Among the brain tissues analysed in GTEx (https://gtexportal.org/home/) the index variant rs56372821 was found to be a strong eQTL for CHRNA2 in cerebellum (P-value in GTEx=2.1x10−7), with the risk allele (rs56372821-G) being associated with decreased expression of the gene (Supplementary Figure 2). CHRNA2 is expressed in the brain and encodes the neuronal acetylcholine receptor (nAChR) alpha-2 subunit, which is incorporated in heteropentameric neuronal nAChRs mainly with the beta-2 or beta-4 subunits23. Candidate gene studies of common variants have linked this gene to e.g. substance abuse24 and nicotine dependence25 but no genome-wide significant findings have connected CHRNA2 to any substance abuse or psychiatric disorder, besides a fuctional link between schizophrenia risk variants and CHRNA2 expression identified by Won et al26 (described below).
