Human Genetics

, Volume 123, Issue 3, pp 257–265

Exploring gene-environment interactions in Parkinson’s disease

  • Colin C. McCulloch
  • Denise M. Kay
  • Stewart A. Factor
  • Ali Samii
  • John G. Nutt
  • Donald S. Higgins
  • Alida Griffith
  • John W. Roberts
  • Berta C. Leis
  • Jennifer S. Montimurro
  • Cyrus P. Zabetian
  • Haydeh Payami
Original Investigation

DOI: 10.1007/s00439-008-0466-z

Cite this article as:
McCulloch, C.C., Kay, D.M., Factor, S.A. et al. Hum Genet (2008) 123: 257. doi:10.1007/s00439-008-0466-z
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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.

Supplementary material

439_2008_466_MOESM1_ESM.doc (108 kb)
(DOC 108 kb)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Colin C. McCulloch
    • 1
  • Denise M. Kay
    • 2
  • Stewart A. Factor
    • 6
  • Ali Samii
    • 3
    • 4
  • John G. Nutt
    • 8
  • Donald S. Higgins
    • 7
  • Alida Griffith
    • 9
  • John W. Roberts
    • 10
  • Berta C. Leis
    • 9
  • Jennifer S. Montimurro
    • 2
  • Cyrus P. Zabetian
    • 3
    • 4
    • 5
  • Haydeh Payami
    • 2
  1. 1.Applied Statistics LaboratoryGeneral Electric Global Research CenterNiskayunaUSA
  2. 2.The Genomics InstituteWadsworth Center, New York State Department of HealthAlbanyUSA
  3. 3.Department of NeurologyUniversity of Washington School of MedicineSeattleUSA
  4. 4.Parkinson’s Disease Research Education and Clinical CenterVA Puget Sound Health Care SystemSeattleUSA
  5. 5.Geriatric Research Education and Clinical CenterVA Puget Sound Health Care SystemSeattleUSA
  6. 6.Department of NeurologyEmory University School of MedicineAtlantaUSA
  7. 7.Parkinson’s Disease and Movement Disorder ClinicAlbany Medical CenterAlbanyUSA
  8. 8.Department of NeurologyOregon Health and Science UniversityPortlandUSA
  9. 9.Booth Gardner Parkinson’s Care CenterEvergreen Hospital Medical CenterKirklandUSA
  10. 10.Virginia Mason Medical CenterSeattleUSA