Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD
| Autor: | Mary M. Robertson, Peter Heutink, Leonhard Lennertz, Victor I. Reus, John Hardy, Mark A. Riddle, Beatriz Camarena, Helena Garrido, Robert A. King, Simon Girard, Christine Lochner, Michael H. Bloch, Patrick Evans, Anuar Konkashbaev, Jack Samuels, Priya Moorjani, Chiara Sabatti, Andrew J. Pakstis, Ying Wang, O. Joseph Bienvenu, Richard Delorme, David L. Pauls, Rainald Moessner, Gary A. Heiman, Daniel A. Geller, Marco A. Grados, Eric R. Gamazon, John Piacentini, Dan J. Stein, William Cornejo Ochoa, Maria Conceição do Rosário, Karin Egberts, Thomas L. Lowe, Christopher K. Edlund, Jan Smit, Christopher Pittenger, Denise A. Chavira, Marion Leboyer, Homero Vallada, Sandra Catalina Mesa Restrepo, Jacquelyn Crane, Donald W. Black, David V. Conti, Paul Sandor, Humberto Nicolini, Lisa Osiecki, Jeremy Veenstra-VanderWeele, Catherine Mayerfeld, Danielle Posthuma, Edna Grünblatt, Carolina Cappi, Robert B. Weiss, Cristina Barlassina, Sara Lupoli, Chunyu Liu, Sian M. J. Hemmings, Ben A. Oostra, D. Denys, Susanne Walitza, Lea K. Davis, Stephen A. Haddad, Luis Diego Herrera, Jubel Morgan, Hans Joergen Grabe, Benjamin M. Neale, Thomas V. Fernandez, Yehuda Pollak, Roel A. Ophoff, Gerald Nestadt, Harvey S. Singer, Stephan Ruhrmann, Bernadette Cullen, Michael Wagner, Nuria Lanzagorta, Jeremiah M. Scharf, Cathy L. Budman, Ruth D. Bruun, R. Kurlan, Valsama Eapen, Jesen Fagerness, Desmond Campbell, James L. Kennedy, Carlos N. Pato, Nancy J. Cox, Pieter J. Hoekstra, Joseph Jankovic, Cathy L. Barr, Peter Falkai, Donald L. Gilbert, Fortu Benarroch, Dianne M. Hezel, Maria Cristina Cavallini, Brooke Sheppard, Fabio Macciardi, William M. McMahon, Laura Bellodi, Maurizio Turiel, Wolfgang Maier, Varda Gross-Tsur, Helena Brentani, Dongmei Yu, Danielle C. Cath, Ana V. Valencia Duarte, Eduardo Fournier, James A. Knowles, Tobias J. Renner, Erika L. Nurmi, Guy A. Rouleau, Benjamin D. Greenberg, Nelson B. Freimer, Shaun Purcell, Patience J. Gallagher, Roxana Romero, Gregory L. Hanna, Paolo Manunta, Edwin H. Cook, Michele T. Pato, Sylvain Chouinard, Scott L. Rauch, James T. McCracken, Gloria Gerber, Carol A. Mathews, Jens R. Wendland, Sampath Arepalli, Dennis L. Murphy, Daniele Cusi, Barbara Kremeyer, Vladimir Coric, Aline S. Sampaio, Erika Salvi, Julio C. Cardona Silgado, Cornelia Illmann, James F. Leckman, Euripedes Constantino Miguel, H. Müller, Yin Yao Shugart, Eric Strengman, Ana Gabriela Hounie, Michael E. Weale, Gabriel Bedoya Berrió, Margaret A. Richter, Maurizio Marconi, Allan L. Naarden, Michael A. Jenike, M.R. Cookson, David R. Rosenberg, Andres Ruiz-Linares, S. Evelyn Stewart, Paul D. Arnold, H.G.M. Westenberg, Yves Dion, Jay A. Tischfield, Eske M. Derks, Lauren M. McGrath |
|---|---|
| Přispěvatelé: | Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Yu, D., Mathews, C. A., Scharf, J. M., Neale, B. M., Davis, L. K., Gamazon, E. R., Derks, E. M., Evans, P., Edlund, C. K., Crane, J., Fagerness, J. A., Osiecki, L., Gallagher, P., Gerber, G., Haddad, S., Illmann, C., Mcgrath, L. M., Mayerfeld, C., Arepalli, S., Barlassina, C., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Black, D., Bloch, M. H., Brentani, H., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D. D., Cappi, C., Cardona Silgado, J. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Cook, E. H., Cookson, M. R., Coric, V., Cullen, B., Cusi, D., Delorme, R., Denys, D., Dion, Y., Eapen, V., Egberts, K., Falkai, P., Fernandez, T., Fournier, E., Garrido, H., Geller, D., Gilbert, D., Girard, S. L., Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Grunblatt, E., Hardy, J., Heiman, G. A., Hemmings, S. M. J., Herrera, L. D., Hezel, D. M., Hoekstra, P. J., Jankovic, J., Kennedy, J. L., King, R. A., Konkashbaev, A. I., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Lupoli, S., Macciardi, F., Maier, W., Manunta, P., Marconi, M., Mccracken, J. T., Mesa