Linked Life Data

18210157

Source:http://linkedlifedata.com/resource/pubmed/id/18210157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-19
pubmed:abstractText
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) epsilon2/epsilon3/epsilon4 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1432-1203
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-65
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18210157-Adult, pubmed-meshheading:18210157-Aged, pubmed-meshheading:18210157-Aged, 80 and over, pubmed-meshheading:18210157-Apolipoproteins E, pubmed-meshheading:18210157-Case-Control Studies, pubmed-meshheading:18210157-Environment, pubmed-meshheading:18210157-Genetic Predisposition to Disease, pubmed-meshheading:18210157-Genetic Variation, pubmed-meshheading:18210157-Genotype, pubmed-meshheading:18210157-Haplotypes, pubmed-meshheading:18210157-Humans, pubmed-meshheading:18210157-Male, pubmed-meshheading:18210157-Middle Aged, pubmed-meshheading:18210157-Parkinson Disease, pubmed-meshheading:18210157-Polymorphism, Genetic, pubmed-meshheading:18210157-Questionnaires, pubmed-meshheading:18210157-Risk Factors, pubmed-meshheading:18210157-Ubiquitin Thiolesterase, pubmed-meshheading:18210157-alpha-Synuclein, pubmed-meshheading:18210157-tau Proteins
pubmed:year
2008
pubmed:articleTitle
Exploring gene-environment interactions in Parkinson's disease.
pubmed:affiliation
Applied Statistics Laboratory, General Electric Global Research Center, Niskayuna, NY, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Multicenter Study, Research Support, N.I.H., Extramural