Testing association between LRRK2 and Parkinson’s disease and investigating linkage disequilibrium
- C Paisán-Ruíz1,
- E W Evans1,
- S Jain1,
- G Xiromerisiou1,
- J R Gibbs1,
- J Eerola3,
- V Gourbali2,
- O Hellström4,
- J Duckworth1,
- A Papadimitriou2,
- P J Tienari3,
- G M Hadjigeorgiou2,
- A B Singleton1
- 1Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35 Room 1A1000 MSC 3707, 9000 Rockville Pike, Bethesda, MD 20892, USA
- 2Neurogenetics Unit, Department of Neurology, Medical School, University of Thessaly, Larissa, Greece
- 3Department of Neurology, Helsinki University Central Hospital and University of Helsinki, Biomedicum-Helsinki, Neuroscience Programme, Helsinki, Finland
- 4Department of Neurology, Seinäjoki Central Hospital, Seinäjoki, Finland
- Correspondence to: A B Singleton Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35 Room 1A1000 MSC 3707, 9000 Rockville Pike, Bethesda, MD 20892, USA;
- Accepted 28 July 2005
- Revised 27 July 2005
Background: We and others recently identified the gene underlying PARK8 linked Parkinson’s disease (PD). This gene, LRRK2, contains mutations that cause an autosomal dominant PD, including a mutation, G2019S, which is the most common PD causing mutation identified to date. Common genetic variability in genes that contain PD causing mutations has previously been implicated as a risk factor for typical sporadic disease.
Methods: We undertook a case-control association analysis of LRRK2 in two independent European PD cohorts using 31 tagging single nucleotide polymorphisms (tSNPs) and five potentially functional SNPs. To assess the structure of this locus in different populations, we have performed linkage disequilibrium (LD) analysis using these variants in a human diversity panel.
Results: We show that common genetic variability in LRRK2 is not associated with risk for PD in the European populations studied here. We also show inter-population variability in the strength of LD across this locus.
Conclusions: To our knowledge this is the first comprehensive analysis of common variability within LRRK2 as a risk factor for PD.
- LD, linkage disequilibrium
- PD, Parkinson’s disease
- SNP, single nucleotide polymorphism
- tSNP, tagging SNP
This research was supported in part by the Helsinki University Central Hospital, the Finnish Cultural Foundation, the Finnish Medical Foundation, and the Finnish National Graduate School of Clinical Investigation. It was also supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.
Competing interests: none declared