Journal Article

Comprehensive evaluation of common genetic variation within <i>LRRK2</i> reveals evidence for association with sporadic Parkinson's disease

Lisa Skipper, Yi Li, Carine Bonnard, Ratnagopal Pavanni, Yuen Yih, Eva Chua, Wing-Kin Sung, Louis Tan, Meng-Cheong Wong, Eng-King Tan and Jianjun Liu

in Human Molecular Genetics

Volume 14, issue 23, pages 3549-3556
Published in print December 2005 | ISSN: 0964-6906
Published online November 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi376
Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease

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Parkinson's disease (PD) is a complex neurodegenerative disorder whose aetiologies are largely unknown. To date, mutations in six genes have been found causal for some rare familial forms of the disease and common variation within at least three of these is associated with the more common sporadic forms of PD. LRRK2 is the most recently identified familial PD gene, although its role in sporadic disease is unknown. In this study, we have performed the first comprehensive evaluation of common genetic variation within LRRK2 and investigated its contribution to risk of sporadic PD. We first characterized the linkage disequilibrium within LRRK2 using a panel of densely spaced SNPs across the gene. We then identified a subset of tagging-SNPs (tSNP) that capture the majority of common variation within LRRK2. Both single tSNP and tSNP haplotype analyses, using a large epidemiologically matched sporadic case–control series comprising 932 individuals, yielded significant evidence for disease association. We identified a haplotype that dramatically increases disease risk when present in two copies (OR=5.5, 95%CI=2.1–14.0, P=0.0001). Thus, we provide the first evidence that common genetic variation within LRRK2 contributes to the risk of sporadic PD in the Chinese population.

Journal Article.  4408 words.  Illustrated.

Subjects: Genetics and Genomics

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