Although, DNA methylation is an important regulator of gene transcription and altered DNA methylation may affect risk for many diseases, DNA methylation studies on AUDs are still at an early stage. Most DNA methylation studies on AUDs were published in the past 5 years. Compared to epigenetic studies on non-psychiatric diseases (eg, cancer), it is more challenging to study the epigenetic mechanisms of AUDs. This is because (i) AUDs are psychiatric conditions which have behavioral components plus a pharmacogenetic component and the direct pharmacological effects of alcohol. When comparing DNA methylome differences between AUD cases and controls, it is therefore, unknown whether epigenetic differences were already present before alcohol exposure (ie, are risk factors for AUDs) or whether they are consequent to chronic alcohol use; (ii) AUDs are highly comorbid with other substance use disorders and psychiatric illnesses, and thus, it is difficult to obtain a homogeneous sample (where subjects are diagnosed only with AUDs and there is no comorbidity) for AUD study; and perhaps most importantly; (iii) for epigenetic studies, we would prefer to study the most relevant tissue.
