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1. Clinical utility of MRI in the neoadjuvant management of early-stage breast cancer

Author: Corke, L., Luzhna, L., Willemsma, K., Illmann, C., Mcdermott, M., Wilson, C., Simmons, C., and LeVasseur, N.
Published: 2022
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2. Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

Author: Hirschtritt, ME, Darrow, SM, Illmann, C, Osiecki, L, Grados, M, Sandor, P, Dion, Y, King, RA, Pauls, D, Budman, CL, Cath, DC, Greenberg, E, Lyon, GJ, Yu, D, McGrath, LM, McMahon, WM, Lee, PC, Delucchi, KL, Scharf, JM, and Mathews, CA
Subjects: Humans, Tourette Syndrome, Family, Obsessive-Compulsive Disorder, Attention Deficit Disorder with Hyperactivity, Phenotype, Attention-deficit/hyperactivity disorder, Tourette syndrome, factors, heritability, latent classes, obsessive-compulsive disorder, Anxiety Disorders, Mental Health, Behavioral and Social Science, Pediatric, Neurosciences, Serious Mental Illness, Brain Disorders, Neurodegenerative, Attention Deficit Hyperactivity Disorder (ADHD), Mental health, Public Health and Health Services, Psychology, Psychiatry
Abstract: BackgroundThe unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.MethodOCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.ResultsEFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).ConclusionsSymmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.
Published: 2018

3. Genome-wide association study of Tourettes syndrome.

Author: Neale, B, Stewart, S, Fagerness, J, Evans, P, Gamazon, E, Edlund, C, Service, S, Tikhomirov, A, Osiecki, L, Illmann, C, Pluzhnikov, A, Konkashbaev, A, Davis, L, Han, B, Crane, J, Scharf, J, Yu, D, Rangel-Lugo, M, Chouinard, S, Dion, Y, Girard, S, Cath, D, Smit, J, King, R, Fernandez, T, Leckman, J, Kidd, K, Kidd, J, Pakstis, A, Herrera, L, Romero, R, Fournier, E, Sandor, P, Barr, C, Phan, N, Gross-Tsur, V, Benarroch, F, Pollak, Y, Budman, C, Bruun, R, Erenberg, G, Naarden, A, Lee, P, Weiss, N, Kremeyer, B, Berrío, G, Campbell, D, Cardona Silgado, J, Ochoa, W, Mesa Restrepo, S, Muller, H, Valencia Duarte, A, Lyon, G, Leppert, M, Morgan, J, Weiss, R, Grados, M, Anderson, K, Davarya, S, Singer, H, Walkup, J, Jankovic, J, Tischfield, J, Heiman, G, Gilbert, D, Hoekstra, P, Robertson, M, Kurlan, R, Liu, C, Gibbs, J, Singleton, A, Hardy, J, Strengman, E, Crenshaw, A, Parkin, M, Wagner, M, Moessner, R, Mirel, D, Posthuma, D, Sabatti, C, Conti, D, Knowles, J, Ruiz-Linares, A, Rouleau, G, Purcell, S, Heutink, P, Oostra, B, McMahon, W, Cox, N, Pauls, D, Reus, Victor, State, Matthew, Eskin, Eleazar, Mathews, Carol, Lowe, Thomas, Freimer, Nelson, Ophoff, Roel, and Moorjani, Priya
Subjects: Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Chromosomes, Human, Pair 9, Female, Fibrillar Collagens, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, International Cooperation, Male, Meta-Analysis as Topic, Obsessive-Compulsive Disorder, Polymorphism, Single Nucleotide, Tourette Syndrome, White People, Young Adult
Abstract: Tourettes syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P
Published: 2013

4. Genome-wide association study of Tourette's syndrome.

Author: Scharf, JM, Yu, D, Mathews, CA, Neale, BM, Stewart, SE, Fagerness, JA, Evans, P, Gamazon, E, Edlund, CK, Service, SK, Tikhomirov, A, Osiecki, L, Illmann, C, Pluzhnikov, A, Konkashbaev, A, Davis, LK, Han, B, Crane, J, Moorjani, P, Crenshaw, AT, Parkin, MA, Reus, VI, Lowe, TL, Rangel-Lugo, M, Chouinard, S, Dion, Y, Girard, S, Cath, DC, Smit, JH, King, RA, Fernandez, TV, Leckman, JF, Kidd, KK, Kidd, JR, Pakstis, AJ, State, MW, Herrera, LD, Romero, R, Fournier, E, Sandor, P, Barr, CL, Phan, N, Gross-Tsur, V, Benarroch, F, Pollak, Y, Budman, CL, Bruun, RD, Erenberg, G, Naarden, AL, Lee, PC, Weiss, N, Kremeyer, B, Berrío, GB, Campbell, DD, Cardona Silgado, JC, Ochoa, WC, Mesa Restrepo, SC, Muller, H, Valencia Duarte, AV, Lyon, GJ, Leppert, M, Morgan, J, Weiss, R, Grados, MA, Anderson, K, Davarya, S, Singer, H, Walkup, J, Jankovic, J, Tischfield, JA, Heiman, GA, Gilbert, DL, Hoekstra, PJ, Robertson, MM, Kurlan, R, Liu, C, Gibbs, JR, Singleton, A, North American Brain Expression Consortium, Hardy, J, UK Human Brain Expression Database, Strengman, E, Ophoff, RA, Wagner, M, Moessner, R, Mirel, DB, Posthuma, D, Sabatti, C, Eskin, E, Conti, DV, Knowles, JA, Ruiz-Linares, A, Rouleau, GA, Purcell, S, Heutink, P, Oostra, BA, McMahon, WM, Freimer, NB, Cox, NJ, and Pauls, DL
Subjects: North American Brain Expression Consortium, UK Human Brain Expression Database, Chromosomes, Human, Pair 9, Humans, Tourette Syndrome, Genetic Predisposition to Disease, Fibrillar Collagens, Case-Control Studies, Obsessive-Compulsive Disorder, Attention Deficit Disorder with Hyperactivity, Genotype, Polymorphism, Single Nucleotide, International Cooperation, Adolescent, Adult, Female, Male, Meta-Analysis as Topic, Genome-Wide Association Study, Young Adult, White People, Genetics, Human Genome, Mental Health, Brain Disorders, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, genetics, GWAS, neurodevelopmental disorder, tics, Tourette's syndrome, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P
Published: 2013

5. Impact of Recurrence Score on Type and Duration of Chemotherapy in Breast Cancer

Author: Willemsma, K., primary, Yip, W., additional, LeVasseur, N., additional, Dobosz, K., additional, Illmann, C., additional, Baxter, S., additional, Lohrisch, C., additional, and Simmons, C.E., additional
Published: 2020
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6. Analysis of shared heritability in common disorders of the brain

Author: Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe, P. Depondt, C. Dlugos, D. Ferraro, T.N. French, J. Hjalgrim, H. Jamnadas-Khoda, J. Kälviäinen, R. Kunz, W.S. Lerche, H. Leu, C. Lindhout, D. Lo, W. Lowenstein, D. McCormack, M. Møller, R.S. Molloy, A. Ng, P.-W. Oliver, K. Privitera, M. Radtke, R. Ruppert, A.-K. Sander, T. Schachter, S. Schankin, C. Scheffer, I. Schoch, S. Sisodiya, S.M. Smith, P. Sperling, M. Striano, P. Surges, R. Neil Thomas, G. Visscher, F. Whelan, C.D. Zara, F. Heinzen, E.L. Marson, A. Becker, F. Stroink, H. Zimprich, F. Gasser, T. Gibbs, R. Heutink, P. Martinez, M. Morris, H.R. Sharma, M. Ryten, M. Mok, K.Y. Pulit, S. Bevan, S. Holliday, E. Attia, J. Battey, T. Boncoraglio, G. Thijs, V. Chen, W.-M. Mitchell, B. Rothwell, P. Sharma, P. Sudlow, C. Vicente, A. Markus, H. Kourkoulis, C. Pera, J. Raffeld, M. Silliman, S. Perica, V.B. Thornton, L.M. Huckins, L.M. William Rayner, N. Lewis, C.M. Gratacos, M. Rybakowski, F. Keski-Rahkonen, A. Raevuori, A. Hudson, J.I. Reichborn-Kjennerud, T. Monteleone, P. Karwautz, A. Mannik, K. Baker, J.H. O'Toole, J.K. Trace, S.E. Davis, O.S.P. Helder, S.G. Ehrlich, S. Herpertz-Dahlmann, B. Danner, U.N. Van Elburg, A.A. Clementi, M. Forzan, M. Docampo, E. Lissowska, J. Hauser, J. Tortorella, A. Maj, M. Gonidakis, F. Tziouvas, K. Papezova, H. Yilmaz, Z. Wagner, G. Cohen-Woods, S. Herms, S. Julia, A. Rabionet, R. Dick, D.M. Ripatti, S. Andreassen, O.A. Espeseth, T. Lundervold, A.J. Steen, V.M. Pinto, D. Scherer, S.W. Aschauer, H. Schosser, A. Alfredsson, L. Padyukov, L. Halmi, K.A. Mitchell, J. Strober, M. Bergen, A.W. Kaye, W. Szatkiewicz, J.P. Cormand, B. Ramos-Quiroga, J.A. Sánchez-Mora, C. Ribasés, M. Casas, M. Hervas, A. Arranz, M.J. Haavik, J. Zayats, T. Johansson, S. Williams, N. Dempfle, A. Rothenberger, A. Kuntsi, J. Oades, R.D. Banaschewski, T. Franke, B. Buitelaar, J.K. Vasquez, A.A. Doyle, A.E. Reif, A. Lesch, K.-P. Freitag, C. Rivero, O. Palmason, H. Romanos, M. Langley, K. Rietschel, M. Witt, S.H. Dalsgaard, S. Børglum, A.D. Waldman, I. Wilmot, B. Molly, N. Bau, C.H.D. Crosbie, J. Schachar, R. Loo, S.K. McGough, J.J. Grevet, E.H. Medland, S.E. Robinson, E. Weiss, L.A. Bacchelli, E. Bailey, A. Bal, V. Battaglia, A. Betancur, C. Bolton, P. Cantor, R. Celestino-Soper, P. Dawson, G. De Rubeis, S. Duque, F. Green, A. Klauck, S.M. Leboyer, M. Levitt, P. Maestrini, E. Mane, S. Moreno-De-Luca, D. Parr, J. Regan, R. Reichenberg, A. Sandin, S. Vorstman, J. Wassink, T. Wijsman, E. Cook, E. Santangelo, S. Delorme, R. Roge, B. Magalhaes, T. Arking, D. Schulze, T.G. Thompson, R.C. Strohmaier, J. Matthews, K. Melle, I. Morris, D. Blackwood, D. McIntosh, A. Bergen, S.E. Schalling, M. Jamain, S. Maaser, A. Fischer, S.B. Reinbold, C.S. Fullerton, J.M. Guzman-Parra, J. Mayoral, F. Schofield, P.R. Cichon, S. Mühleisen, T.W. Degenhardt, F. Schumacher, J. Bauer, M. Mitchell, P.B. Gershon, E.S. Rice, J. Potash, J.B. Zandi, P.P. Craddock, N. Nicol Ferrier, I. Alda, M. Rouleau, G.A. Turecki, G. Ophoff, R. Pato, C. Anjorin, A. Stahl, E. Leber, M. Czerski, P.M. Cruceanu, C. Jones, I.R. Posthuma, D. Andlauer, T.F.M. Forstner, A.J. Streit, F. Baune, B.T. Air, T. Sinnamon, G. Wray, N.R. MacIntyre, D.J. Porteous, D. Homuth, G. Rivera, M. Grove, J. Middeldorp, C.M. Hickie, I. Pergadia, M. Mehta, D. Smit, J.H. Jansen, R. De Geus, E. Dunn, E. Li, Q.S. Nauck, M. Schoevers, R.A. Beekman, A.T.F. Knowles, J.A. Viktorin, A. Arnold, P. Barr, C.L. Bedoya-Berrio, G. Joseph Bienvenu, O. Brentani, H. Burton, C. Camarena, B. Cappi, C. Cath, D. Cavallini, M. Cusi, D. Darrow, S. Denys, D. Derks, E.M. Dietrich, A. Fernandez, T. Figee, M. Freimer, N. Gerber, G. Grados, M. Greenberg, E. Hanna, G.L. Hartmann, A. Hirschtritt, M.E. Hoekstra, P.J. Huang, A. Huyser, C. Illmann, C. Jenike, M. Kuperman, S. Leventhal, B. Lochner, C. Lyon, G.J. Macciardi, F. Madruga-Garrido, M. Malaty, I.A. Maras, A. McGrath, L. Miguel, E.C. Mir, P. Nestadt, G. Nicolini, H. Okun, M.S. Pakstis, A. Paschou, P. Piacentini, J. Pittenger, C. Plessen, K. Ramensky, V. Ramos, E.M. Reus, V. Richter, M.A. Riddle, M.A. Robertson, M.M. Roessner, V. Rosário, M. Samuels, J.F. Sandor, P. Stein, D.J. Tsetsos, F. Van Nieuwerburgh, F. Weatherall, S. Wendland, J.R. Wolanczyk, T. Worbe, Y. Zai, G. Goes, F.S. McLaughlin, N. Nestadt, P.S. Grabe, H.-J. Depienne, C. Konkashbaev, A. Lanzagorta, N. Valencia-Duarte, A. Bramon, E. Buccola, N. Cahn, W. Cairns, M. Chong, S.A. Cohen, D. Crespo-Facorro, B. Crowley, J. Davidson, M. DeLisi, L. Dinan, T. Donohoe, G. Drapeau, E. Duan, J. Haan, L. Hougaard, D. Karachanak-Yankova, S. Khrunin, A. Klovins, J. Kučinskas, V. Keong, J.L.C. Limborska, S. Loughland, C. Lönnqvist, J. Maher, B. Mattheisen, M. McDonald, C. Murphy, K.C. Nenadic, I. Van Os, J. Pantelis, C. Pato, M. Petryshen, T. Quested, D. Roussos, P. Sanders, A.R. Schall, U. Schwab, S.G. Sim, K. So, H.-C. Stögmann, E. Subramaniam, M. Toncheva, D. Waddington, J. Walters, J. Weiser, M. Cheng, W. Cloninger, R. Curtis, D. Gejman, P.V. Henskens, F. Mattingsdal, M. Oh, S.-Y. Scott, R. Webb, B. Breen, G. Churchhouse, C. Bulik, C.M. Daly, M. Dichgans, M. Faraone, S.V. Guerreiro, R. Holmans, P. Kendler, K.S. Koeleman, B. Mathews, C.A. Price, A. Scharf, J. Sklar, P. Williams, J. Wood, N.W. Cotsapas, C. Palotie, A. Smoller, J.W. Sullivan, P. Rosand, J. Corvin, A. Neale, B.M. The Brainstorm Consortium
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.
Published: 2018

