Original Investigation

Human Genetics

, Volume 123, Issue 3, pp 257-265

First online:

Exploring gene-environment interactions in Parkinson’s disease

  • Colin C. McCullochAffiliated withApplied Statistics Laboratory, General Electric Global Research Center
  • , Denise M. KayAffiliated withThe Genomics Institute, Wadsworth Center, New York State Department of Health
  • , Stewart A. FactorAffiliated withDepartment of Neurology, Emory University School of Medicine
  • , Ali SamiiAffiliated withDepartment of Neurology, University of Washington School of MedicineParkinson’s Disease Research Education and Clinical Center, VA Puget Sound Health Care System
  • , John G. NuttAffiliated withDepartment of Neurology, Oregon Health and Science University
  • , Donald S. HigginsAffiliated withParkinson’s Disease and Movement Disorder Clinic, Albany Medical Center
  • , Alida GriffithAffiliated withBooth Gardner Parkinson’s Care Center, Evergreen Hospital Medical Center
  • , John W. RobertsAffiliated withVirginia Mason Medical Center
  • , Berta C. LeisAffiliated withBooth Gardner Parkinson’s Care Center, Evergreen Hospital Medical Center
    • , Jennifer S. MontimurroAffiliated withThe Genomics Institute, Wadsworth Center, New York State Department of Health
    • , Cyrus P. ZabetianAffiliated withDepartment of Neurology, University of Washington School of MedicineParkinson’s Disease Research Education and Clinical Center, VA Puget Sound Health Care SystemGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System
    • , Haydeh PayamiAffiliated withThe Genomics Institute, Wadsworth Center, New York State Department of Health Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The objective of this study was to explore combined effects of four candidate susceptibility genes and two exposures on Parkinson’s disease (PD) risk; namely, α-synuclein (SNCA) promoter polymorphism REP1, microtubule-associated protein tau (MAPT) H1/H2 haplotypes, apolipoprotein E (APOE) ε2/ε3/ε4 polymorphism, ubiquitin carboxy-terminal esterase L1 (UCHL1) S18Y variant, cigarette smoking and caffeinated coffee consumption. 932 PD patients and 664 control subjects from the NeuroGenetics Research Consortium, with complete data on all six factors, were studied. Uniform protocols were used for diagnosis, recruitment, data collection and genotyping. A logistic regression model which included gene-exposure interactions was applied. Likelihood ratio tests (LRTs) were used for significance testing and Bayesian inference was used to estimate odds ratios (ORs). MAPT (P = 0.007), SNCA REP1 (P = 0.012), smoking (P = 0.001), and coffee (P = 0.011) were associated with PD risk. Two novel interactions were detected: APOE with coffee (P = 0.005), and REP1 with smoking (P = 0.021). While the individual main effects were modest, each yielding OR < 1.6, the effects were cumulative, with some combinations reaching OR = 12.6 (95% CI: 5.9–26.8). This study provides evidence for the long-held notion that PD risk is modulated by cumulative and interactive effects of genes and exposures. Furthermore, the study demonstrates that while interaction studies are useful for exploring risk relationships that might otherwise go undetected, results should be interpreted with caution because of the inherent loss of power due to multiple testing. The novel findings of this study that warrant replication are the evidence for interaction of coffee with APOE, and of smoking with REP1 on PD risk.