Abstract
Importance: Chronic Tic Disorders (CTD), including Tourette Syndrome (TS), are assumed to be strongly familial and heritable. While gene-searching efforts are well underway, precise estimates of familial risk and heritability are lacking. Previous controlled family studies were small and typically conducted within specialist clinics, resulting in potential ascertainment biases. They were also underpowered to disentangle genetic from environmental factors contributing to the observed familiality. Twin studies have been either very small or based on parent-reported tics in population-based (non-clinical) twin samples.
Objective: To provide unbiased estimates of familial risk and heritability of TS/CTD at the population level.
Design and Setting: Population cohort, multigenerational, family study.
Participants: Using a validated algorithm, we identified 4,826 individuals diagnosed with TS/CTD (76% male) in the Swedish National Patient Register between 1969-2009.
Main outcome measure: Risks (Odds Ratios; OR) for TS/CTD in all biological relatives of probands, compared to relatives of unaffected individuals (matched on a 1:10 ratio) from the general population. Structural equation modeling was used to estimate the heritability of TS/CTD.
Results: The risk for TS/CTD amongst relatives of TS/CTD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives (OR= 18.69, 95% CI 14.53-24.05) were significantly higher than for second-degree relatives (OR= 4.58, 95% CI 3.22-6.52) and third-degree relatives (OR= 3.07, 95% CI 2.08-4.51). First-degree relatives at similar genetic distances (e.g. parents, siblings, offspring) had similar risks for TS/CTD, despite different degrees of shared environment. The risks for full siblings (50% genetic similarity; OR=17.68, 95% CI 12.90-24.23) were significantly higher than that for maternal-half siblings (25% genetic similarity; OR= 4.41, 95% CI 2.24-8.67), despite similar environmental exposures. The heritability of TS/CTD was estimated to be 0.77 (95% CI 0.70-0.85). There were no differences in familial risk or heritability between male and female patients.
Conclusions and relevance: TS/CTD clusters in families primarily due to genetic factors and appears to be amongst the most heritable neuropsychiatric conditions.
