Exploring gene-environment interactions in Parkinson's disease

被引:85
作者
McCulloch, Colin C. [2 ]
Kay, Denise M. [1 ]
Factor, Stewart A. [6 ]
Samii, Ali [3 ,4 ]
Nutt, John G. [8 ]
Higgins, Donald S. [7 ]
Griffith, Alida [9 ]
Roberts, John W. [10 ]
Leis, Berta C. [9 ]
Montimurro, Jennifer S. [1 ]
Zabetian, Cyrus P. [3 ,4 ,5 ]
Payami, Haydeh [1 ]
机构
[1] New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY 12201 USA
[2] Gen Elect Global Res Ctr, Appl Stat Lab, Niskayuna, NY USA
[3] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA
[4] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA
[5] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA
[6] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
[7] Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA
[8] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA
[9] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA
[10] Virginia Mason Med Ctr, Seattle, WA 98101 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1007/s00439-008-0466-z
中图分类号
Q3 [遗传学];
学科分类号
071007 [遗传学]; 090102 [作物遗传育种];
摘要
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, alpha-synuclein (SNCA) promoter polymorphism REP1, microtubule-associated protein tau (MAPT) H1/H2 haplotypes, apolipoprotein E (APOE) epsilon 2/epsilon 3/epsilon 4 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.
引用
收藏
页码:257 / 265
页数:9
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