In this study we detected reproducible allelic expression of CHRNA5 mRNA in frontal cortex of African Americans, Australians and European Americans. Therefore, we used allelic mRNA expression imbalance as a phenotypic trait to identify functional cis-acting variants. In frontal cortices of European ancestry, subjects who were AEI-positive (ASE >2) detected by either rs16969968 or rs615470 are heterozygous for 13 of the 23 variants genotyped (Figures 2b and 3b). These 13 variants, flanked by rs12916483 and rs4275821, are in a >12 kb region spanning from upstream of the CHRNA5 transcription site (−8,521 bp relative to the AUG of CHRNA5) to upstream of the PSMA4 transcription start site (−358 bp relative to the AUG of PSMA4) (Table 1, Figure 5). Subjects who were AEI-negative (ASE <2) are homozygous for all 13 variants. The concordance of AEI-positive with heterozygosity suggests that the difference in mRNA expression is affected by variants in this region.
