An exploratory study on the CHRNA3-CHRNA5-CHRNB4 cluster, smoking, and Parkinson's disease

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. Conclusion: This preliminary analysis does not support a relationship between these smoking-related GWAS SNPs and PD.