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

  • Skipper L
  • Li Y
  • Bonnard C
 et al. 
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Abstract

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.

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Authors

  • Lisa Skipper

  • Yi Li

  • Carine Bonnard

  • Ratnagopal Pavanni

  • Yuen Yih

  • Eva Chua

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