To evaluate the regulatory potential of novel intronic SNPs in CHRNA4 associated with nicotine dependence, we first used RNA-seq and genotype data from the pilot phase of the Genotype-Tissue Expression (GTEx) project to investigate SNP effects on splicing. GTEx captures a wide range of tissues collected post-mortem from donors of any age from 21 to 70 years old, sex and racial/ethnic group, although the data set is comprised mostly of European-ancestry participants.44, 45 Exclusions were made for HIV infection or high-risk behaviors, viral hepatitis, metastatic cancer, recent chemotherapy or radiation therapy, recent whole-blood transfusion or body mass index at the extremes. We focused on the liver tissue, which had the highest CHRNA4 expression levels among the GTEx tissues, and all brain tissues combined, which had lower CHRNA4 expression levels but high relevance for nicotine dependence.