7. Analysis of shared heritability in common disorders of the brain

Author: Anttila, V, Bulik-Sullivan, B, Finucane, H, Walters, R, Bras, J, Duncan, L, Escott-Price, V, Falcone, G, Gormley, P, Malik, R, Patsopoulos, N, Ripke, S, Wei, Z, Yu, D, Lee, P, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J, Duron, E, Vardarajan, B, Reitz, C, Goate, A, Huentelman, M, Ilyas Kamboh, M, Larson, E, Rogaeva, E, George-Hyslop, P, Hakonarson, H, Kukull, W, Farrer, L, Barnes, L, Beach, T, Yesim Demirci, F, Head, E, Hulette, C, Jicha, G, Kauwe, J, Kaye, J, Leverenz, J, Levey, A, Lieberman, A, Pankratz, V, Poon, W, Quinn, J, Saykin, A, Schneider, L, Smith, A, Sonnen, J, Stern, R, Van Deerlin, V, Van Eldik, L, Harold, D, Russo, G, Rubinsztein, D, Bayer, A, Tsolaki, M, Proitsi, P, Fox, N, Hampel, H, Owen, M, Mead, S, Passmore, P, Morgan, K, Nöthen, M, Rossor, M, Lupton, M, Hoffmann, P, Kornhuber, J, Lawlor, B, Mcquillin, A, Al-Chalabi, A, Bis, J, Ruiz, A, Boada, M, Seshadri, S, Beiser, A, Rice, K, Van Der Lee, S, De Jager, P, Geschwind, D, Riemenschneider, M, Riedel-Heller, S, Rotter, J, Ransmayr, G, Hyman, B, Cruchaga, C, Alegret, M, Winsvold, B, Palta, P, Farh, K, Cuenca-Leon, E, Furlotte, N, Kurth, T, Ligthart, L, Terwindt, G, Freilinger, T, Ran, C, Gordon, S, Borck, G, Adams, H, Lehtimäki, T, Wedenoja, J, Buring, J, Schürks, M, Hrafnsdottir, M, Hottenga, J, Penninx, B, Artto, V, Kaunisto, M, Vepsäläinen, S, Martin, N, Montgomery, G, Kurki, M, Hämäläinen, E, Huang, H, Huang, J, Sandor, C, Webber, C, Muller-Myhsok, B, Schreiber, S, Salomaa, V, Loehrer, E, Göbel, H, Macaya, A, Pozo-Rosich, P, Hansen, T, Werge, T, Kaprio, J, Metspalu, A, Kubisch, C, Ferrari, M, Belin, A, Van Den Maagdenberg, A, Zwart, J, Boomsma, D, Eriksson, N, Olesen, J, Chasman, D, Nyholt, D, Avbersek, A, Baum, L, Berkovic, S, Bradfield, J, Buono, R, Catarino, C, Cossette, P, De Jonghe, P, Depondt, C, Dlugos, D, Ferraro, T, French, J, Hjalgrim, H, Jamnadas-Khoda, J, Kälviäinen, R, Kunz, W, Lerche, H, Leu, C, Lindhout, D, Lo, W, Lowenstein, D, Mccormack, M, Møller, R, Molloy, A, Ng, P, Oliver, K, Privitera, M, Radtke, R, Ruppert, A, Sander, T, Schachter, S, Schankin, C, Scheffer, I, Schoch, S, Sisodiya, S, Smith, P, Sperling, M, Striano, P, Surges, R, Neil Thomas, G, Visscher, F, Whelan, C, Zara, F, Heinzen, E, Marson, A, Becker, F, Stroink, H, Zimprich, F, Gasser, T, Gibbs, R, Heutink, P, Martinez, M, Morris, H, Sharma, M, Ryten, M, Mok, K, Pulit, S, Bevan, S, Holliday, E, Attia, J, Battey, T, Boncoraglio, G, Thijs, V, Chen, W, Mitchell, B, Rothwell, P, Sharma, P, Sudlow, C, Vicente, A, Markus, H, Kourkoulis, C, Pera, J, Raffeld, M, Silliman, S, Perica, V, Thornton, L, Huckins, L, William Rayner, N, Lewis, C, Gratacos, M, Rybakowski, F, Keski-Rahkonen, A, Raevuori, A, Hudson, J, Reichborn-Kjennerud, T, Monteleone, P, Karwautz, A, Mannik, K, Baker, J, O'Toole, J, Trace, S, Davis, O, Helder, S, Ehrlich, S, Herpertz-Dahlmann, B, Danner, U, Van Elburg, A, Clementi, M, Forzan, M, Docampo, E, Lissowska, J, Hauser, J, Tortorella, A, Maj, M, Gonidakis, F, Tziouvas, K, Papezova, H, Yilmaz, Z, Wagner, G, Cohen-Woods, S, Herms, S, Julia, A, Rabionet, R, Dick, D, Ripatti, S, Andreassen, O, Espeseth, T, Lundervold, A, Steen, V, Pinto, D, Scherer, S, Aschauer, H, Schosser, A, Alfredsson, L, Padyukov, L, Halmi, K, Mitchell, J, Strober, M, Bergen, A, Kaye, W, Szatkiewicz, J, Cormand, B, Ramos-Quiroga, J, Sánchez-Mora, C, Ribasés, M, Casas, M, Hervas, A, Arranz, M, Haavik, J, Zayats, T, Johansson, S, Williams, N, Dempfle, A, Rothenberger, A, Kuntsi, J, Oades, R, Banaschewski, T, Franke, B, Buitelaar, J, Vasquez, A, Doyle, A, Reif, A, Lesch, K, Freitag, C, Rivero, O, Palmason, H, Romanos, M, Langley, K, Rietschel, M, Witt, S, Dalsgaard, S, Børglum, A, Waldman, I, Wilmot, B, Molly, N, Bau, C, Crosbie, J, Schachar, R, Loo, S, Mcgough, J, Grevet, E, Medland, S, Robinson, E, Weiss, L, Bacchelli, E, Bailey, A, Bal, V, Battaglia, A, Betancur, C, Bolton, P, Cantor, R, Celestino-Soper, P, Dawson, G, De Rubeis, S, Duque, F, Green, A, Klauck, S, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, Moreno-De-Luca, D, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Roge, B, Magalhaes, T, Arking, D, Schulze, T, Thompson, R, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, Mcintosh, A, Bergen, S, Schalling, M, Jamain, S, Maaser, A, Fischer, S, Reinbold, C, Fullerton, J, Guzman-Parra, J, Mayoral, F, Schofield, P, Cichon, S, Mühleisen, T, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, P, Gershon, E, Rice, J, Potash, J, Zandi, P, Craddock, N, Nicol Ferrier, I, Alda, M, Rouleau, G, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, P, Cruceanu, C, Jones, I, Posthuma, D, Andlauer, T, Forstner, A, Streit, F, Baune, B, Air, T, Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, J, Wolanczyk, T, Worbe, Y, Zai, G, Goes, F, Mclaughlin, N, Nestadt, P, Grabe, H, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Anttila, Verneri, Bulik-Sullivan, Brendan, 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M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Neil Thomas, G., Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, BONCORAGLIO, GIORGIO BATTISTA, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., William Rayner, N., Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., Van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A., Mitchell, James, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K., Vasquez, Alejandro Arias, Doyle, Alysa E., Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Børglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton H. D., Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K., McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B., Reinbold, Céline S., Fullerton, Janice M., Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Mühleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Nicol Ferrier, I., Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F. M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthias, Schoevers, Robert A., Beekman, Aartjan TF, Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Joseph Bienvenu, O., Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andreas, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A., Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosário, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M., Anttila, V, Bulik-Sullivan, B, Finucane, H, Walters, R, Bras, J, Duncan, L, Escott-Price, V, Falcone, G, Gormley, P, Malik, R, Patsopoulos, N, Ripke, S, Wei, Z, Yu, D, Lee, P, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J, Duron, E, Vardarajan, B, Reitz, C, Goate, A, Huentelman, M, Ilyas Kamboh, M, Larson, E, Rogaeva, E, George-Hyslop, P, Hakonarson, H, Kukull, W, Farrer, L, Barnes, L, Beach, T, Yesim Demirci, F, Head, E, Hulette, C, Jicha, G, Kauwe, J, Kaye, J, Leverenz, J, Levey, A, Lieberman, A, Pankratz, V, Poon, W, Quinn, J, Saykin, A, Schneider, L, Smith, A, Sonnen, J, Stern, R, Van Deerlin, V, Van Eldik, L, Harold, D, Russo, G, Rubinsztein, D, Bayer, A, Tsolaki, M, Proitsi, P, Fox, N, Hampel, H, Owen, M, Mead, S, Passmore, P, Morgan, K, Nöthen, M, Rossor, M, Lupton, M, Hoffmann, P, Kornhuber, J, Lawlor, B, Mcquillin, A, Al-Chalabi, A, Bis, J, Ruiz, A, Boada, M, Seshadri, S, Beiser, A, Rice, K, Van Der Lee, S, De Jager, P, Geschwind, D, Riemenschneider, M, Riedel-Heller, S, Rotter, J, Ransmayr, G, Hyman, B, Cruchaga, C, Alegret, M, Winsvold, B, Palta, P, Farh, K, Cuenca-Leon, E, Furlotte, N, Kurth, T, Ligthart, L, Terwindt, G, Freilinger, T, Ran, C, Gordon, S, Borck, G, Adams, H, Lehtimäki, T, Wedenoja, J, Buring, J, Schürks, M, Hrafnsdottir, M, Hottenga, J, Penninx, B, Artto, V, Kaunisto, M, Vepsäläinen, S, Martin, N, Montgomery, G, Kurki, M, Hämäläinen, E, Huang, H, Huang, J, Sandor, C, Webber, C, Muller-Myhsok, B, Schreiber, S, Salomaa, V, Loehrer, E, Göbel, H, Macaya, A, Pozo-Rosich, P, Hansen, T, Werge, T, Kaprio, J, Metspalu, A, Kubisch, C, Ferrari, M, Belin, A, Van Den Maagdenberg, A, Zwart, J, Boomsma, D, Eriksson, N, Olesen, J, Chasman, D, Nyholt, D, Avbersek, A, Baum, L, Berkovic, S, Bradfield, J, Buono, R, Catarino, C, 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H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. J. M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Neil Thomas, G., Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, BONCORAGLIO, GIORGIO BATTISTA, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., William Rayner, N., Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., Van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A., Mitchell, James, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K., Vasquez, Alejandro Arias, Doyle, Alysa E., Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Børglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton H. D., Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K., McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B., Reinbold, Céline S., Fullerton, Janice M., Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Mühleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Nicol Ferrier, I., Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F. M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthias, Schoevers, Robert A., Beekman, Aartjan TF, Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Joseph Bienvenu, O., Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andreas, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A., Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosário, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, and Neale, Benjamin M.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
Published: 2018

8. Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome

Author: Hirschtritt, M. E., primary, Darrow, S. M., additional, Illmann, C., additional, Osiecki, L., additional, Grados, M., additional, Sandor, P., additional, Dion, Y., additional, King, R. A., additional, Pauls, D., additional, Budman, C. L., additional, Cath, D. C., additional, Greenberg, E., additional, Lyon, G. J., additional, Yu, D., additional, McGrath, L. M., additional, McMahon, W. M., additional, Lee, P. C., additional, Delucchi, K. L., additional, Scharf, J. M., additional, and Mathews, C. A., additional
Published: 2017
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9. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome

Author: Hirschtritt, ME, Lee, PC, Pauls, DL, Dion, Y, Grados, MA, Illmann, C, King, RA, Sandor, P, McMahon, WM, Lyon, GJ, Cath, DC, Kurlan, R, Robertson, MM, Osiecki, L, Scharf, JM, Mathews, CA, Posthuma, D, Singer, HS, Yu, D, Cox, NJ, Freimer, NB, Budman, CL, Chouinard, S, Rouleau, GA, Barr, CL, Complex Trait Genetics, and Neuroscience Campus Amsterdam - Neurobiology of Mental Health
Subjects: Male, medicine.medical_specialty, Tic disorder, Canada, Adolescent, for the Tourette Syndrome Association International Consortium for Genetics, Comorbidity, Tourette syndrome, behavioral disciplines and activities, Young Adult, Age Distribution, SDG 3 - Good Health and Well-being, Risk Factors, mental disorders, medicine, Prevalence, Attention deficit hyperactivity disorder, Humans, Age of Onset, Psychiatry, Preschool, Child, Netherlands, Mental Disorders, Age Factors, Great Britain, medicine.disease, United States, 3. Good health, Psychiatry and Mental health, Mood disorders, Child, Preschool, Anxiety, Female, Mental disorders diagnosed in childhood, medicine.symptom, Psychology, Anxiety disorder, Clinical psychology, Tourette Syndrome
Abstract: © 2015 American Medical Association. All rights reserved. Importance: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, fewstudies have fully characterized these comorbidities. Furthermore, most studies have included relatively fewparticipants (< 200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS.Objective: To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS.Design, Setting, And Participants: Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142).Main Outcomes And Measures: Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history.Results: The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7%of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95%CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95%CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%)may be accounted for by comorbid OCD (OR, 3.7; 95%CI, 2.9-4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95%CI, 1.32-2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD.Conclusions And Relevance: This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbiditiesmay be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbiditiesmay be more biologically related to OCD and/or ADHD rather than to TS.
Published: 2015
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10. Abstract P3-02-09: Do radiographic features influence the decision to order a breast MRI? A prospective cohort study

Author: Illmann, C, primary, Simmons, CE, additional, McDermott, M, additional, Xu, J, additional, and Wilson, C, additional
Published: 2017
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11. Abstract P3-02-05: Does MRI influence surgical planning more than clinical outcome? A cohort study of breast cancer patients receiving neoadjuvant therapy

Author: McDermott, M, primary, Wilson, C, additional, Xu, J, additional, Illmann, C, additional, and Simmons, C, additional
Published: 2017
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12. Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

