TY - JOUR
T1 - Do interactions between SNCA, MAPT, and LRRK2 genes contribute to Parkinson's disease susceptibility?
AU - Biernacka, Joanna M.
AU - Armasu, Sebastian M.
AU - Cunningham, Julie M.
AU - Eric Ahlskog, J.
AU - Chung, Sun Ju
AU - Maraganore, Demetrius M.
N1 - Funding Information:
The study was funded by the NIH grant 2R01ES10751 . We wish to thank the many research personnel who comprised the Molecular Epidemiology of Parkinson’s Disease research team (beyond the authors listed here). We especially wish to thank the many Parkinson’s disease patients, their siblings, and also the unrelated population controls for their participation in the study.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
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.
KW - Alpha-synuclein
KW - Gene-gene interaction
KW - Leucine rich repeat kinase 2
KW - Microtubule associated protein tau
KW - Parkinson's disease
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U2 - 10.1016/j.parkreldis.2011.07.001
DO - 10.1016/j.parkreldis.2011.07.001
M3 - Article
C2 - 21816655
AN - SCOPUS:81255127582
SN - 1353-8020
VL - 17
SP - 730
EP - 736
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 10
ER -