Identification of two heritable cross-disorder endophenotypes for Tourette Syndrome
| Autor: | Cornelia Illmann, Dongmei Yu, Danielle C. Cath, Jeremiah M. Scharf, Robert A. King, Yves Dion, Carol A. Mathews, Marco Grados, William M. McMahon, Gholson J. Lyon, Cathy L. Budman, Paul C. Lee, Sabrina M. Darrow, Matthew E. Hirschtritt, Erica Greenberg, Kevin L. Delucchi, David L. Pauls, Lisa Osiecki, Paul Sandor, Lauren M. McGrath, Lea K. Davis |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male medicine.medical_specialty Multifactorial Inheritance Obsessive-Compulsive Disorder Adolescent Endophenotypes Mothers Comorbidity Tourette syndrome Risk Assessment Article 03 medical and health sciences Young Adult 0302 clinical medicine Child of Impaired Parents mental disorders medicine Attention deficit hyperactivity disorder Humans Genetic Predisposition to Disease Adhd symptoms Psychiatry Child Genetic heterogeneity Heritability Middle Aged medicine.disease 030227 psychiatry Psychiatry and Mental health Phenotype Attention Deficit Disorder with Hyperactivity Endophenotype Child Preschool Female Psychology 030217 neurology & neurosurgery Genome-Wide Association Study Tourette Syndrome |
| Popis: | Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses. |
| Databáze: | OpenAIRE |
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