title: An exploratory study on the CHRNA3-CHRNA5-CHRNB4 cluster, smoking, and Parkinson's disease.
abstract: BACKGROUND
  Smokers have a lower risk of Parkinson's disease (PD). Recent genome-wide association studies (GWAS) have consistently linked several single nucleotide polymorphisms (SNPs) in the CHRNA3-CHRNA5-CHRNB4 cluster on chromosome 15.q25 to smoking behaviors and nicotine dependence. Investigations into these SNPs may help explain the nature and mechanisms of the smoking-PD relationship.
  
  
  OBJECTIVE
  To examine whether the genetic variations that were consistently associated with smoking or nicotine dependence in recent GWAS also predict the risk of PD.
  
  
  METHODS
  This is a population-based case-control study of 788 physician-diagnosed PD patients and 911 controls, all non-Hispanic Whites. Seven SNPs were selected based on findings from recent GWAS on smoking and nicotine dependence, all from the nicotinic acetylcholine receptor subunits (CHRN) A3-A5-B4. Odds ratios (ORs) and 95% confidence intervals were derived from logistic regression models under the assumption of logit-additive allelic effects.
  
  
  RESULTS
  Four SNPs in linkage disequilibrium from the CHRNA3-CHRNA5-CHRNB4 cluster were associated with smoking duration (OR >1.3, p < 0.05). However, none of the SNPs from this cluster was associated with PD risk in the overall analysis or after stratifying on smoking status.
  
  
  CONCLUSIONS
  This preliminary analysis does not support a relationship between these smoking-related GWAS SNPs and PD.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Clarice
authors.initials: C
authors.lastname: Weinberg
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
authors.forename: Yikyung
authors.initials: Y
authors.lastname: Park
authors.forename: Albert
authors.initials: A
authors.lastname: Hollenbeck
authors.forename: Aaron
authors.initials: A
authors.lastname: Blair
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Lauranell
authors.initials: L
authors.lastname: Burch
authors.forename: Honglei
authors.initials: H
authors.lastname: Chen
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human