mutations is yet to be realized with a lack of studies in specific ethnic groups, including those of Asian and African descent. Herein, we investigated the frequency of common LRRK2 variants by complete exon sequencing in a series of publicly available African American Parkinson's disease patients. Our study identified three novel synonymous exonic variants and 13 known coding variations; however, there did not appear to be any frequent (>5%) pathogenic mutations. Given the ethnic-specific LRRK2 variation previously identified in PD further studies in under-represented populations are warranted.

SUBMITTER: Ross OA

PROVIDER: S-EPMC2939165 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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LRRK2 variation and Parkinson's disease in African Americans.

Ross Owen A OA Wilhoite Greggory J GJ Bacon Justin A JA Soto-Ortolaza Alexandra A Kachergus Jennifer J Cobb Stephanie A SA Puschmann Andreas A Vilariño-Güell Carles C Farrer Matthew J MJ Graff-Radford Neill N Meschia James F JF Wszolek Zbigniew K ZK

Movement disorders : official journal of the Movement Disorder Society 20100901 12

The global impact of LRRK2 mutations is yet to be realized with a lack of studies in specific ethnic groups, including those of Asian and African descent. Herein, we investigated the frequency of common LRRK2 variants by complete exon sequencing in a series of publicly available African American Parkinson's disease patients. Our study identified three novel synonymous exonic variants and 13 known coding variations; however, there did not appear to be any frequent (>5%) pathogenic mutations. Give ...[more]

PMID: 20669299

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Project description: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.

Dataset Information

LRRK2 variation and Parkinson's disease in African Americans.

Publications

LRRK2 variation and Parkinson's disease in African Americans.

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