Current treatments for tics and TD have limited efficacy and pharmacotherapies may carry significant long-term adverse effects. A fundamental obstacle to identifying novel therapeutic targets is a limited understanding of underlying pathophysiology. There is widespread agreement that genetics plays a significant role in TD etiology based on twin and family studies (Browne et al., 2015; Mataix-Cols et al., 2015; Pauls et al., 1981, 1991; Price et al., 1985). To date, non-parametric linkage analyses (The Tourette Syndrome Association International Consortium for Genetics, 1999, 2007) and a genome-wide association study (Scharf et al., 2013) have not yet led to reproducible, statistically significant findings. Studies of rare pedigrees have identified putative risk genes expressed in the developing striatum and mediating neurite outgrowth (Abelson et al., 2005; Stillman et al., 2009) or involved in histaminergic neurotransmission (Ercan-Sencicek et al., 2010), signal transduction and cell adhesion (Lawson-Yuen et al., 2008; Verkerk et al., 2003), or serotonin transport (Moya et al., 2013). None of these findings can yet be considered definitive.
