Do interactions between SNCA, MAPT, and LRRK2 genes contribute to Parkinson's disease susceptibility?

Joanna M Biernacka, Sebastian M. Armasu, Julie M Cunningham, J. Eric Ahlskog, Sun Ju Chung, Demetrius M. Maraganore

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Polymorphisms in SNCA, MAPT and LRRK2 genes have recently been confirmed as risk factors for Parkinson's disease (PD), although with small individual attributable risk. Here we investigated the association of PD with interactions between variants of these genes. Methods: As part of a previous study of PD susceptibility genes 119 SNCA, MAPT, and LRRK2 haplotype tagging single nucleotide polymorphisms (SNPs) and two variable number tandem repeats (VNTRs) were genotyped in 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Twenty-six of these SNPs were selected for SNP-SNP (or SNP-VNTR or VNTR-VNTR) interaction analysis (256 interaction pairs). Case-control analyses were performed to study association of pairwise SNP interactions with PD susceptibility. Results: Out of the 256 interaction pairs investigated, 10 had uncorrected p-values <0.05. These represented six SNCA- LRRK2 pairs, three SNCA- MAPT pairs, and one MAPT- LRRK2 pair. However, none of these pairwise interactions were significant after correction for multiple testing. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not reveal any significant interactions after accounting for multiple testing. Conclusions: This study provides no statistically significant evidence of gene-gene interaction effects for the three confirmed genetic susceptibility loci for PD. However, this does not exclude the possibility that other genomic loci or environmental risk factors interact with these genes.

Original languageEnglish (US)
Pages (from-to)730-736
Number of pages7
JournalParkinsonism and Related Disorders
Volume17
Issue number10
DOIs
StatePublished - Dec 2011

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Disease Susceptibility
Single Nucleotide Polymorphism
Parkinson Disease
Minisatellite Repeats
Genes
Genetic Loci
Genetic Predisposition to Disease
Age of Onset
Haplotypes

Keywords

  • Alpha-synuclein
  • Gene-gene interaction
  • Leucine rich repeat kinase 2
  • Microtubule associated protein tau
  • Parkinson's disease

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Do interactions between SNCA, MAPT, and LRRK2 genes contribute to Parkinson's disease susceptibility? / Biernacka, Joanna M; Armasu, Sebastian M.; Cunningham, Julie M; Eric Ahlskog, J.; Chung, Sun Ju; Maraganore, Demetrius M.

In: Parkinsonism and Related Disorders, Vol. 17, No. 10, 12.2011, p. 730-736.

Research output: Contribution to journalArticle

Biernacka, Joanna M ; Armasu, Sebastian M. ; Cunningham, Julie M ; Eric Ahlskog, J. ; Chung, Sun Ju ; Maraganore, Demetrius M. / Do interactions between SNCA, MAPT, and LRRK2 genes contribute to Parkinson's disease susceptibility?. In: Parkinsonism and Related Disorders. 2011 ; Vol. 17, No. 10. pp. 730-736.
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AB - Background: Polymorphisms in SNCA, MAPT and LRRK2 genes have recently been confirmed as risk factors for Parkinson's disease (PD), although with small individual attributable risk. Here we investigated the association of PD with interactions between variants of these genes. Methods: As part of a previous study of PD susceptibility genes 119 SNCA, MAPT, and LRRK2 haplotype tagging single nucleotide polymorphisms (SNPs) and two variable number tandem repeats (VNTRs) were genotyped in 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Twenty-six of these SNPs were selected for SNP-SNP (or SNP-VNTR or VNTR-VNTR) interaction analysis (256 interaction pairs). Case-control analyses were performed to study association of pairwise SNP interactions with PD susceptibility. Results: Out of the 256 interaction pairs investigated, 10 had uncorrected p-values <0.05. These represented six SNCA- LRRK2 pairs, three SNCA- MAPT pairs, and one MAPT- LRRK2 pair. However, none of these pairwise interactions were significant after correction for multiple testing. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not reveal any significant interactions after accounting for multiple testing. Conclusions: This study provides no statistically significant evidence of gene-gene interaction effects for the three confirmed genetic susceptibility loci for PD. However, this does not exclude the possibility that other genomic loci or environmental risk factors interact with these genes.

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