The Tourette Syndrome Association, IncThe Swedish Council for Working Life and Social ResearchThe Swedish Research CouncilManuscrip

Chang, Zheng

Isomura, Kayoko

Larsson, Henrik

Larsson, K. Johan

Leckman, James F.

Lichtenstein, Paul

Mataix-Cols, David

Pérez-Vigil, Ana

Rück, Christian

Serlachius, Eva

JAMA Psychiatry

Importance: Tic disorders, including Tourette syndrome (TS) and chronic tic disorders (CTDs), are assumed to be strongly familial and heritable. Although gene-searching efforts are well under way, 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 that contribute to the observed familiality. Twin studies have been either very small or based on parent-reported tics in population-based (nonclinical) twin samples.Objective: To provide unbiased estimates of familial risk and heritability of tic disorders at the population level.Design, setting, and participants: In this population cohort, multigenerational family study, we used a validated algorithm to identify 4826 individuals diagnosed as having TS or CTDs (76.2% male) in the Swedish National Patient Register from January 1, 1969, through December 31, 2009.Main outcomes and measures: We studied risks for TS or CTDs in all biological relatives of probands compared with relatives of unaffected individuals (matched on a 1:10 ratio) from the general population. Structural equation modeling was used to estimate the heritability of tic disorders.Results: The risk for tic disorders among relatives of probands with tic disorders increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives (odds ratio [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 (eg, parents, siblings, and offspring) had similar risks for tic disorders 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 those for maternal half siblings (25% genetic similarity; OR, 4.41; 95% CI, 2.24-8.67) despite similar environmental exposures. The heritability of tic disorders 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: Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions.</p

Mataix-Cols, David,

Isomura, Kayoko,

Pérez-Vigil, Ana,

Chang, Zheng,

Rück, Christian,

Larsson, K. Johan,

Leckman, James F.,

Serlachius, Eva,

Larsson, Henrik,

Lichtenstein, Paul,

Swepub

Familial Risks of Tourette Syndrome and Chronic Tic Disorders : A Population-Based Cohort Study

David Mataix-Cols

Kayoko Isomura

Ana Pérez-Vigil

Zheng Chang

Christian Rück

K. Johan Larsson

James F. Leckman

Eva Serlachius

Henrik Larsson

Paul Lichtenstein

Crossref

Familial Risks of Tourette Syndrome and Chronic Tic Disorders

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.Tourette Syndrome AssociationSwedish Council for Working Life and Social Research, 2012-1678Swedish Research Council, 2011-2492Accepte

Larsson, K Johan

Leckman, James F

Publications from Karolinska Institutet

Familial risks of Tourette syndrome and chronic tic disorders : a population-based cohort study

http://openarchive.ki.se/xmlui/bitstream/10616/45079/3/Mataix-Cols_2015.pdf

Familial Risks of Tourette Syndrome and Chronic Tic Disorders. A Population-Based Cohort Study.

Familial Risks of Tourette Syndrome and Chronic Tic Disorders. A Population-Based Cohort Study.

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