Restrepo, S. C., Moessner, R., Moorjani, P., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Ruhrmann, S., Sabatti, C., Salvi, E., Sampaio, A. S., Samuels, J., Sandor, P., Service, S. K., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Turiel, M., Valencia Duarte, A. V., Vallada, H., Veenstra-VanderWeele, J., Walitza, S., Walkup, J., Wang, Y., Weale, M., Weiss, R., Wendland, J. R., Westenberg, H. G. M., Yao, Y., Hounie, A. G., Miguel, E. C., Nicolini, H., Wagner, M., Ruiz-Linares, A., Cath, D. C., Mcmahon, W., Posthuma, D., Oostra, B. A., Nestadt, G., Rouleau, G. A., Purcell, S., Jenike, M. A., Heutink, P., Hanna, G. L., Conti, D. V., Arnold, P. D., Freimer, N., Stewart, S. E., Knowles, J. A., Cox, N. J., Pauls, D. L., Netherlands Institute for Neuroscience (NIN), Sub String Theory Cosmology and ElemPart, Leerstoel Hout, Experimental psychopathology, Psychiatry, Human genetics, NCA - Neurobiology of mental health, EMGO - Mental health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Obsessive-Compulsive Disorder diagnosis [Tourette Syndrome] Tics Single-nucleotide polymorphism Genome-wide association study Comorbidity VARIANTS Tourette syndrome Polymorphism Single Nucleotide Severity of Illness Index ASSOCIATION SCANS 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Polymorphism (computer science) Severity of illness mental disorders medicine TICS Humans ddc:610 Polymorphism 030304 developmental biology Genetics Psychiatric Status Rating Scales genetics [Obsessive-Compulsive Disorder] 0303 health sciences GENERALIST GENES Single Nucleotide OBSESSIVE-COMPULSIVE DISORDER epidemiology [Tourette Syndrome] medicine.disease Genetic architecture Psychiatry and Mental health genetics [Tourette Syndrome] Female epidemiology [Obsessive-Compulsive Disorder] Psychology 030217 neurology & neurosurgery diagnosis [Obsessive-Compulsive Disorder] Genome-Wide Association Study Tourette Syndrome |
| Zdroj: | American Journal of Psychiatry, 172(1), 82-93. American Psychiatric Association The American Journal of Psychiatry, 172(1), 82-93. American Psychiatric Association The American journal of psychiatry 172(1), 82-93 (2015). doi:10.1176/appi.ajp.2014.13101306 Yu, D M, Mathews, C A, Scharf, J M, Neale, B M, Davis, L K, Gamazon, E R, Derks, E M, Evans, P, Edlund, C K, Crane, J, Osiecki, L, Gallagher, P, Gerber, G, Haddad, S, Illmann, C, McGrath, L M, Mayerfeld, C, Arepalli, S, Barlassina, C, Barr, C L, Bellodi, L, Benarroch, F, Berrio, G B, Bienvenu, O J, Black, D W, Bloch, M H, Brentani, H, Bruun, R D, Budman, C L, Camarena, B, Campbell, D D, Cappi, C, Silgado, J C C, Cavallini, M C, Chavira, D A, Chouinard, S, Cook, E H, Cookson, M R, Coric, V, Cullen, B, Cusi, D, Delorme, R, Denys, D, Dion, Y, Eapen, V, Egberts, K, Falkai, P, Fernandez, T, Fournier, E, Garrido, H, Geller, D, Gilbert, D L, Girard, S L, Grabe, H J, Grados, M A, Greenberg, B D, Gross-Tsur, V, Grunblatt, E, Hardy, J, Heiman, G A, Hemmings, S M J, Herrera, L D, Hezel, D M, Hoekstra, P J, Jankovic, J, Kennedy, J L, King, R A, Konkashbaev, A I, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, J F, Lennertz, L, Liu, C Y, Lochner, C, Lowe, T L, Lupoli, S, Macciardi, F, Maier, W, Manunta, P, Marconi, M, McCracken, J T, Restrepo, S C M, Moessner, R, Moorjani, P, Morgan, J, Muller, H, Murphy, D L, Naarden, A L, Nurmi, E, Ochoa, W C, Ophoff, R A, Pakstis, A J, Pato, M T, Pato, C N, Piacentini, J, Pittenger, C, Pollak, Y, Smit, J H, Posthuma, D, Cox, N J & Pauls, D L 2015, ' Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD ', American Journal of Psychiatry, vol. 172, no. 1, pp. 82-93 . https://doi.org/10.1176/appi.ajp.2014.13101306 American Journal of Psychiatry, 172(1), 82-93. AMER PSYCHIATRIC PUBLISHING, INC American Journal of Psychiatry, 172(1), 82. American Psychiatric Association American journal of psychiatry, 172(1), 82-93. American Psychiatric Association |
| ISSN: | 0002-953X |
| Popis: | Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|