Proneness to infections and familial risk of tic disorders

Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders.

Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose-response associations using logistic regression models.

Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40-1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12-1.19) in cousins to 1.31 (1.25-1.37) in first-degree relatives. There was a dose-response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives.

Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.