eQTL [136, 137, 135] variants mapped in blood vs. brain. Thus, when analyzing gene regulatory potential to study the neurobiology of addiction, it is critical to use disease-relevant brain tissue. Reliance on blood-specific regulatory effects could even lead to erroneous conclusions, as illustrated by the cis-eQTL SNP rs880395 having opposing directions of association with CHRNA5 expression in lymphoblastoid cell lines, as compared to frontal cortex [49]. Moreover, gene regulatory effects can differ across the different brain tissues, so comprehensive functional and regulatory assessment will require the availability of ‘omics data across multiple brain tissues, including ones traditionally viewed as being addiction-relevant (e.g., PFC, nucleus accumbens) and others often overlooked (e.g., cerebellum). GTEx, Brain eQTL Almanac, and others provide an unprecedented opportunity to carry out comprehensive analyses in normal brains. Future studies are needed for more thorough and well-powered assessment of brain tissues in participants with addiction phenotype data.