Author: McGrath, L.M., Yu, D. (D.), Marshall, C.R. (Christian), Davis, L.K. (Lea), Thiruvahindrapuram, B. (Bhooma), Li, B. (Bingbin), Cappi, C. (Carolina), Gerber, G. (Gloria), Wolf, A. (Anneke) de, Schroeder, F.A. (Frederick), Osiecki, L. (Lisa), O'Dushlaine, C. (Colm), Kirby, A. (Andrew), Illmann, C. (Cornelia), Haddad, S. (Stephen), Gallagher, P. (Patience), Fagerness, J. (Jesen), Barr, C.L. (Cathy), Bellodi, L. (Laura), Benarroch, F. (Fortu), Bienvenu, O.J. (Oscar), Black, D.W. (Donald), Bloch, J. (Jocelyne), Bruun, R.D. (Ruth), Budman, C.L. (Cathy), Camarena, B. (Beatriz), Cath, D. (Daniëlle), Cavallini, M.C. (Maria), Chouinard, S., Coric, V. (Vladimir), Cullen, C., Delorme, R. (Richard), Denys, D.A.J.P. (Damiaan), Derks, E.M. (Eske), Dion, Y. (Yves), Rosário, M.C. (Maria), Eapen, C.E. (Chundamannil Eapen), Evans, P., Falkai, P. (Peter), Fernandez, T.V. (Thomas), Garrido, H. (Helena), Geller, D. (Daniel), Grabe, H.J. (Hans Jörgen), Grados, M. (Marco), Greenberg, B.D. (Benjamin), Gross-Tsur, V. (Varda), Grünblatt, E. (Edna), Heiman, M.L. (Mark), Hemmings, S.M.J. (Sian), Herrera, L.D. (Luis), Hounie, A.G. (Ana), Jankovic, J. (Joseph), Kennedy, J.L., King, R.A., Kurlan, R., Lanzagorta, N. (Nuria), Leboyer, M. (Marion), Leckman, J.F., Lennertz, L. (Leonhard), Lochner, C. (Christine), Lowe, T.L. (Thomas), Lyon, H.N. (Helen), MacCiardi, F. (Fabio), Maier, W. (Wolfgang), McCracken, J.T. (James), McMahon, W.M. (William), Murphy, D.L. (Dennis), Naarden, A.L. (Allan), Nurmi, E. (Erika), Pakstis, A.J., Pato, C. (Carlos), Piacentini, J. (John), Pittenger, C. (Christopher), Pollak, M.N. (Michael), Reus, V.I. (Victor), Richter, M.A. (Margaret), Riddle, M. (Mark), Robertson, M.M., Rosenberg, D. (David), Rouleau, G.A., Ruhrmann, S. (Stephan), Sampaio, A.S. (Aline), Samuels, J. (Jonathan), Sandor, P. (Paul), Sheppard, B. (Brooke), Singer, H.S. (Harvey), Smit, J.H. (Jan), Stein, D.J. (Dan), Tischfield, J.A. (Jay), Vallada, H. (Homero), Veenstra-Vanderweele, J. (Jeremy), Walitza, S. (Susanne), Wang, Y. (Ying), Wendland, A. (Annika), Shugart, Y.Y., Miguel, E.C. (Euripedes), Nicolini, H. (Humberto), Oostra, B.A. (Ben), Moessner, R. (Rainald), Wagner, M. (Michael), Ruiz-Linares, A. (Andres), Heutink, P. (Peter), Nestadt, G. (Gerald), Freimer, N.B. (Nelson), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Jenike, M.A. (Michael), Cox, N.J. (Nancy), Hanna, G.L. (Gregory), Brentani, H. (Helena), Scherer, S.W. (Stephen), Arnold, P.D. (Paul), Stewart, S.E., Mathews, C., Knowles, J.A. (James A), Cook, E.H. (Edwin), Pauls, D.L. (David), Wang, K. (Kai), Scharf, J.M., Neale, B.M. (Benjamin), McGrath, L.M., Yu, D. (D.), Marshall, C.R. (Christian), Davis, L.K. (Lea), Thiruvahindrapuram, B. (Bhooma), Li, B. (Bingbin), Cappi, C. (Carolina), Gerber, G. (Gloria), Wolf, A. (Anneke) de, Schroeder, F.A. (Frederick), Osiecki, L. (Lisa), O'Dushlaine, C. (Colm), Kirby, A. (Andrew), Illmann, C. (Cornelia), Haddad, S. (Stephen), Gallagher, P. (Patience), Fagerness, J. (Jesen), Barr, C.L. (Cathy), Bellodi, L. (Laura), Benarroch, F. (Fortu), Bienvenu, O.J. (Oscar), Black, D.W. (Donald), Bloch, J. (Jocelyne), Bruun, R.D. (Ruth), Budman, C.L. (Cathy), Camarena, B. (Beatriz), Cath, D. (Daniëlle), Cavallini, M.C. (Maria), Chouinard, S., Coric, V. (Vladimir), Cullen, C., Delorme, R. (Richard), Denys, D.A.J.P. (Damiaan), Derks, E.M. (Eske), Dion, Y. (Yves), Rosário, M.C. (Maria), Eapen, C.E. (Chundamannil Eapen), Evans, P., Falkai, P. (Peter), Fernandez, T.V. (Thomas), Garrido, H. (Helena), Geller, D. (Daniel), Grabe, H.J. (Hans Jörgen), Grados, M. (Marco), Greenberg, B.D. (Benjamin), Gross-Tsur, V. (Varda), Grünblatt, E. (Edna), Heiman, M.L. (Mark), Hemmings, S.M.J. (Sian), Herrera, L.D. (Luis), Hounie, A.G. (Ana), Jankovic, J. (Joseph), Kennedy, J.L., King, R.A., Kurlan, R., Lanzagorta, N. (Nuria), Leboyer, M. (Marion), Leckman, J.F., Lennertz, L. (Leonhard), Lochner, C. (Christine), Lowe, T.L. (Thomas), Lyon, H.N. (Helen), MacCiardi, F. (Fabio), Maier, W. (Wolfgang), McCracken, J.T. (James), McMahon, W.M. (William), Murphy, D.L. (Dennis), Naarden, A.L. (Allan), Nurmi, E. (Erika), Pakstis, A.J., Pato, C. (Carlos), Piacentini, J. (John), Pittenger, C. (Christopher), Pollak, M.N. (Michael), Reus, V.I. (Victor), Richter, M.A. (Margaret), Riddle, M. (Mark), Robertson, M.M., Rosenberg, D. (David), Rouleau, G.A., Ruhrmann, S. (Stephan), Sampaio, A.S. (Aline), Samuels, J. (Jonathan), Sandor, P. (Paul), Sheppard, B. (Brooke), Singer, H.S. (Harvey), Smit, J.H. (Jan), Stein, D.J. (Dan), Tischfield, J.A. (Jay), Vallada, H. (Homero), Veenstra-Vanderweele, J. (Jeremy), Walitza, S. (Susanne), Wang, Y. (Ying), Wendland, A. (Annika), Shugart, Y.Y., Miguel, E.C. (Euripedes), Nicolini, H. (Humberto), Oostra, B.A. (Ben), Moessner, R. (Rainald), Wagner, M. (Michael), Ruiz-Linares, A. (Andres), Heutink, P. (Peter), Nestadt, G. (Gerald), Freimer, N.B. (Nelson), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Jenike, M.A. (Michael), Cox, N.J. (Nancy), Hanna, G.L. (Gregory), Brentani, H. (Helena), Scherer, S.W. (Stephen), Arnold, P.D. (Paul), Stewart, S.E., Mathews, C., Knowles, J.A. (James A), Cook, E.H. (Edwin), Pauls, D.L. (David), Wang, K. (Kai), Scharf, J.M., and Neale, B.M. (Benjamin)
Abstract: Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p =.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p =.08 in the current study, p =.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
Published: 2014
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13. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author: Davis, L.K. (Lea), Yu, D. (D.), Keenan, C.L. (Clare), Gamazon, E. (Eric), Konkashbaev, A.I. (Anuar), Derks, E.M. (Eske), Neale, B.M. (Benjamin), Yang, J. (Joanna), Lee, S.H. (Sang Hong), Evans, P., Barr, C.L. (Cathy), Bellodi, L. (Laura), Benarroch, F. (Fortu), Berrio, G.B. (Gabriel Bedoya), Bienvenu, O.J. (Oscar), Bloch, J. (Jocelyne), Blom, R.M. (Rianne), Bruun, R.D. (Ruth), Budman, C.L. (Cathy), Camarena, B. (Beatriz), Campbell, D. (Desmond), Cappi, C. (Carolina), Cardona Silgado, J.C. (Julio), Cath, D. (Daniëlle), Cavallini, M.C. (Maria), Chavira, D.A. (Denise), Chouinard, S., Conti, G. (Giario), Cook, E.H. (Edwin), Coric, V. (Vladimir), Cullen, C., Deforce, D. (Dieter), Delorme, R. (Richard), Dion, Y. (Yves), Edlund, C.K. (Christopher), Egberts, K. (Karin), Falkai, P. (Peter), Fernandez, T.V. (Thomas), Gallagher, P. (Patience), Garrido, H. (Helena), Geller, D. (Daniel), Girard, S.L. (Simon), Grabe, H.J. (Hans Jörgen), Grados, M. (Marco), Greenberg, B.D. (Benjamin), Gross-Tsur, V. (Varda), Haddad, S. (Stephen), Heiman, M.L. (Mark), Hemmings, S.M.J. (Sian), Hounie, A.G. (Ana), Illmann, C. (Cornelia), Jankovic, J. (Joseph), Jenike, M.A. (Michael), Kennedy, J.L., King, R.A., Kremeyer, B. (Barbara), Kurlan, R. (Roger), Lanzagorta, N. (Nuria), Leboyer, M. (Marion), Leckman, J.F., Lennertz, L. (Leonhard), Liu, C. (Chunyu), Lochner, C. (Christine), Lowe, T.L. (Thomas), MacCiardi, F. (Fabio), McCracken, J.T. (James), McGrath, L.M., Mesa Restrepo, S.C. (Sandra), Moessner, R. (Rainald), Morgan, J. (John), Muller, H., Murphy, D.L. (Dennis), Naarden, A.L. (Allan), Ochoa, W.C. (William Cornejo), Ophoff, R.A. (Roel), Osiecki, L. (Lisa), Pakstis, A.J., Pato, C. (Carlos), Piacentini, J. (John), Pittenger, C. (Christopher), Pollak, M.N. (Michael), Rauch, S.L. (Scott), Renner, T.J. (Tobias), Reus, V.I. (Victor), Richter, M.A. (Margaret), Riddle, M.A. (Mark), Robertson, M.M., Romero, R. (Roxana), Rosário, M.C. (Maria), Rosenberg, D. (David), Rouleau, G. (Guy), Ruhrmann, S. (Stephan), Ruiz-Linares, A. (Andres), Sampaio, A.S. (Aline), Samuels, J. (Jonathan), Sandor, P., Sheppard, B. (Brooke), Singer, H.S., Smit, J.H. (Jan), Stein, D.J. (Dan), Strengman, E. (Eric), Tischfield, J.A. (Jay), Valencia Duarte, A.V. (Ana), Vallada, H. (Homero), Nieuwerburgh, F. (Filip) van, Veenstra-Vanderweele, J. (Jeremy), Walitza, S. (Susanne), Wang, Y. (Ying), Wendland, A. (Annika), Westenberg, H.G.M. (Herman G.), Shugart, Y.Y., Miguel, E.C. (Euripedes), McMahon, W.M. (William), Wagner, M. (Michael), Nicolini, H. (Humberto), Posthuma, D. (Danielle), Hanna, G.L. (Gregory), Heutink, P. (Peter), Denys, D.A.J.P. (Damiaan), Arnold, P.D. (Paul), Oostra, B.A. (Ben), Nestadt, G. (Gerald), Freimer, N.B. (Nelson), Pauls, D.L. (David), Wray, N.R. (Naomi), Stewart, S.E., Mathews, C.A., Knowles, J.A. (James), Cox, N.J. (Nancy), Scharf, J.M., Davis, L.K. (Lea), Yu, D. (D.), Keenan, C.L. (Clare), Gamazon, E. (Eric), Konkashbaev, A.I. (Anuar), Derks, E.M. (Eske), Neale, B.M. (Benjamin), Yang, J. (Joanna), Lee, S.H. (Sang Hong), Evans, P., Barr, C.L. (Cathy), Bellodi, L. (Laura), Benarroch, F. (Fortu), Berrio, G.B. (Gabriel Bedoya), Bienvenu, O.J. (Oscar), Bloch, J. (Jocelyne), Blom, R.M. (Rianne), Bruun, R.D. (Ruth), Budman, C.L. (Cathy), Camarena, B. (Beatriz), Campbell, D. (Desmond), Cappi, C. (Carolina), Cardona Silgado, J.C. (Julio), Cath, D. (Daniëlle), Cavallini, M.C. (Maria), Chavira, D.A. (Denise), Chouinard, S., Conti, G. (Giario), Cook, E.H. (Edwin), Coric, V. (Vladimir), Cullen, C., Deforce, D. (Dieter), Delorme, R. (Richard), Dion, Y. (Yves), Edlund, C.K. (Christopher), Egberts, K. (Karin), Falkai, P. (Peter), Fernandez, T.V. (Thomas), Gallagher, P. (Patience), Garrido, H. (Helena), Geller, D. (Daniel), Girard, S.L. (Simon), Grabe, H.J. (Hans Jörgen), Grados, M. (Marco), Greenberg, B.D. (Benjamin), Gross-Tsur, V. (Varda), Haddad, S. (Stephen), Heiman, M.L. (Mark), Hemmings, S.M.J. (Sian), Hounie, A.G. (Ana), Illmann, C. (Cornelia), Jankovic, J. (Joseph), Jenike, M.A. (Michael), Kennedy, J.L., King, R.A., Kremeyer, B. (Barbara), Kurlan, R. (Roger), Lanzagorta, N. (Nuria), Leboyer, M. (Marion), Leckman, J.F., Lennertz, L. (Leonhard), Liu, C. (Chunyu), Lochner, C. (Christine), Lowe, T.L. (Thomas), MacCiardi, F. (Fabio), McCracken, J.T. (James), McGrath, L.M., Mesa Restrepo, S.C. (Sandra), Moessner, R. (Rainald), Morgan, J. (John), Muller, H., Murphy, D.L. (Dennis), Naarden, A.L. (Allan), Ochoa, W.C. (William Cornejo), Ophoff, R.A. (Roel), Osiecki, L. (Lisa), Pakstis, A.J., Pato, C. (Carlos), Piacentini, J. (John), Pittenger, C. (Christopher), Pollak, M.N. (Michael), Rauch, S.L. (Scott), Renner, T.J. (Tobias), Reus, V.I. (Victor), Richter, M.A. (Margaret), Riddle, M.A. (Mark), Robertson, M.M., Romero, R. (Roxana), Rosário, M.C. (Maria), Rosenberg, D. (David), Rouleau, G. (Guy), Ruhrmann, S. (Stephan), Ruiz-Linares, A. (Andres), Sampaio, A.S. (Aline), Samuels, J. (Jonathan), Sandor, P., Sheppard, B. (Brooke), Singer, H.S., Smit, J.H. (Jan), Stein, D.J. (Dan), Strengman, E. (Eric), Tischfield, J.A. (Jay), Valencia Duarte, A.V. (Ana), Vallada, H. (Homero), Nieuwerburgh, F. (Filip) van, Veenstra-Vanderweele, J. (Jeremy), Walitza, S. (Susanne), Wang, Y. (Ying), Wendland, A. (Annika), Westenberg, H.G.M. (Herman G.), Shugart, Y.Y., Miguel, E.C. (Euripedes), McMahon, W.M. (William), Wagner, M. (Michael), Nicolini, H. (Humberto), Posthuma, D. (Danielle), Hanna, G.L. (Gregory), Heutink, P. (Peter), Denys, D.A.J.P. (Damiaan), Arnold, P.D. (Paul), Oostra, B.A. (Ben), Nestadt, G. (Gerald), Freimer, N.B. (Nelson), Pauls, D.L. (David), Wray, N.R. (Naomi), Stewart, S.E., Mathews, C.A., Knowles, J.A. (James), Cox, N.J. (Nancy), and Scharf, J.M.
Abstract: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained b
Published: 2013
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14. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author: Davis, LK, Yu, DM, Keenan, CL, Gamazon, ER, Konkashbaev, AI, Derks, EM, Neale, BM, Yang, Jiaqi, Lee, SH, Evans, P, Barr, CL, Bellodi, L, Benarroch, F, Berrio, GB, Bienvenu, OJ, Bloch, MH, Blom, RM, Bruun, RD, Budman, CL, Camarena, B, Campbell, D, Cappi, C, Silgado, JCC, Cath, DC, Cavallini, MC, Chavira, DA, Chouinard, S, Conti, DV, Cook, EH, Coric, V, Cullen, BA, Deforce, D, Delorme, R, Dion, Y, Edlund, CK, Egberts, K, Falkai, P, Fernandez, TV, Gallagher, PJ, Garrido, H, Geller, D, Girard, SL, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Haddad, S, Heiman, GA, Hemmings, SMJ, Hounie, AG, Illmann, C, Jankovic, J, Jenike, MA, Kennedy, JL, King, RA, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Liu, C, Lochner, C, Lowe, TL, Macciardi, F, McCracken, JT, McGrath, LM, Restrepo, SCM, Moessner, R, Morgan, J, Muller, Heike, Murphy, DL, Naarden, AL, Ochoa, WC, Ophoff, RA, Osiecki, L, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, SL, Renner, TJ, Reus, VI, Richter, MA, Riddle, MA, Robertson, MM, Romero, R, Rosario, MC, Rosenberg, D, Rouleau, GA, Ruhrmann, S, Ruiz-Linares, A, Sampaio, AS, Samuels, J, Sandor, P, Sheppard, B, Singer, HS, Smit, JH, Stein, DJ, Strengman, E, Tischfield, JA, Duarte, AVV, Vallada, H, Van Nieuwerburgh, F, Veenstra-VanderWeele, J, Walitza, S, Wang, Y, Wendland, JR, Westenberg, HGM, Shugart, YY, Miguel, EC, McMahon, W, Wagner, M, Nicolini, H, Posthuma, Daniëlle, Hanna, GL, Heutink, P, Denys, D, Arnold, PD, Oostra, Ben, Nestadt, G, Freimer, NB, Pauls, DL, Wray, NR, Stewart, SE, Mathews, CA, Knowles, JA, Cox, NJ, Scharf, JM, Davis, LK, Yu, DM, Keenan, CL, Gamazon, ER, Konkashbaev, AI, Derks, EM, Neale, BM, Yang, Jiaqi, Lee, SH, Evans, P, Barr, CL, Bellodi, L, Benarroch, F, Berrio, GB, Bienvenu, OJ, Bloch, MH, Blom, RM, Bruun, RD, Budman, CL, Camarena, B, Campbell, D, Cappi, C, Silgado, JCC, Cath, DC, Cavallini, MC, Chavira, DA, Chouinard, S, Conti, DV, Cook, EH, Coric, V, Cullen, BA, Deforce, D, Delorme, R, Dion, Y, Edlund, CK, Egberts, K, Falkai, P, Fernandez, TV, Gallagher, PJ, Garrido, H, Geller, D, Girard, SL, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Haddad, S, Heiman, GA, Hemmings, SMJ, Hounie, AG, Illmann, C, Jankovic, J, Jenike, MA, Kennedy, JL, King, RA, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Liu, C, Lochner, C, Lowe, TL, Macciardi, F, McCracken, JT, McGrath, LM, Restrepo, SCM, Moessner, R, Morgan, J, Muller, Heike, Murphy, DL, Naarden, AL, Ochoa, WC, Ophoff, RA, Osiecki, L, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, SL, Renner, TJ, Reus, VI, Richter, MA, Riddle, MA, Robertson, MM, Romero, R, Rosario, MC, Rosenberg, D, Rouleau, GA, Ruhrmann, S, Ruiz-Linares, A, Sampaio, AS, Samuels, J, Sandor, P, Sheppard, B, Singer, HS, Smit, JH, Stein, DJ, Strengman, E, Tischfield, JA, Duarte, AVV, Vallada, H, Van Nieuwerburgh, F, Veenstra-VanderWeele, J, Walitza, S, Wang, Y, Wendland, JR, Westenberg, HGM, Shugart, YY, Miguel, EC, McMahon, W, Wagner, M, Nicolini, H, Posthuma, Daniëlle, Hanna, GL, Heutink, P, Denys, D, Arnold, PD, Oostra, Ben, Nestadt, G, Freimer, NB, Pauls, DL, Wray, NR, Stewart, SE, Mathews, CA, Knowles, JA, Cox, NJ, and Scharf, JM
Abstract: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Published: 2013

15. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Author: Davis, L. K., Yu, D., Keenan, C. L., Gamazon, E. R., Konkashbaev, A. I., Derks, E. M., Neale, B. M., Yang, J., Lee, S. H., Evans, P., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Bloch, M. H., Blom, R. M., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D., Cappi, C., Cardona Silgado, J. C., Cath, D. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Conti, D. V., Cook, E. H., Coric, V., Cullen, B. A., Deforce, D., Delorme, R., Dion, Y., Edlund, C. K., Egberts, K., Falkai, P., Fernandez, T. V., Gallagher, P. J., Garrido, H., Geller, D., Girard, Simon, Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Haddad, S., Heiman, G. A., Hemmings, S. M.J., Hounie, A. G., Illmann, C., Jankovic, J., Jenike, M. A., Kennedy, J. L., King, R. A., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Macciardi, F., McCracken, J. T., McGrath, L. M., Mesa Restrepo, S. C., Moessner, R., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Osiecki, L., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T. J., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Rouleau, G. A., Ruhrmann, S., Ruiz-Linares, A., Sampaio, A. S., Samuels, J., Sandor, P., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Valencia Duarte, A. V., Vallada, H., Van Nieuwerburgh, F., Veenstra-Vanderweele, J., Walitza, S., Wang, Y., Wendland, J. R., Westenberg, H. G.M., Shugart, Y. Y., Miguel, E. C., McMahon, W., Wagner, M., Nicolini, H., Posthuma, D., Hanna, G. L., Heutink, P., Denys, D., Arnold, P. D., Oostra, B. A., Nestadt, G., Freimer, N. B., Pauls, D. L., Wray, N. R., Stewart, S. E., Mathews, C. A., Knowles, J. A., Cox, N. J., Scharf, J. M., Davis, L. K., Yu, D., Keenan, C. L., Gamazon, E. R., Konkashbaev, A. I., Derks, E. M., Neale, B. M., Yang, J., Lee, S. H., Evans, P., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Bloch, M. H., Blom, R. M., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D., Cappi, C., Cardona Silgado, J. C., Cath, D. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Conti, D. V., Cook, E. H., Coric, V., Cullen, B. A., Deforce, D., Delorme, R., Dion, Y., Edlund, C. K., Egberts, K., Falkai, P., Fernandez, T. V., Gallagher, P. J., Garrido, H., Geller, D., Girard, Simon, Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Haddad, S., Heiman, G. A., Hemmings, S. M.J., Hounie, A. G., Illmann, C., Jankovic, J., Jenike, M. A., Kennedy, J. L., King, R. A., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Macciardi, F., McCracken, J. T., McGrath, L. M., Mesa Restrepo, S. C., Moessner, R., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Osiecki, L., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T. J., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Rouleau, G. A., Ruhrmann, S., Ruiz-Linares, A., Sampaio, A. S., Samuels, J., Sandor, P., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Valencia Duarte, A. V., Vallada, H., Van Nieuwerburgh, F., Veenstra-Vanderweele, J., Walitza, S., Wang, Y., Wendland, J. R., Westenberg, H. G.M., Shugart, Y. Y., Miguel, E. C., McMahon, W., Wagner, M., Nicolini, H., Posthuma, D., Hanna, G. L., Heutink, P., Denys, D., Arnold, P. D., Oostra, B. A., Nestadt, G., Freimer, N. B., Pauls, D. L., Wray, N. R., Stewart, S. E., Mathews, C. A., Knowles, J. A., Cox, N. J., and Scharf, J. M.
Abstract: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Published: 2013

16. Genome-Wide Association Study of Gilles de la Tourette Syndrome (IN10-1.002)

Author: Scharf, J., primary, Yu, D., additional, Mathews, C., additional, Neale, B., additional, Stewart, E., additional, Fagerness, J., additional, Evans, P., additional, Gamazon, E., additional, Service, S., additional, Osiecki, L., additional, Illmann, C., additional, Cath, D., additional, King, R., additional, Dion, Y., additional, Sandor, P., additional, Barr, C., additional, Budman, C., additional, Lyon, G., additional, Grados, M., additional, Singer, H., additional, Jankovic, J., additional, Gilbert, D., additional, Hoekstra, P., additional, Heiman, G., additional, Tischfield, J., additional, State, M., additional, Robertson, M., additional, Kurlan, R., additional, Ophoff, R., additional, Gibbs, J. R., additional, Cookson, M., additional, Hardy, J., additional, Singleton, A., additional, Ruiz-Linares, A., additional, Rouleau, G., additional, Heutink, P., additional, Oostra, B., additional, McMahon, W., additional, Freimer, N., additional, COX, N., additional, and Pauls, D., additional
Published: 2012
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17. Genome-Wide Association Study of Gilles de la Tourette Syndrome (S32.006)

Author: Scharf, J., primary, Yu, D., additional, Mathews, C., additional, Neale, B., additional, Stewart, E., additional, Fagerness, J., additional, Evans, P., additional, Gamazon, E., additional, Service, S., additional, Osiecki, L., additional, Illmann, C., additional, Cath, D., additional, King, R., additional, Dion, Y., additional, Sandor, P., additional, Barr, C., additional, Budman, C., additional, Lyon, G., additional, Grados, M., additional, Singer, H., additional, Jankovic, J., additional, Gilbert, D., additional, Hoekstra, P., additional, Heiman, G., additional, Tischfield, J., additional, State, M., additional, Robertson, M., additional, Kurlan, R., additional, Ophoff, R., additional, Gibbs, J. R., additional, Cookson, M., additional, Hardy, J., additional, Singleton, A., additional, Ruiz-Linares, A., additional, Rouleau, G., additional, Heutink, P., additional, Oostra, B., additional, McMahon, W., additional, Freimer, N., additional, COX, N., additional, and Pauls, D., additional
Published: 2012
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18. Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample.

Author: Scharf JM, Moorjani P, Fagerness J, Platko JV, Illmann C, Galloway B, Jenike E, Stewart SE, Pauls DL, Tourette Syndrome International Consortium for Genetics, Scharf, J M, Moorjani, P, Fagerness, J, Platko, J V, Illmann, C, Galloway, B, Jenike, E, Stewart, S E, and Pauls, D L
Published: 2008
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19. Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree

