Schizophrenia & Smoking Traits

Research Paper Title

Colocalisation of association signals at nicotinic acetylcholine receptor genes between schizophrenia and smoking traits.

Background

Epidemiological data suggest that smoking may be a risk factor for schizophrenia (SCZ), but more evidence is needed. Two regions coding nicotinic acetylcholine receptor (nAchR) subunits, atCHRNA2 and the CHRNA5/A3/B4 cluster, were associated with SCZ in genome-wide association studies (GWAS). Additionally, a signal at CHRNA4 is near significance. CHRNA2 was also associated with cannabis use disorder (CUD). These regions were also associated with smoking behaviours. If tobacco is a risk factor, the GWAS signals at smoking behaviours and SCZ have to be due to the same causal variants, i.e. they have to colocalise, although colocalisation does not necessarily imply causality. Here, we present colocalisation analysis at these loci between SCZ and smoking behaviours.

Methods

The Bayesian approach implemented in coloc was used to check for posterior probability of colocalisation versus independent signals at the three loci with some evidence of association with SCZ and smoking behaviours, using GWAS summary statistics. Colocalisation was also assessed for positive control traits and CUD. Three different sensibility analyses were used to confirm the results. A visualisation tool, LocusCompare, was used to facilitate interpretation of the coloc results.

Results

Evidence for colocalisation of GWAS signals between SCZ and smoking behaviours was found for CHRNA2. Evidence for independent causal variants was found for the other two loci. CUD GWAS signal at CHRNA2 colocalises with SCZ and smoking behaviours.

Conclusions

Overall, the results indicate that the association between some nAchR subunit genes and SCZ cannot be solely explained by their effect on smoking behaviours.

Reference

Al-Soufi, L. & Costas, J. (2021) Colocalization of association signals at nicotinic acetylcholine receptor genes between schizophrenia and smoking traits. Drug and Alcohol Dependence. doi: 10.1016/j.drugalcdep.2021.108517. Online ahead of print.

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