To further evaluate the regulatory potential of novel nicotine dependence-associated SNPs, we conducted in silico testing of SNP associations with transcript-level CHRNA4 mRNA expression using the Brain expression quantitative trait loci (eQTL) Almanac.46 This resource contains genome-wide cis-eQTL results, which were generated using Illumina Omni1-Quad and Immunochip SNP genotypes, followed by 1000 Genomes imputation and mRNA expression levels from Affymetrix Human Exon 1.0 ST arrays on 134 European-ancestry participants in the UK Brain Expression Consortium data set.46 The participants, mostly adults, were free of neurodegenerative disorders and were collected irrespective of nicotine dependence or any other substance phenotype. Transcript-level and exon-level expression measurements were made across 10 regions of the post-mortem brain samples: cerebellar cortex, frontal cortex, hippocampus, inferior olivary nucleus (sub-dissected from the medulla), occipital cortex, putamen (at the level of the anterior commissure), substantia nigra, temporal cortex, thalamus (at the level of the lateral geniculate nucleus) and intralobular white matter. In addition to the single CHRNA4 transcript probe, probes were available in each of the exons for the transcripts that provide templates for a full-length CHRNA4 protein; no probe was available for the ancillary exon 4.1 of the alternative transcript that results in a truncated protein.