Author: Andrew McQuillin, Dongmei Yu, Jeremiah M. Scharf, Poorva Mudgal, Matthew Halvorsen, David Mataix-Cols, James J. Crowley, Mary M. Robertson, Ashley E. Nordsletten, Manuel Mattheisen, Jin P. Szatkiewicz, Carol A. Mathews, Psychiatric Genomics Consortium TS/OCD Working Group, Aschauer, H., Atzmon, G., Barr, C., Barta, C., Barzilai, N., Batterson, J., Berlin, C., Bodmer, B., Bohnenpoll, J., Brown, L., Bruun, R., Buckner, R., Budman, C., Cath, D., Cheon, K.A., Chouinard, S., Coffey, B., Coppola, G., Cox, N., Crowley, J., Darrow, S., Davis, L., Depienne, C., Dietrich, A., Dion, Y., Elzerman, L., Fernandez, T., Freimer, N., Fremer, C., Fründt, O., Garcia-Delgar, B., Gilbert, D., Grados, M., Greenberg, E., Grice, D., Hagstrøm, J., Halvorsen, M., Hartmann, A., Hebebrand, J., Hedderly, T., Heiman, G., Heyman, I., Hinney, A., Hirschtritt, M., Hoekstra, P., Hong, H., Huang, A., Huyser, C., Ibanez-Gomez, L., Illmann, C., Jankovic, J., Kim, Y., Kim, Y.S., King, R., Knowles, J., Koh, Y.J., Konstantinidis, A., Kook, S., Kuperman, S., Kurlan, R., Leckman, J., Lee, P., Leventhal, B., Ludolph, A., Luðvigsson, P., Lyon, G., Madruga-Garrido, M., Malaty, I., Maras, A., Mataix-Cols, D., Mathews, C., Mattheisen, M., McMahon, W., McQuillin, A., Mir, P., Moessner, R., Morer, A., Mudgal, P., Mueller-Vahl, K., Murphy, T., Münchau, A., Nagy, P., Nawaz, M., Neale, B., Nordsletten, A., Nöthen, M., Okun, M., Ophoff, R., Osiecki, L., Paschou, P., Pato, C., Pato, M., Pauls, D., Plessen, K., Posthuma, D., Richer, P., Rizzo, R., Robertson, M., Roessner, V., Roffman, J., Rouleau, G., Sandor, P., Sæmundsen, E., Scharf, J., Schlögelhofer, M., Shin, E.Y., Singer, H., Smit, J., Smoller, J., Song, D.H., Song, J., Stamenkovic, M., State, M., Stefansson, H., Stefansson, K., Stuhrmann, M., Sul, J., Szatkiewicz, J., Tarnok, Z., Thorarensen, Ó., Tischfield, J., Tsetsos, F., Tübing, J., Visscher, F., Wagner, M., Wanderer, S., Wang, S., Willsey, J., Wolanczyk, T., Woods, D., Woods, M., Worbe, Y., Yu, D., Zelaya, I., Zinner, S., Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Plastic, Reconstructive and Hand Surgery, and Complex Trait Genetics
Subjects: Genetics, Tics, Single-nucleotide polymorphism, Biology, medicine.disease, Tourette syndrome, Genome, Identity by descent, Polymorphism, Single Nucleotide, Pedigree, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Risk Factors, Tic Disorders, medicine, SNP, Humans, Copy-number variation, Polymorphism, Single Nucleotide/genetics, Tourette Syndrome/genetics, Indel, Molecular Biology, Tourette Syndrome
Abstract: Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as "cases" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.
Published: 2021
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20. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author: Sheng Wang, Jeffrey D. Mandell, Yogesh Kumar, Nawei Sun, Montana T. Morris, Juan Arbelaez, Cara Nasello, Shan Dong, Clif Duhn, Xin Zhao, Zhiyu Yang, Shanmukha S. Padmanabhuni, Dongmei Yu, Robert A. King, Andrea Dietrich, Najah Khalifa, Niklas Dahl, Alden Y. Huang, Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Thomas V. Fernandez, Joseph D. Buxbaum, Silvia De Rubeis, Dorothy E. Grice, Jinchuan Xing, Gary A. Heiman, Jay A. Tischfield, Peristera Paschou, A. Jeremy Willsey, Matthew W. State, Mohamed Abdulkadir, Benjamin Bodmer, Yana Bromberg, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Li Deng, Lonneke Elzerman, Carolin Fremer, Blanca Garcia-Delgar, Donald L. Gilbert, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Pieter J. Hoekstra, Hyun Ju Hong, Chaim Huyser, Eun-Joo Kim, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett L Leventhal, Andrea G. Ludolph, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Montana T Morris, Kirsten Müller-Vahl, Alexander Münchau, Tara L. Murphy, Kerstin J. Plessen, Hannah Poisner, Veit Roessner, Stephan J. Sanders, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Joshua K. Thackray, Jennifer Tübing, Frank Visscher, Sina Wanderer, A Jeremy Willsey, Martin Woods, Yeting Zhang, Samuel H. Zinner, Christos Androutsos, Csaba Barta, Luca Farkas, Jakub Fichna, Marianthi Georgitsi, Piotr Janik, Iordanis Karagiannidis, Anastasia Koumoula, Peter Nagy, Joanna Puchala, Renata Rizzo, Natalia Szejko, Urszula Szymanska, Zsanett Tarnok, Vaia Tsironi, Tomasz Wolanczyk, Cezary Zekanowski, Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Matthew E. Hirschtritt, Cornelia Illmann, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, William M. MacMahon, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, Tourette International Collaborative Genetics Study (TIC Genetics), Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE), Tourette Association of America International Consortium for Genetics (TAAICG), Abdulkadir, M., Arbelaez, J., Bodmer, B., Bromberg, Y., Brown, L.W., Cheon, K.A., Coffey, B.J., Deng, L., Dietrich, A., Dong, S., Duhn, C., Elzerman, L., Fernandez, T.V., Fremer, C., Garcia-Delgar, B., Gilbert, D.L., Grice, D.E., Hagstrøm, J., Hedderly, T., Heiman, G.A., Heyman, I., Hoekstra, P.J., Hong, H.J., Huyser, C., Kim, E.J., Kim, Y.K., Kim, Y.S., King, R.A., Koh, Y.J., Kook, S., Kuperman, S., Leventhal, B.L., Ludolph, A.G., Madruga-Garrido, M., Mandell, J.D., Maras, A., Mir, P., Morer, A., Morris, M.T., Müller-Vahl, K., Münchau, A., Murphy, T.L., Nasello, C., Plessen, K.J., Poisner, H., Roessner, V., Sanders, S.J., Shin, E.Y., Song, D.H., Song, J., State, M.W., Sun, N., Thackray, J.K., Tischfield, J.A., Tübing, J., Visscher, F., Wanderer, S., Wang, S., Willsey, A.J., Woods, M., Xing, J., Zhang, Y., Zhao, X., Zinner, S.H., Androutsos, C., Barta, C., Farkas, L., Fichna, J., Georgitsi, M., Janik, P., Karagiannidis, I., Koumoula, A., Nagy, P., Paschou, P., Puchala, J., Rizzo, R., Szejko, N., Szymanska, U., Tarnok, Z., Tsironi, V., Wolanczyk, T., Zekanowski, C., Barr, C.L., Batterson, J.R., Berlin, C., Bruun, R.D., Budman, C.L., Cath, D.C., Chouinard, S., Coppola, G., Cox, N.J., Darrow, S., Davis, L.K., Dion, Y., Freimer, N.B., Grados, M.A., Hirschtritt, M.E., Huang, A.Y., Illmann, C., Kurlan, R., Leckman, J.F., Lyon, G.J., Malaty, I.A., Mathews, C.A., MacMahon, W.M., Neale, B.M., Okun, M.S., Osiecki, L., Pauls, D.L., Posthuma, D., Ramensky, V., Robertson, M.M., Rouleau, G.A., Sandor, P., Scharf, J.M., Singer, H.S., Smit, J., Sul, J.H., and Yu, D.
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, DNA Copy Number Variations, Receptors, Cell Surface, Biology, Genome, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, RARE, SCHIZOPHRENIA, medicine, Humans, Copy-number variation, Child, NEURODEVELOPMENTAL DISORDERS, Gene, lcsh:QH301-705.5, Exome sequencing, 030304 developmental biology, Medicinsk genetik, Sequence (medicine), Genetics, 0303 health sciences, SEVERE INTELLECTUAL DISABILITY, Cadherin, MUTATIONS, AUTISM SPECTRUM DISORDER, Cell Polarity, OBSESSIVE-COMPULSIVE DISORDER, Cadherins, medicine.disease, Pedigree, PREVALENCE, CONGENITAL HEART-DISEASE, GENOME, 030104 developmental biology, lcsh:Biology (General), Schizophrenia, Medical genetics, Female, Cadherins/genetics, Receptors, Cell Surface/genetics, Tourette Syndrome/genetics, Tourette Syndrome/pathology, TIC Genetics, Tourette disorder, cell polarity, copy number variants, de novo variants, gene discovery, microarray genotyping, multiplex, simplex, whole exome sequencing, Medical Genetics, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: SUMMARY We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk., In Brief Wang et al. expand their earlier exome-sequencing work in TD, adding 291 trios and conducting combined analyses suggesting de novo variants carry more risk in individuals with unaffected parents, establishing de novo structural variants as risk factors, identifying CELSR3 as a risk gene, and implicating cell polarity in pathogenesis., Graphical Abstract
Published: 2018

