Circadian Clock Gene Polymorphisms in Alcohol Use Disorders and Alcohol Consumption

Aims: Circadian clock genes are involved in the development of drug-induced behaviors and regulate neurotransmission pathways in addiction. Our aim was to study whether circadian clock gene polymorphisms predispose to alcohol dependence or abuse or other alcohol-related characteristics. Methods: The study sample comprised of 512 individuals having alcohol dependence or alcohol abuse (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)) and their 511 age- and sex-matched controls. This population-based sample was drawn from a cohort (n = 7415), representative of the Finnish general population aged 30 and over. Altogether 42 single-nucleotide polymorphisms of 19 genes related to the circadian pacemaker system were genotyped. Results: ARNTL rs6486120 T+ allelic status (P = 0.0007, q = 0.17), ADCYAP1 rs2856966 GG genotype (P = 0.0006, q = 0.17) and VIP CC haplotype (rs3823082-rs688136) (P = 0.0006) were suggestively associated with alcohol consumption in socially drinking controls. ARNTL2 GT haplotype (rs7958822-rs4964057) associated suggestively with alcohol abuse diagnosis (P = 0.0013). Earlier findings on the associations of DRD2 and NPY with alcohol dependence were supported: DRD2/ANKK1 Taq1A(1) increased (P = 0.04) and NPY Pro7 decreased (P = 0.01) the risk of alcohol dependence. Conclusions: ARNTL, ARNTL2, VIP and ADCYAP1 were indicated as having influence on alcohol use or abuse. The role of DRD2 and NPY on alcohol dependence was also supported.