Overall, PPAR agonists are beneficial for treating several key problems of AD: i) excessive consumption as demonstrated here and by previous studies (Barson et al., 2009; Stopponi et al., 2011; Stopponi et al., 2013), ii) ethanol-induced liver injury (Enomoto et al., 2003), iii) neurodegeneration (Mandrekar-Colucci et al., 2013), and iv) nicotine use (Mascia et al., 2011; Panlilio et al., 2012). We provide novel support for the efficacy of selective PPAR agonists in two mouse models of excessive alcohol consumption and found that human polymorphisms in specific PPAR genes may be associated with alcohol withdrawal or AD, demonstrating convergent evidence for PPARs in alcohol action in mice and humans. In particular, the evidence of association in humans is strongest for PPARGC1A and AD. Our proof of principle approach combines both mouse and human data to systematically evaluate and nominate specific PPARs. An overall similar approach recently showed that SNPs of FKBP5 were associated with alcohol withdrawal in humans, and Fkbp5 knockout mice also showed greater withdrawal severity (Huang et al., 2014). Our results provide support for the first human genetic link
