Familial Risks of Tourette Syndrome and Chronic Tic Disorders. A Population-Based Cohort Study
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...
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| Vydané v: | JAMA psychiatry (Chicago, Ill.) Ročník 72; číslo 8; s. 787 |
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| Hlavní autori: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
01.08.2015
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| ISSN: | 2168-6238, 2168-6238 |
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| Abstract | 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.
To provide unbiased estimates of familial risk and heritability of tic disorders at the population level.
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.
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.
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.
Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions. |
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| AbstractList | 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.
To provide unbiased estimates of familial risk and heritability of tic disorders at the population level.
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.
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.
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.
Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions. 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.IMPORTANCETic 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.To provide unbiased estimates of familial risk and heritability of tic disorders at the population level.OBJECTIVETo provide unbiased estimates of familial risk and heritability of tic disorders at the population level.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.DESIGN, SETTING, AND PARTICIPANTSIn 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.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.MAIN OUTCOMES AND MEASURESWe 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.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.RESULTSThe 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.Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions.CONCLUSIONS AND RELEVANCETic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions. |
| Author | Leckman, James F Isomura, Kayoko Rück, Christian Mataix-Cols, David Serlachius, Eva Larsson, Henrik Chang, Zheng Lichtenstein, Paul Pérez-Vigil, Ana Larsson, K Johan |
| Author_xml | – sequence: 1 givenname: David surname: Mataix-Cols fullname: Mataix-Cols, David organization: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden – sequence: 2 givenname: Kayoko surname: Isomura fullname: Isomura, Kayoko organization: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden – sequence: 3 givenname: Ana surname: Pérez-Vigil fullname: Pérez-Vigil, Ana organization: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden – sequence: 4 givenname: Zheng surname: Chang fullname: Chang, Zheng organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden – sequence: 5 givenname: Christian surname: Rück fullname: Rück, Christian organization: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden – sequence: 6 givenname: K Johan surname: Larsson fullname: Larsson, K Johan organization: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden – sequence: 7 givenname: James F surname: Leckman fullname: Leckman, James F organization: Child Study Center, Yale University, New Haven, Connecticut4Department of Psychiatry, Yale University, New Haven, Connecticut5Department of Pediatrics and Psychology, Yale University, New Haven, Connecticut – sequence: 8 givenname: Eva surname: Serlachius fullname: Serlachius, Eva organization: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden – sequence: 9 givenname: Henrik surname: Larsson fullname: Larsson, Henrik organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden – sequence: 10 givenname: Paul surname: Lichtenstein fullname: Lichtenstein, Paul organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden |
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| SubjectTerms | Child Cohort Studies Family - psychology Family Health - statistics & numerical data Female Genetic Predisposition to Disease Humans Male Models, Genetic Registries Risk Factors Sweden Tic Disorders - genetics Tourette Syndrome - genetics |
| Title | Familial Risks of Tourette Syndrome and Chronic Tic Disorders. A Population-Based Cohort Study |
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