21. Analysis of shared heritability in common disorders of the brain

Author: Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M, Freilinger, Tobias, Ran, Caroline, Gordon, Scott D, Borck, Guntram, Adams, Hieab HH, Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E, Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D, Belin, Andrea C, Van Den Maagdenberg, Arn MJM, Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell J, Catarino, Claudia B, Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N, French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S, Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S, Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M, Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G Neil, Visscher, Frank, Whelan, Christopher D, Zara, Federico, Heinzen, Erin L, Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R, Sharma, Manu, Ryten, Mina, Mok, Kin Y, Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Boraska Perica, Vesna, Thornton, Laura M, Huckins, Laura M, William Rayner, N, Lewis, Cathryn M, Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I, Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H, O'Toole, Julie K, Trace, Sara E, Davis, Oliver SP, Helder, Sietske G, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N, Van Elburg, Annemarie A, Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julià, Antonio, Rabionet, Raquel, Dick, Danielle M, Ripatti, Samuli, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri J, Steen, Vidar M, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A, Mitchell, James, Strober, Michael, Bergen, Andrew W, Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D, Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K, Arias Vasquez, Alejandro, Doyle, Alysa E, Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H, Dalsgaard, Soeren, Børglum, Anders D, Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton HD, Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K, McGough, James J, Grevet, Eugenio H, Medland, Sarah E, Robinson, Elise, Weiss, Lauren A, Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M, Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, De-Luca, Daniel Moreno, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Rogé, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G, Thompson, Robert C, Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E, Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B, Reinbold, Céline S, Fullerton, Janice M, Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B, Gershon, Elliot S, Rice, John, Potash, James B, Zandi, Peter P, Craddock, Nick, Ferrier, I Nicol, Alda, Martin, Rouleau, Guy A, Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M, Cruceanu, Cristiana, Jones, Ian R, Posthuma, Danielle, Andlauer, Till FM, Forstner, Andreas J, Streit, Fabian, Baune, Bernhard T, Air, Tracy, Sinnamon, Grant, Wray, Naomi R, MacIntyre, Donald J, Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M, Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H, Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S, Nauck, Matthias, Schoevers, Robert A, Beekman, Aartjan Tf, Knowles, James A, Viktorin, Alexander, Arnold, Paul, Barr, Cathy L, Bedoya-Berrio, Gabriel, Bienvenu, O Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M, Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L, Hartmann, Andreas, Hirschtritt, Matthew E, Hoekstra, Pieter J, Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J, Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A, Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C, Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S, Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M, Reus, Victor, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Roessner, Veit, Rosário, Maria, Samuels, Jack F, Sandor, Paul, Stein, Dan J, Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R, Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S, McLaughlin, Nicole, Nestadt, Paul S, Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A, Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Lee Chee Keong, Jimmy, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C, Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R, Schall, Ulrich, Schwab, Sibylle G, Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V, Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M, Daly, Mark, Dichgans, Martin, Faraone, Stephen V, Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S, Koeleman, Bobby, Mathews, Carol A, Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W, Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W, Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M, Schott, Jonathan M, Anney, Richard, Elia, Josephine, Grigoroiu-Serbanescu, Maria, Edenberg, Howard J, Murray, Robin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), School of Psychology [Cardiff University], Cardiff University, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), New Jersey Institute of Technology [Newark] (NJIT), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University [New York], Dpt of Neuroscience [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Washington [Seattle], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Children’s Hospital of Philadelphia (CHOP ), University of Kentucky (UK), School of medicine, Duke University [Durham], College of medicine, Brigham Young University (BYU), Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Department of Neurology, Emory University [Atlanta, GA], Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Health sciences center, The University of New Mexico [Albuquerque], Institute for Memory Impairments and Neurological Disorders [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of South Florida [Tampa] (USF), University of Utah School of Medicine [Salt Lake City], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania, Dublin City University [Dublin] (DCU), Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Aristotle University of Thessaloniki, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Dementia Research Centre [London] (DRC), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, MRC Prion Unit [London], Queen's University [Belfast] (QUB), School of Life Sciences, University of Nottingham, UK (UON), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), School of Medicine [Dublin], Trinity College Dublin, Department of Medicine, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), School of Public Health [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University Medical Center (CUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Saarland University [Saarbrücken], Universität Leipzig, School of Medicine [Los Angeles], Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], School of Medecine, Washington University in Saint Louis (WUSTL), Oslo University Hospital [Oslo], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, 23andMe Inc., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Leiden University Medical Center (LUMC), Universiteit Leiden, University-Hospital Munich-Großhadern [München], Karolinska Institutet [Stockholm], Universität Ulm - Ulm University [Ulm, Allemagne], Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Landspitali National University Hospital of Iceland, VU University Medical Center [Amsterdam], Boston VA Research Institute (BVARI), Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Christian-Albrechts-Universität zu Kiel (CAU), Institute of Clinical Molecular Biology, Kiel University, National Institute for Health and Welfare [Helsinki], Harvard T.H. Chan School of Public Health, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], University of Tartu, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Human and Clinical Genetics, Universiteit Leiden-Universiteit Leiden, University of Copenhagen = Københavns Universitet (UCPH), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Discipline of Psychiatry [Dublin], Trinity College Dublin-Trinity College Dublin, Institute of Neurology [London], The University of Hong Kong (HKU), University of Melbourne, Cooper Medical School of Rowan University [Camden] (CMSRU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Antwerp (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Eastern Finland, Universitätsklinikum Bonn (UKB), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Royal College of Surgeons in Ireland (RCSI), University of Southern Denmark (SDU), United Christian Hospital [Hong Kong] (UCH), University of Cincinnati (UC), University of Cologne, Inselspital Bern, University of Wales, Jefferson University Hospitals, University of Liverpool, Medizinische Universität Wien = Medical University of Vienna, National Institutes of Health [Bethesda] (NIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lincoln, University of Newcastle [Callaghan, Australia] (UoN), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Virginia, University of Maryland [Baltimore County] (UMBC), University of Maryland System, Royal Holloway [University of London] (RHUL), University of Edinburgh, Universidade de Lisboa = University of Lisbon (ULISBOA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Split, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), McLean Hospital [Belmont, Ma.], Norwegian Institute of Public Health [Oslo] (NIPH), Università degli Studi di Salerno = University of Salerno (UNISA), University of Bristol [Bristol], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Utrecht University [Utrecht], Azienda Ospedaliera di Padova, Université de Liège, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, National and Kapodistrian University of Athens (NKUA), Charles University [Prague] (CU), SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Flinders University [Adelaide, Australia], Virginia Commonwealth University (VCU), University of Oslo (UiO), University of Bergen (UiB), Weill Medical College of Cornell University [New York], University of North Dakota [Grand Forks] (UND), Oregon Research Institute (ORI), University of California [San Diego] (UC San Diego), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hospital Universitario Mutua de Terrassa, School of Computer Science and Communication [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Jefferson (Philadelphia University + Thomas Jefferson University), University Medical Center Göttingen (UMG), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Universitätsklinikum Frankfurt, Maastricht University [Maastricht], Institute of Psychological Medicine and Clinical Neurosciences, Aarhus University [Aarhus], University of Iowa [Iowa City], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), The Hospital for sick children [Toronto] (SickKids), Hospital de Clínicas de Porto Alegre (HCPA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of British Columbia (UBC), IRCCS Fondazione Stella Maris [Pisa], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Our Lady's Children's Hospital Crumlin (OLCHC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Children’s Hospital Los Angeles [Los Angeles], Yale University [New Haven], Brown University, Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Department of Medical Epidemiology and Biostatistics (MEB), Division of Medical Genetics [Seattle], University of Illinois [Chicago] (UIC), University of Illinois System, Maine Medical Center Research Institute (MMCRI), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Johns Hopkins University School of Medicine [Baltimore], Ludwig Maximilian University [Munich] (LMU), University of Michigan System, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, University of Dundee, National University of Ireland [Galway] (NUI Galway), University Hospital Basel [Basel], Neuroscience Research Australia (NeuRA), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Chicago, Johns Hopkins University (JHU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Dalhousie University [Halifax], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], State University of New York (SUNY), University Hospital of Cologne [Cologne], University of Adelaide, James Cook University (JCU), Institute for Molecular Bioscience, University of Queensland [Brisbane], Greifswald University Hospital, The University of Sydney, University Medical Center Groningen [Groningen] (UMCG), University of Calgary, University Health Network, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidade de São Paulo = University of São Paulo (USP), Ospedale San Raffaele, University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Yale School of Medicine [New Haven, Connecticut] (YSM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cape Town, Cold Spring Harbor Laboratory (CSHL), Universidad de Sevilla / University of Sevilla, University of Florida [Gainesville] (UF), University of Denver, Purdue University [West Lafayette], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Moscow Institute of Physics and Technology [Moscow] (MIPT), Sunnybrook Health Sciences Centre, Federal Institute of São Paulo (IFSP), Democritus University of Thrace (DUTH), Universiteit Gent = Ghent University (UGENT), Medical University of Warsaw - Poland, Sorbonne Université - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institute of Mental Health [Singapore], Universidad de Cantabria [Santander], Tel Aviv University (TAU), University College Cork (UCC), University of Rochester [USA], Statens Serum Institut [Copenhagen], Софийски университет = Sofia University, Russian Academy of Sciences [Moscow] (RAS), Latvian Biomedical Research and Study Centre [Rīga], Vilnius University [Vilnius], Nanyang Technological University [Singapour], Department of Life Sciences, Imperial College London, Jena University Hospital [Jena], Oxford University Hospitals NHS Trust, Schizophrenia Research Institute [Sydney], Faculty of Science, Medicine and Health [Wollongong], University of Wollongong [Australia], City University of Hong Kong [Hong Kong] (CUHK), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials ('Study-specific acknowledgments')., Brainstorm Consortium, University of Kentucky, University of California [Irvine] (UCI), University of California-University of California, University of Pennsylvania [Philadelphia], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig [Leipzig], Johannes Kepler University Linz [Linz] (JKU), University of Helsinki-University of Helsinki, University of Helsinki, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Newcastle [Australia] (UoN), University of Virginia [Charlottesville], Universidade de Lisboa (ULISBOA), Università degli Studi di Salerno (UNISA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Università degli Studi di Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli', Universität Heidelberg [Heidelberg], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, VU University Amsterdam, Universidade de São Paulo (USP), Yale University School of Medicine, Universidad de Sevilla, Universiteit Gent = Ghent University [Belgium] (UGENT), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Tel Aviv University [Tel Aviv], University of Sofia, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Françoi, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S.K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johanne, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthia, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlo, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nichola, Kurth, Tobia, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobia, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H.H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Marku, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfon, Pozo-Rosich, Patricia, Hansen, Thoma, Werge, Thoma, Kaprio, Jaakko, Metspalu, Andre, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. 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Duque, F, Green, A, Klauck, S, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, Moreno-De-Luca, D, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Roge, B, Magalhaes, T, Arking, D, Schulze, T, Thompson, R, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, Mcintosh, A, Bergen, S, Schalling, M, Jamain, S, Maaser, A, Fischer, S, Reinbold, C, Fullerton, J, Guzman-Parra, J, Mayoral, F, Schofield, P, Cichon, S, Mühleisen, T, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, P, Gershon, E, Rice, J, Potash, J, Zandi, P, Craddock, N, Nicol Ferrier, I, Alda, M, Rouleau, G, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, P, Cruceanu, C, Jones, I, Posthuma, D, Andlauer, T, Forstner, A, Streit, F, Baune, B, Air, T, Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, J, Wolanczyk, T, Worbe, Y, Zai, G, Goes, F, Mclaughlin, N, Nestadt, P, Grabe, H, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Kauwe, John S. K., Mcquillin, Andrew, Adams, Hieab H. H., Mccormack, Mark, Bau, Claiton H. D., Mcgough, James J., Mcintosh, Andrew, Andlauer, Till F. M., Macintyre, Donald J., Mcgrath, Lauren, Mclaughlin, Nicole, Delisi, Lynn, Mcdonald, Colm, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), RIKEN Center for Integrative Medical Science, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of South Florida (USF), University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Cardiff University-Medical Research Council, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Johannes Kepler University Linz [linz] (JKU), Washington University in St Louis, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Universitat Autònoma de Barcelona [Barcelona] (UAB), Hôpital Erasme (Bruxelles), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Jagiellonian University [Krakow] (UJ), Technische Universität Dresden (TUD), National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Charles University [Prague], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), University Medicine Goettingen, Università di Bologna [Bologna] (UNIBO), Forschungszentrum Jülich GmbH, UNSW Medicine [Sydney], McGill University, Universidad de Antioquia, University of Florida [Gainesville], Universiteit Gent [Ghent], Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Wollongong, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Anttila, Verneri [0000-0002-0073-4675], Finucane, Hilary K [0000-0003-3864-9828], Walters, Raymond K [0000-0001-8422-6530], Duncan, Laramie [0000-0003-1131-661X], Escott-Price, Valentina [0000-0003-1784-5483], Falcone, Guido J [0000-0002-6407-0302], Gormley, Padhraig [0000-0002-8908-6968], Malik, Rainer [0000-0001-9212-2520], Ripke, Stephan [0000-0003-3622-835X], Wei, Zhi [0000-0001-6059-4267], Yu, Dongmei [0000-0001-7901-4365], Lee, Phil H [0000-0003-1770-3100], Breen, Gerome [0000-0003-2053-1792], Bulik, Cynthia M [0000-0001-7772-3264], Daly, Mark [0000-0002-0949-8752], Dichgans, Martin [0000-0002-0654-387X], Faraone, Stephen V [0000-0002-9217-3982], Holmans, Peter [0000-0003-0870-9412], Koeleman, Bobby [0000-0001-7749-182X], Mathews, Carol A [0000-0003-2208-7058], Sklar, Pamela [0000-0001-9715-4943], Williams, Julie [0000-0002-4069-0259], Wood, Nicholas W [0000-0002-9500-3348], Cotsapas, Chris [0000-0002-7772-5910], Smoller, Jordan W [0000-0002-0381-6334], Sullivan, Patrick [0000-0002-6619-873X], Rosand, Jonathan [0000-0002-1014-9138], Corvin, Aiden [0000-0001-6717-4089], Neale, Benjamin M [0000-0003-1513-6077], and Apollo - University of Cambridge Repository
Subjects: Etiology, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, body-mass index, genetics [Mental Disorders], Disorders of the Brain, Risks factors, classification [Mental Disorders], MESH: Quantitative Trait, Heritable, MESH: Risk Factors, Risk Factors, MESH: Genetic Variation, alzheimers-disease, 610 Medicine & health, bipolar disorder, Brain Diseases, deficit hyperactivity disorder, Multidisciplinary, Mental Disorders, genetics [Brain Diseases], Brain Disease, Brain, Genetic Variation, Genome-Wide Association Study, Humans, Phenotype, Quantitative Trait, Heritable, Psychiatric Disorders, anorexia-nervosa, Mental Disorder, Psychiatric Genomics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], long-term survival, Engineering sciences. Technology, Human, General Science & Technology, population-based twin, diagnosis [Mental Disorders], MESH: Phenotype, Neurological Disorders, Quantitative Trait, MD Multidisciplinary, MESH: Mental Disorders, diagnosis [Brain Diseases], Heritable, genetic correlations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, major depressive disorder, Risk Factor, Brain Diseases/classification, Brain Diseases/diagnosis, Brain Diseases/genetics, Mental Disorders/classification, Mental Disorders/diagnosis, Mental Disorders/genetics, classification [Brain Diseases], Perturbações do Desenvolvimento Infantil e Saúde Mental, ddc:320, MESH: Genome-Wide Association Study, genome-wide association, Brainstorm Consortium, Genetic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities’ assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important “scaffolding” to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders.
Published: 2018
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22. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

Author: 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, 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, and EMGO+ - Mental Health
Subjects: 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
Abstract: 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.
Published: 2015
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23. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study

