GWAS identifies six genetic loci associated with Tourette syndrome in European ancestry populations.

This genome-wide association study (GWAS) investigated the genetic architecture of Tourette syndrome (TS) and tic disorders (TD). The analysis included 13,247 individuals with TD cases and 536,217 controls, all of European ancestry. The primary objective was to identify independent risk loci, while secondary analyses prioritized genes and examined associations with other traits.

The study identified six independent genome-wide significant loci. A pleiotropic signal was detected at 3p21, which is shared with attention-deficit/hyperactivity disorder. Gene prioritization highlighted 20 specific genes, including PCDH9, HCN1, NCKIPSD, WDR6, DALRD3, and CELSR3. Furthermore, integrative analyses linked genetic risk to dopamine D1- and D2-receptor-positive medium spiny neurons, cortical pyramidal neurons, and oligodendrocyte-lineage cells.

Extensive genetic correlations were observed with various neurodevelopmental and psychiatric traits. However, no significant genetic correlations were found with neurological disorders. The study did not report adverse events, discontinuations, or specific tolerability data, as these are not applicable to genetic association studies. Limitations include the restriction to European ancestry populations and the observational nature of GWAS data, which precludes causal inference.

While these results advance biological understanding of TS pathophysiology, they have limited immediate practice relevance for clinical management. The findings should be interpreted as identifying population-level genetic risk factors rather than diagnostic markers for individual patients. Clinicians should recognize these data as foundational for future research rather than current therapeutic guidance.