TY - JOUR
T1 - Genetic susceptibility loci, environmental exposures, and Parkinson's disease
T2 - A case-control study of gene-environment interactions
AU - Chung, Sun Ju
AU - Armasu, Sebastian M.
AU - Anderson, Kari J.
AU - Biernacka, Joanna M.
AU - Lesnick, Timothy G.
AU - Rider, David N.
AU - Cunningham, Julie M.
AU - Ahlskog, J. Eric
AU - Frigerio, Roberta
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 - 2013/6
Y1 - 2013/6
N2 - Background: Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Methods: Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or " VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Results: Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. Conclusions: This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.
AB - Background: Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Methods: Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or " VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Results: Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. Conclusions: This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.
KW - Environment
KW - Genes
KW - Interactions
KW - Parkinson's disease
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U2 - 10.1016/j.parkreldis.2013.02.008
DO - 10.1016/j.parkreldis.2013.02.008
M3 - Article
C2 - 23507417
AN - SCOPUS:84891537762
SN - 1353-8020
VL - 19
SP - 595
EP - 599
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 6
ER -