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. 2009 Jul;73(Pt 4):391-403.
doi: 10.1111/j.1469-1809.2009.00524.x. Epub 2009 May 21.

Parkinson's disease and low frequency alleles found together throughout LRRK2

Coro Paisán-Ruiz  1 , Nicole Washecka, Priti Nath, Andrew B Singleton, Elizabeth H Corder
Affiliations

Parkinson's disease and low frequency alleles found together throughout LRRK2

Coro Paisán-Ruiz et al. Ann Hum Genet. 2009 Jul.

Abstract

Mutations within LRRK2, most notably p.G2019S, cause Parkinson's disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. >50% likeness to one set). Set I, affected, carried certain low frequency alleles located in multiple functional domains. Set II was unaffected. Set III, also affected, resembled set II except for slightly elevated frequencies of minor alleles not defining set I. We conclude that certain low frequency alleles distributed throughout LRRK2 are a genetic background to a third of cases, defining a distinct subset.

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Figures

Figure 1
Figure 1. Minor allele frequencies
The frequency of minor alleles is shown for PD cases like (> 50% match, i.e. a membership score of 0.50 or higher) pattern I (n=91), control subjects like pattern II (n=250), and PD cases like pattern III (n=178).
See this image and copyright information in PMC

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