The long-term objective of this project is a better understanding of the role of genetic and environmental factors in human neuropsychiatric disorders through the study of the Gilles de la Tourette's syndrome (GTS), obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). Recent research has led to several notable advances in our understanding of GTS, OCD, ADHD and related conditions. This research suggests that: 1) there are components of GTS, OCD and ADHD that represent distinct heritable phenotypes; 2) there are susceptibility genes of major effect that contribute to the expression of GTS, OCD, ADHD and related conditions; 3) there are DMA markers in several genomic regions linked to susceptibility genes for each of these disorders; and 4) some of those genomic regions overlap, suggesting that some genes may be contributing to the susceptibility of shared components of each of these conditions. Furthermore, the prevalence of GTS, OCD, ADHD and associated illnesses and their debilitating affects on those afflicted makes these conditions a major public health problem. Understanding the genetic factors important for the manifestation of these conditions will be of direct benefit to patients concerned about recurrence in their families; ultimately, clarifying the genetics of these conditions may elucidate their pathogenesis and lead to more effective interventions. Results from our ongoing analyses suggest that there is an etiologic relationship between GTS, OCD and some types of ADHD. In this application, we are proposing to collect additional data that will make it possible to characterize more completely the nature of the relationship between GTS, OCD, ADHD and related conditions. We propose to collect data from 700 families of ascertained individuals with GTS, OCD and ADHD. This data will allow a more complete delineation of the components of each disorder and allow a more complete examination of the genetic relationship between GTS, OCD and ADHD and their component parts. Data from these new family study samples should help identify specific genetic factors associated with the variable expression of GTS, OCD and ADHD and related behaviors. In all cases, information will be obtained from all probands and family members by direct assessment of structured interviews, neurpsychological and neurocognitive tests.
| Abdulkadir, Mohamed; Mathews, Carol A; Scharf, Jeremiah M et al. (2018) Polygenic Risk Scores Derived From a Tourette Syndrome Genome-wide Association Study Predict Presence of Tics in the Avon Longitudinal Study of Parents and Children Cohort. Biol Psychiatry : |
| Darrow, Sabrina M; Grados, Marco; Sandor, Paul et al. (2017) Autism Spectrum Symptoms in a Tourette's Disorder Sample. J Am Acad Child Adolesc Psychiatry 56:610-617.e1 |
| Huang, Alden Y; Yu, Dongmei; Davis, Lea K et al. (2017) Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome. Neuron 94:1101-1111.e7 |
| Darrow, Sabrina M; Hirschtritt, Matthew E; Davis, Lea K et al. (2017) Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome. Am J Psychiatry 174:387-396 |
| Darrow, Sabrina M; Illmann, Cornelia; Gauvin, Caitlin et al. (2015) Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses. Psychiatry Res 228:816-25 |
| Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M et al. (2015) Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am J Psychiatry 172:82-93 |
| de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B et al. (2015) Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis. Eur J Hum Genet 23:1519-22 |
| Pauls, David L; Fernandez, Thomas V; Mathews, Carol A et al. (2014) The Inheritance of Tourette Disorder: A review. J Obsessive Compuls Relat Disord 3:380-385 |
| Paschou, Peristera; Yu, Dongmei; Gerber, Gloria et al. (2014) Genetic association signal near NTN4 in Tourette syndrome. Ann Neurol 76:310-5 |
| Pauls, David L; Abramovitch, Amitai; Rauch, Scott L et al. (2014) Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci 15:410-24 |
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