Author: McGrath, Lauren M, Yu, Dongmei, Marshall, Christian, Davis, Lea K, Thiruvahindrapuram, Bhooma, Li, Bingbin, Cappi, Carolina, Gerber, Gloria, Wolf, Aaron, Schroeder, Frederick A, Osiecki, Lisa, O'Dushlaine, Colm, Kirby, Andrew, Illmann, Cornelia, Haddad, Stephen, Gallagher, Patience, Fagerness, Jesen A, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Bienvenu, O Joseph, Black, Donald W, Bloch, Michael H, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Cath, Danielle C, Cavallini, Maria C, Chouinard, Sylvain, Coric, Vladimir, Cullen, Bernadette, Delorme, Richard, Denys, Damiaan, Derks, Eske M, Dion, Yves, Rosário, Maria C, Eapen, Valsama, Evans, Patrick, Falkai, Peter, Fernandez, Thomas V, Garrido, Helena, Geller, Daniel, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Grünblatt, Edna, Heiman, Gary A, Hemmings, Sian M J, Herrera, Luis D, Hounie, Ana G, Jankovic, Joseph, Kennedy, James L, King, Robert A, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Lochner, Christine, Lowe, Thomas L, Lyon, Gholson J, Macciardi, Fabio, Maier, Wolfgang, McCracken, James T, McMahon, William, Murphy, Dennis L, Naarden, Allan L, Neale, Benjamin M, Nurmi, Erika, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Reus, Victor I, Richter, Margaret A, Riddle, Mark, Robertson, Mary M, Rosenberg, David, Rouleau, Guy A, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S, Smit, Jan H, Stein, Dan J, Tischfield, Jay A, Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R, Shugart, Yin Yao, Miguel, Euripedes C, Nicolini, Humberto, Oostra, Ben A, Moessner, Rainald, Wagner, Michael, Ruiz-Linares, Andres, Heutink, Peter, Nestadt, Gerald, Freimer, Nelson, Petryshen, Tracey, Posthuma, Danielle, Jenike, Michael A, Cox, Nancy J, Hanna, Gregory L, Brentani, Helena, Scherer, Stephen W, Arnold, Paul D, Stewart, S Evelyn, Mathews, Carol A, Knowles, James A, Cook, Edwin H, Pauls, David L, Wang, Kai, Scharf, Jeremiah M, Leerstoel Hout, Sub String Theory Cosmology and ElemPart, Experimental psychopathology, University of Zurich, Scharf, Jeremiah M, Leerstoel Hout, Sub String Theory Cosmology and ElemPart, Experimental psychopathology, Clinical Genetics, Child and Adolescent Psychiatry / Psychology, Artificial intelligence, Complex Trait Genetics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Functional Genomics, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, APH - Amsterdam Public Health, Netherlands Institute for Neuroscience (NIN), Mcgrath, Lm, Yu, D, Marshall, C, Davis, Lk, Thiruvahindrapuram, B, Li, B, Cappi, C, Gerber, G, Wolf, A, Schroeder, Fa, Osiecki, L, O'Dushlaine, C, Kirby, A, Illmann, C, Haddad, S, Gallagher, P, Fagerness, Ja, Barr, Cl, Bellodi, Laura, Benarroch, F, Bienvenu, Oj, Black, Dw, Bloch, Mh, Bruun, Rd, Budman, Cl, Camarena, B, Cath, Dc, Cavallini, Mc, Chouinard, S, Coric, V, Cullen, B, Delorme, R, Denys, D, Derks, Em, Dion, Y, Rosário, Mc, Eapen, V, Evans, P, Falkai, P, Fernandez, Tv, Garrido, H, Geller, D, Grabe, Hj, Grados, Ma, Greenberg, Bd, Gross Tsur, V, Grünblatt, E, Heiman, Ga, Hemmings, Sm, Herrera, Ld, Hounie, Ag, Jankovic, J, Kennedy, Jl, King, Ra, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, Jf, Lennertz, L, Lochner, C, Lowe, Tl, Lyon, Gj, Macciardi, F, Maier, W, Mccracken, Jt, Mcmahon, W, Murphy, Dl, Naarden, Al, Neale, Bm, Nurmi, E, Pakstis, Aj, Pato, Mt, Pato, Cn, Piacentini, J, Pittenger, C, Pollak, Y, Reus, Vi, Richter, Ma, Riddle, M, Robertson, Mm, Rosenberg, D, Rouleau, Ga, Ruhrmann, S, Sampaio, A, Samuels, J, Sandor, P, Sheppard, B, Singer, H, Smit, Jh, Stein, Dj, Tischfield, Ja, Vallada, H, Veenstra VanderWeele, J, Walitza, S, Wang, Y, Wendland, Jr, Shugart, Yy, Miguel, Ec, Nicolini, H, Oostra, Ba, Moessner, R, Wagner, M, Ruiz Linares, A, Heutink, P, Nestadt, G, Freimer, N, Petryshen, T, Posthuma, D, Jenike, Ma, Cox, Nj, Hanna, Gl, Brentani, H, Scherer, Sw, Arnold, Pd, Stewart, Se, Mathews, Ca, Knowles, Ja, Cook, Eh, Pauls, Dl, Wang, K, Scharf, J. M., Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Mental health
Subjects: Oncology, Male, medicine.medical_specialty, diagnosis [Tourette Syndrome], Adolescent, DNA Copy Number Variations, Genome-wide association study, 610 Medicine & health, Tourette syndrome, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 2738 Psychiatry and Mental Health, SDG 3 - Good Health and Well-being, Obsessive compulsive, Genetic etiology, Internal medicine, mental disorders, Developmental and Educational Psychology, medicine, Humans, Genetic Predisposition to Disease, genetics, Copy-number variation, ddc:610, Genetics, genetics [Obsessive-Compulsive Disorder], 3204 Developmental and Educational Psychology, copy number variation, 10058 Department of Child and Adolescent Psychiatry, medicine.disease, 16p13.11, Diagnostic and Statistical Manual of Mental Disorders, obsessive-compulsive disorder, Psychiatry and Mental health, genetics [Tourette Syndrome], Schizophrenia, Autism, Female, Psychology, Genome-Wide Association Study, diagnosis [Obsessive-Compulsive Disorder]
Abstract: Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (
Published: 2014
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24. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Author: Patrick Evans, Jay A. Tischfield, Anuar Konkashbaev, Richard Delorme, Sandra Catalina Mesa Restrepo, Margaret A. Richter, Gregory L. Hanna, Allan L. Naarden, Michele T. Pato, Jian Yang, Denise A. Chavira, Damiaan Denys, Paul Sandor, Michael A. Jenike, Sian M. J. Hemmings, Paul D. Arnold, Stephan Ruhrmann, H.G.M. Westenberg, Yves Dion, Cathy L. Barr, Andres Ruiz-Linares, Brooke Sheppard, Leonhard Lennertz, Eske M. Derks, Lauren M. McGrath, Barbara Kremeyer, Marion Leboyer, Victor I. Reus, Cornelia Illmann, S. Evelyn Stewart, Dan J. Stein, Ana Gabriela Hounie, James T. McCracken, R. Kurlan, Chunyu Liu, Aline S. Sampaio, Thomas L. Lowe, Benjamin M. Neale, Yehuda Pollak, Desmond Campbell, Fabio Macciardi, Mary M. Robertson, Benjamin D. Greenberg, Ben A. Oostra, Rainald Moessner, Gary A. Heiman, Nuria Lanzagorta, Sylvain Chouinard, Rianne M. Blom, Karin Egberts, Carlos N. Pato, David V. Conti, Carol A. Mathews, Ying Wang, Marco A. Grados, Julio C. Cardona Silgado, S. Hong Lee, H. Müller, Eric R. Gamazon, Humberto Nicolini, Jan Smit, Euripedes Constantino Miguel, Jens R. Wendland, Cathy L. Budman, Laura Bellodi, Danielle Posthuma, Jubel Morgan, David R. Rosenberg, John Piacentini, Hans J. Grabe, Mark A. Riddle, Beatriz Camarena, Naomi R. Wray, Eric Strengman, Dennis L. Murphy, Simon Girard, Christine Lochner, Ruth D. Bruun, Joseph Jankovic, Edwin H. Cook, William M. McMahon, Scott L. Rauch, James F. Leckman, Peter Falkai, Fortu Benarroch, Christopher K. Edlund, Gabriel Bedoya Berrío, Homero Vallada, Susanne Walitza, Nelson B. Freimer, Stephen A. Haddad, Yin Yao Shugart, Danielle C. Cath, Nancy J. Cox, Varda Gross-Tsur, Guy A. Rouleau, Bernadette Cullen, Michael H. Bloch, Dieter Deforce, David L. Pauls, Thomas V. Fernandez, Roel A. Ophoff, Filip Van Nieuwerburgh, Gerald Nestadt, Dongmei Yu, Helena Garrido, Robert A. King, James L. Kennedy, Clare L. Keenan, Lisa Osiecki, Jack Samuels, Jeremy Veenstra-VanderWeele, Ana V. Valencia Duarte, James A. Knowles, Patience J. Gallagher, Carolina Cappi, Maria Conceição do Rosário, Andrew J. Pakstis, Christopher Pittenger, Michael Wagner, Jeremiah M. Scharf, Daniel A. Geller, Vladimir Coric, Tobias J. Renner, Oscar J. Bienvenu, Roxana Romero, William Cornejo Ochoa, Peter Heutink, Lea K. Davis, Harvey S. Singer, Maria Cristina Cavallini, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, Department of Psychiatry and Mental Health, Faculty of Health Sciences, Univ Chicago, Harvard Univ, Broad Inst Harvard & MIT, Univ Amsterdam, Massachusetts Gen Hosp, Univ Queensland, Univ Hlth Network, Hosp Sick Children, Univ Vita Salute San Raffaele, Hadassah Hebrew Univ Med Ctr, Univ Pontificia Bolivariana, Johns Hopkins Univ, Yale Univ, North Shore Long Isl Jewish Med Ctr, NYU Med Ctr, North Shore Long Isl Jewish Hlth Syst, Hofstra Univ, Inst Nacl Psiquiatria Ramon de la Fuente Muniz, UCL, Univ Hong Kong, Universidade de São Paulo (USP), Vrije Univ Amsterdam, Univ Utrecht, Altrecht Acad Anxiety Ctr, Univ Milan, Univ Calif Los Angeles, Univ Calif San Diego, Univ Montreal, Univ Illinois, Univ Ghent, Inst Pasteur, French Natl Sci Fdn, Hop Robert Debre, Univ Wurzburg, Univ Munich, Univ Med Greifswald, Butler Hosp, Shaare Zedek Med Ctr, Rutgers State Univ, Univ Stellenbosch, Baylor Coll Med, Ctr Addict & Mental Hlth, Univ Toronto, Overlook Hosp, Carracci Med Grp, Inst Mondor Rech Biomed, Univ Bonn, Univ Calif San Francisco, UCI, Univ Utah, NIMH Intramural Res Program, Med City Dallas Hosp, Univ Med Ctr, Univ So Calif, Partners Psychiat & McLean Hosp, Sunnybrook Hlth Sci Ctr, St George Hosp, Sch Med, Hosp Nacl Ninos Dr Carlos Saenz Herrera, Universidade Federal de São Paulo (UNIFESP), Wayne State Univ, Detroit Med Ctr, McGill Univ, Univ Cologne, Universidade Federal da Bahia (UFBA), Youthdale Treatment Ctr, Johns Hopkins Univ Sch Med, Univ Cape Town, Univ Med Ctr Utrecht, Vanderbilt Univ, Univ Zurich, Inst Royal Netherlands Acad Arts & Sci NIN KNAW, Natl Inst Genom Med SAP, Vrije Univ Amsterdam Med Ctr, Erasmus Univ, Univ Michigan, German Ctr Neurodegenerat Dis, Erasmus MC, Univ British Columbia, Brigham & Womens Hosp, Davis, Lk, Yu, D, Keenan, Cl, Gamazon, Er, Konkashbaev, Ai, Derks, Em, Neale, Bm, Yang, J, Lee, Sh, Evans, P, Barr, Cl, Bellodi, Laura, Benarroch, F, Berrio, Gb, Bienvenu, Oj, Bloch, Mh, Blom, Rm, Bruun, Rd, Budman, Cl, Camarena, B, Campbell, D, Cappi, C, Cardona Silgado, Jc, Cath, Dc, Cavallini, Mc, Chavira, Da, Chouinard, S, Conti, Dv, Cook, Eh, Coric, V, Cullen, Ba, Deforce, D, Delorme, R, Dion, Y, Edlund, Ck, Egberts, K, Falkai, P, Fernandez, Tv, Gallagher, Pj, Garrido, H, Geller, D, Girard, Sl, Grabe, Hj, Grados, Ma, Greenberg, Bd, Gross Tsur, V, Haddad, S, Heiman, Ga, Hemmings, Sm, Hounie, Ag, Illmann, C, Jankovic, J, Jenike, Ma, Kennedy, Jl, King, Ra, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, Jf, Lennertz, L, Liu, C, Lochner, C, Lowe, Tl, Macciardi, F, Mccracken, Jt, Mcgrath, Lm, Mesa Restrepo, Sc, Moessner, R, Morgan, J, Muller, H, Murphy, Dl, Naarden, Al, Ochoa, Wc, Ophoff, Ra, Osiecki, L, Pakstis, Aj, Pato, Mt, Pato, Cn, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, Sl, Renner, Tj, Reus, Vi, Richter, Ma, Riddle, Ma, Robertson, Mm, Romero, R, Rosàrio, Mc, Rosenberg, D, Rouleau, Ga, Ruhrmann, S, Ruiz Linares, A, Sampaio, A, Samuels, J, Sandor, P, Sheppard, B, Singer, H, Smit, Jh, Stein, Dj, Strengman, E, Tischfield, Ja, Valencia Duarte, Av, Vallada, H, Van Nieuwerburgh, F, Veenstra Vanderweele, J, Walitza, S, Wang, Y, Wendland, Jr, Westenberg, Hg, Shugart, Yy, Miguel, Ec, Mcmahon, W, Wagner, M, Nicolini, H, Posthuma, D, Hanna, Gl, Heutink, P, Denys, D, Arnold, Pd, Oostra, Ba, Nestadt, G, Freimer, Nb, Pauls, Dl, Wray, Nr, Stewart, Se, Mathews, Ca, Knowles, Ja, Cox, Nj, Scharf, Jm, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Davis, Lea K, Yu, Dongmei, Keenan, Clare L, Gamazon, Eric R, Lee, S Hong, Scharf, Jeremiah M, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Other departments, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, and Graduate School
Subjects: Cancer Research, Obsessive-Compulsive Disorder, COMPLEX DISEASES, Genome-wide association study, heritability, Genome-wide association studies, neurobehavioral disorders, COMMON SNPS, 0302 clinical medicine, Gene Frequency, Missing heritability problem, MISSING HERITABILITY, Cerebellum, Heritability of autism, BRAIN, Genetics (clinical), Genetics, ddc:616, Genetics & Heredity, 0303 health sciences, Chromosome 15, humanities, FAMILY, obsessive-compulsive disorder, genetics [Tourette Syndrome], Phenotype, NEUROPSYCHIATRIC DISORDERS, GENÔMICA, Research Article, EXPRESSION, lcsh:QH426-470, SNP, Biology, Quantitative trait locus, Genome-wide Complex Trait Analysis, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Chromosomes, TIC DISORDERS, 03 medical and health sciences, Quantitative Trait, Heritable, mental disorders, genetic risk factors, Humans, ddc:610, AUTISM, Variant genotypes, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, genetics [Obsessive-Compulsive Disorder], Tourette syndrome, Parietal lobe, Biology and Life Sciences, Heritability, Genetic architecture, Minor allele frequency, Trastorno Obsesivo Compulsivo, lcsh:Genetics, pathology [Obsessive-Compulsive Disorder], genetic variation, pathology [Tourette Syndrome], Síndrome de Tourette, 030217 neurology & neurosurgery, GILLES, Genome-Wide Association Study, Tourette Syndrome
Abstract: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures., Author Summary Family and twin studies have shown that genetic risk factors are important in the development of Tourette Syndrome (TS) and obsessive compulsive disorder (OCD). However, efforts to identify the individual genetic risk factors involved in these two neuropsychiatric disorders have been largely unsuccessful. One possible explanation for this is that many genetic variations scattered throughout the genome each contribute a small amount to the overall risk. For TS and OCD, the genetic architecture (characterized by the number, frequency, and distribution of genetic risk factors) is presently unknown. This study examined the genetic architecture of TS and OCD in a variety of ways. We found that rare genetic changes account for more genetic risk in TS than in OCD; certain chromosomes contribute to OCD risk more than others; and variants that influence the level of genes expressed in two regions of the brain can account for a significant amount of risk for both TS and OCD. Results from this study might help in determining where, and what kind of variants are individual risk factors for TS and OCD and where they might be located in the human genome.
Published: 2013
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25. Relationships between the menstrual cycle and neuropsychiatric and physical symptoms in females with Tourette syndrome.

Author: Noriega-Makarskyy DT, Realbuto E, Kaylor A, Osiecki L, Essa A, Yu D, Illmann C, Mathews CA, and Scharf JM
Abstract: Background: The effects of the menstrual cycle on neuropsychiatric and physical symptoms have been examined in multiple psychiatric illnesses, but research on Tourette syndrome (TS) and menstruation is limited and inconclusive. One study published in 1992 reported that 34% of female respondents experienced tic fluctuations with their menstrual cycles; however, a subsequent 2001 study found no significant relationship between menstrual cycle-related hormonal changes and tic symptoms across participants. There has been no further published exploration of this topic in the intervening 20+ years, and thus these discrepant results have not been reconciled. The current study aimed to assess tic changes across the menstrual cycle and to explore clinical predictors of tic fluctuations in adult females with TS., Methods: An online survey was completed by 112 of 315 eligible female adults with TS. Respondents were asked to share their age of TS symptom onset, history of OCD and ADHD diagnoses, and current tic symptoms and severity. Participants also retrospectively reported their experiences with fluctuations in tics and other physical and psychiatric symptoms over the course of the menstrual cycle., Results: 26% of the 112 respondents endorsed tic changes in relation to their menstrual cycles. Univariable and multivariable logistic regression demonstrated that higher current tic severity and impairment as well as co-occurring cycle-related mood and anxiety changes significantly predicted the presence of self-reported tic fluctuations during the menstrual cycle., Discussion: Results suggest that some females with TS experience changes in tic symptoms during their menstrual cycles, although future research is required to clarify the complex relationships between the menstrual cycle, tics, and other psychiatric symptoms. The low response rate, retrospective recall of symptoms, and lack of information about hormonal influences such as contraceptives and menopause are notable study limitations., Competing Interests: JS is a member of the Tourette Association of America Scientific Advisory Board and has received financial support to attend the TAA Centers of Excellence annual meeting. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Noriega-Makarskyy, Realbuto, Kaylor, Osiecki, Essa, Yu, Illmann, Mathews and Scharf.)
Published: 2025
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26. Relationship between adverse childhood experiences and symptom severity in adult men with Tourette Syndrome.

