Although post-mortem brain samples and models based on cultured human brain cells provide a reliable approach to investigate the human transcriptome, investigation of peripheral tissues can permit studies of larger samples. In a blood-based transcriptome-wide study, 132 of 18,238 genes tested were differentially expressed between current smokers and never smokers and the loci identified were involved in the immune system, blood coagulation, natural killer cell, and cancer pathways158. By comparing former smokers with current and never-smokers, it was possible to distinguish different status: reversible for 94 genes, slowly reversible for 31 genes, and irreversible for 6 genes158. In the adipose tissue of 542 healthy female twins, DNA methylation and gene expression changes were observed in five genes (AHRR, CYP1A1, CYP1B1, CYTL1, and F2RL3) in response to tobacco smoking159. Based on neonatal umbilical cord blood, prenatal smoking was associated with the transcriptomic downregulation of fetal brain regulatory genes (BDNF, PLP1, and MBP) in active-smoker mothers but not among passive smokers160. In prospectively collected saliva samples, prenatal opioid exposure was associated with sex-dependent effects on hypothalamic feeding regulatory genes (DRD2 and NPY2R) with correlations with neonatal opioid withdrawal syndrome including hyperphagia and severity of withdrawal state161.
