Clock genes in human alcohol abuse and comorbid conditions.

Alcohol-use disorders are often comorbid conditions with mood and anxiety disorders. Clinical studies have demonstrated that there are abnormalities in circadian rhythms and clocks in patients with alcohol-use disorders. Circadian clock gene variants are therefore a fruitful target of interest. Concerning alcohol use, the current findings give support, but are preliminary to, the associations of ARNTL (BMAL1) rs6486120 with alcohol consumption, ARNTL2 rs7958822 and ARNTL2 rs4964057 with alcohol abuse, and PER1 rs3027172 and PER2 rs56013859 with alcohol dependence. Furthermore, it is of interest that CLOCK rs2412646 and CLOCK rs11240 associate with alcohol-use disorders only if comorbid with depressive disorders. The mechanistic basis of these associations and the intracellular actions for the encoded proteins in question remain to be elucidated in order to have the first insight of the potential small-molecule options for treatment of alcohol-use disorders.