Author: Yang K, Essa A, Noriega D, Yu D, Osiecki L, Gauvin CA, Illmann C, Bortolato M, Dunn EC, Mathews CA, and Scharf JM
Subjects: Adult, Genome-Wide Association Study, Humans, Male, Retrospective Studies, Severity of Illness Index, Adverse Childhood Experiences, Tics, Tourette Syndrome diagnosis
Abstract: Childhood adversity is associated with the development or expression of many neuropsychiatric disorders, including those with strong genetic underpinnings. Despite reported associations between perceived stress and tic severity, the relationship between potentially traumatic events in childhood and Tourette Syndrome (TS), a highly heritable neuropsychiatric disorder, is unknown. This study aimed to assess whether exposure to eight categories of adverse childhood experiences (ACEs) is associated with TS severity and impairment, and whether TS genetic risk modifies this association. Online survey data were collected from 351 adult males with TS who previously participated in genetic studies. Participants completed the ACE questionnaire and a lifetime version of the Yale Global Tic Severity Scale (YGTSS). Demographic and relevant health data were assessed; polygenic risk scores (PRS) measuring aggregated TS genetic risk were derived using genome-wide association data. Univariable and multivariable linear regressions examined the relationships between childhood adversity and retrospectively recalled worst-ever tic severity and impairment, adjusting for covariates. Potential gene-by-environment (GxE) interactions between ACE and PRS were estimated. After covariate adjustment, there was a significant graded dose-response relationship between ACE Scores and increases in lifetime worst-ever tic severity and impairment. There was some evidence that TS genetic risk moderated the relationship between ACE Score and tic impairment, but not tic severity, particularly for individuals with higher TS polygenic risk. We provide evidence that childhood adversity is associated with higher lifetime TS severity and impairment, although future longitudinal studies with genetically-sensitive designs are needed to determine whether these relationships are causal and/or directional., Competing Interests: Declaration of competing interest Drs. Mathews, Scharf and Bortolato have received travel and grant support from the Tourette Association of America (TAA). Drs. Mathews and Scharf are members of the TAA Scientific Advisory Board. Drs. Illmann, Dunn, Gauvin and Ms. Yang, Essa, Noriega and Osiecki report no potential conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)
Published: 2022
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27. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Author: Claudio-Campos K, Stevens D, Koo SW, Valko A, Bienvenu OJ, Budman CB, Cath DC, Darrow S, Geller D, Goes FS, Grados MA, Greenberg BD, Greenberg E, Hirschtritt ME, Illmann C, Ivankovic F, King RA, Knowles JA, Krasnow J, Lee PC, Lyon GJ, McCracken JT, Robertson MM, Osiecki L, Riddle MA, Rouleau G, Sandor P, Nestadt G, Samuels J, Scharf JM, and Mathews CA
Subjects: Comorbidity, Humans, Attention Deficit Disorder with Hyperactivity epidemiology, Obsessive-Compulsive Disorder epidemiology, Tic Disorders epidemiology, Tics epidemiology, Tourette Syndrome epidemiology
Abstract: Background: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation., Objective: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT., Methods: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature., Results: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates., Conclusions: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Published: 2021
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28. Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Author: Tsetsos F, Yu D, Sul JH, Huang AY, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau GA, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados MA, Singer HS, Nöthen MM, Hebebrand J, Hinney A, King RA, Fernandez TV, Barta C, Tarnok Z, Nagy P, Depienne C, Worbe Y, Hartmann A, Budman CL, Rizzo R, Lyon GJ, McMahon WM, Batterson JR, Cath DC, Malaty IA, Okun MS, Berlin C, Woods DW, Lee PC, Jankovic J, Robertson MM, Gilbert DL, Brown LW, Coffey BJ, Dietrich A, Hoekstra PJ, Kuperman S, Zinner SH, Wagner M, Knowles JA, Jeremy Willsey A, Tischfield JA, Heiman GA, Cox NJ, Freimer NB, Neale BM, Davis LK, Coppola G, Mathews CA, Scharf JM, Paschou P, Barr CL, Batterson JR, Berlin C, Budman CL, Cath DC, Coppola G, Cox NJ, Darrow S, Davis LK, Dion Y, Freimer NB, Grados MA, Greenberg E, Hirschtritt ME, Huang AY, Illmann C, King RA, Kurlan R, Leckman JF, Lyon GJ, Malaty IA, Mathews CA, McMahon WM, Neale BM, Okun MS, Osiecki L, Robertson MM, Rouleau GA, Sandor P, Scharf JM, Singer HS, Smit JH, Sul JH, Yu D, Aschauer HAH, Barta C, Budman CL, Cath DC, Depienne C, Hartmann A, Hebebrand J, Konstantinidis A, Mathews CA, Müller-Vahl K, Nagy P, Nöthen MM, Paschou P, Rizzo R, Rouleau GA, Sandor P, Scharf JM, Schlögelhofer M, Stamenkovic M, Stuhrmann M, Tsetsos F, Tarnok Z, Wolanczyk T, Worbe Y, Brown L, Cheon KA, Coffey BJ, Dietrich A, Fernandez TV, Garcia-Delgar B, Gilbert D, Grice DE, Hagstrøm J, Hedderly T, Heiman GA, Heyman I, Hoekstra PJ, Huyser C, Kim YK, Kim YS, King RA, Koh YJ, Kook S, Kuperman S, Leventhal BL, Madruga-Garrido M, Mir P, Morer A, Münchau A, Plessen KJ, Roessner V, Shin EY, Song DH, Song J, Tischfield JA, Willsey AJ, Zinner S, Aschauer H, Barr CL, Barta C, Batterson JR, Berlin C, Brown L, Budman CL, Cath DC, Coffey BJ, Coppola G, Cox NJ, Darrow S, Davis LK, Depienne C, Dietrich A, Dion Y, Fernandez T, Freimer NB, Gilbert D, Grados MA, Greenberg E, Hartmann A, Hebebrand J, Heiman G, Hirschtritt ME, Hoekstra P, Huang AY, Illmann C, Jankovic J, King RA, Kuperman S, Lee PC, Lyon GJ, Malaty IA, Mathews CA, McMahon WM, Müller-Vahl K, Nagy P, Neale BM, Nöthen MM, Okun MS, Osiecki L, Paschou P, Rizzo R, Robertson MM, Rouleau GA, Sandor P, Scharf JM, Schlögelhofer M, Singer HS, Stamenkovic M, Stuhrmann M, Sul JH, Tarnok Z, Tischfield J, Tsetsos F, Willsey AJ, Woods D, Worbe Y, Yu D, and Zinner S
Subjects: Genome-Wide Association Study, Genotype, Humans, Neurons, Tourette Syndrome genetics
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.
Published: 2021
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29. Efficacy of Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in ER-positive Breast Cancer: Results From a Prospective Institutional Database.

Author: LeVasseur N, Willemsma KA, Li H, Gondara L, Yip WC, Illmann C, Chia SK, and Simmons C
Subjects: Adult, Aged, Aged, 80 and over, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Case-Control Studies, Chemotherapy, Adjuvant, Female, Follow-Up Studies, Humans, Middle Aged, Prognosis, Prospective Studies, Antineoplastic Agents, Hormonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology, Databases, Factual, Neoadjuvant Therapy methods, Receptors, Estrogen metabolism
Abstract: Background: Although neoadjuvant chemotherapy (NACT) has been established as a standard for medically fit patients with locally advanced breast cancer, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Rates of pathologic complete response (pCR) are known to be low, but data regarding down-staging and long-term outcomes are inconsistent., Patients and Methods: A prospective institutional database of patients with breast cancer treated with neoadjuvant therapy from 2012 to 2017 was analyzed to identify patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Patients who received NET were compared with those who received NACT. A matched analysis (age, stage, grade) was performed to compare rates of down-staging, pCR, breast conserving surgery, and CPS+EG scores., Results: A total of 176 patients met eligibility criteria. Of these, 111 (63%) patients received NACT, 51 (29%) received NET, and 14 (8%) received both sequentially. Women prescribed NET were older (65.5 vs. 51.2 years; P < .0001) and presented with lower clinical stage (P < .0001). The median duration of NET was 90 days. When matched, clinical down-staging was more frequent with NACT (20/51; 39%) compared with NET (11/51; 22%) (P = .032). Of these, 2% achieved pCR in each cohort. Conversion rates to breast conserving surgery eligibility were low (8% and 13% with NET and NACT; P = .70). No significant differences in CPS+EG scores were identified., Conclusions: Significantly higher rates of down-staging were achieved with NACT compared with NET when patients were matched. This study highlights the importance of establishing tumor biology and the need for biomarkers that can be used as predictive tools to inform treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)
Published: 2019
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30. Interrogating the Genetic Determinants of Tourette's Syndrome and Other Tic Disorders Through Genome-Wide Association Studies.

Author: Yu D, Sul JH, Tsetsos F, Nawaz MS, Huang AY, Zelaya I, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau G, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados M, Singer HS, Nöthen MM, Hebebrand J, Hinney A, King RA, Fernandez TV, Barta C, Tarnok Z, Nagy P, Depienne C, Worbe Y, Hartmann A, Budman CL, Rizzo R, Lyon GJ, McMahon WM, Batterson JR, Cath DC, Malaty IA, Okun MS, Berlin C, Woods DW, Lee PC, Jankovic J, Robertson MM, Gilbert DL, Brown LW, Coffey BJ, Dietrich A, Hoekstra PJ, Kuperman S, Zinner SH, Luðvigsson P, Sæmundsen E, Thorarensen Ó, Atzmon G, Barzilai N, Wagner M, Moessner R, Ophoff R, Pato CN, Pato MT, Knowles JA, Roffman JL, Smoller JW, Buckner RL, Willsey AJ, Tischfield JA, Heiman GA, Stefansson H, Stefansson K, Posthuma D, Cox NJ, Pauls DL, Freimer NB, Neale BM, Davis LK, Paschou P, Coppola G, Mathews CA, and Scharf JM
Subjects: Case-Control Studies, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Multifactorial Inheritance genetics, Polymorphism, Single Nucleotide genetics, Risk Factors, Severity of Illness Index, fms-Like Tyrosine Kinase 3 genetics, Tic Disorders genetics, Tourette Syndrome genetics
Abstract: Objective: Tourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity., Methods: GWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined., Results: GWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects., Conclusions: Modulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.
Published: 2019
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31. Analysis of shared heritability in common disorders of the brain.

Author: Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, Malik R, Patsopoulos NA, Ripke S, Wei Z, Yu D, Lee PH, Turley P, Grenier-Boley B, Chouraki V, Kamatani Y, Berr C, Letenneur L, Hannequin D, Amouyel P, Boland A, Deleuze JF, Duron E, Vardarajan BN, Reitz C, Goate AM, Huentelman MJ, Kamboh MI, Larson EB, Rogaeva E, St George-Hyslop P, Hakonarson H, Kukull WA, Farrer LA, Barnes LL, Beach TG, Demirci FY, Head E, Hulette CM, Jicha GA, Kauwe JSK, Kaye JA, Leverenz JB, Levey AI, Lieberman AP, Pankratz VS, Poon WW, Quinn JF, Saykin AJ, Schneider LS, Smith AG, Sonnen JA, Stern RA, Van Deerlin VM, Van Eldik LJ, Harold D, Russo G, Rubinsztein DC, Bayer A, Tsolaki M, Proitsi P, Fox NC, Hampel H, Owen MJ, Mead S, Passmore P, Morgan K, Nöthen MM, Rossor M, Lupton MK, Hoffmann P, Kornhuber J, Lawlor B, McQuillin A, Al-Chalabi A, Bis JC, Ruiz A, Boada M, Seshadri S, Beiser A, Rice K, van der Lee SJ, De Jager PL, Geschwind DH, Riemenschneider M, Riedel-Heller S, Rotter JI, Ransmayr G, Hyman BT, Cruchaga C, Alegret M, Winsvold B, Palta P, Farh KH, Cuenca-Leon E, Furlotte N, Kurth T, Ligthart L, Terwindt GM, Freilinger T, Ran C, Gordon SD, Borck G, Adams HHH, Lehtimäki T, Wedenoja J, Buring JE, Schürks M, Hrafnsdottir M, Hottenga JJ, Penninx B, Artto V, Kaunisto M, Vepsäläinen S, Martin NG, Montgomery GW, Kurki MI, Hämäläinen E, Huang H, Huang J, Sandor C, Webber C, Muller-Myhsok B, Schreiber S, Salomaa V, Loehrer E, Göbel H, Macaya A, Pozo-Rosich P, Hansen T, Werge T, Kaprio J, Metspalu A, Kubisch C, Ferrari MD, Belin AC, van den Maagdenberg AMJM, Zwart JA, Boomsma D, Eriksson N, Olesen J, Chasman DI, Nyholt DR, Avbersek A, Baum L, Berkovic S, Bradfield J, Buono RJ, Catarino CB, Cossette P, De Jonghe P, Depondt C, Dlugos D, Ferraro TN, French J, Hjalgrim H, Jamnadas-Khoda J, Kälviäinen R, Kunz WS, Lerche H, Leu C, Lindhout D, Lo W, Lowenstein D, McCormack M, Møller RS, Molloy A, Ng PW, Oliver K, Privitera M, Radtke R, Ruppert AK, Sander T, Schachter S, Schankin C, Scheffer I, Schoch S, Sisodiya SM, Smith P, Sperling M, Striano P, Surges R, Thomas GN, Visscher F, Whelan CD, Zara F, Heinzen EL, Marson A, Becker F, Stroink H, Zimprich F, Gasser T, Gibbs R, Heutink P, Martinez M, Morris HR, Sharma M, Ryten M, Mok KY, Pulit S, Bevan S, Holliday E, Attia J, Battey T, Boncoraglio G, Thijs V, Chen WM, Mitchell B, Rothwell P, Sharma P, Sudlow C, Vicente A, Markus H, Kourkoulis C, Pera J, Raffeld M, Silliman S, Boraska Perica V, Thornton LM, Huckins LM, William Rayner N, Lewis CM, Gratacos M, Rybakowski F, Keski-Rahkonen A, Raevuori A, Hudson JI, Reichborn-Kjennerud T, Monteleone P, Karwautz A, Mannik K, Baker JH, O'Toole JK, Trace SE, Davis OSP, Helder SG, Ehrlich S, Herpertz-Dahlmann B, Danner UN, van Elburg AA, Clementi M, Forzan M, Docampo E, Lissowska J, Hauser J, Tortorella A, Maj M, Gonidakis F, Tziouvas K, Papezova H, Yilmaz Z, Wagner G, Cohen-Woods S, Herms S, Julià A, Rabionet R, Dick DM, Ripatti S, Andreassen OA, Espeseth T, Lundervold AJ, Steen VM, Pinto D, Scherer SW, Aschauer H, Schosser A, Alfredsson L, Padyukov L, Halmi KA, Mitchell J, Strober M, Bergen AW, Kaye W, Szatkiewicz JP, Cormand B, Ramos-Quiroga JA, Sánchez-Mora C, Ribasés M, Casas M, Hervas A, Arranz MJ, Haavik J, Zayats T, Johansson S, Williams N, Dempfle A, Rothenberger A, Kuntsi J, Oades RD, Banaschewski T, Franke B, Buitelaar JK, Arias Vasquez A, Doyle AE, Reif A, Lesch KP, Freitag C, Rivero O, Palmason H, Romanos M, Langley K, Rietschel M, Witt SH, Dalsgaard S, Børglum AD, Waldman I, Wilmot B, Molly N, Bau CHD, Crosbie J, Schachar R, Loo SK, McGough JJ, Grevet EH, Medland SE, Robinson E, Weiss LA, Bacchelli E, Bailey A, Bal V, Battaglia A, Betancur C, Bolton P, Cantor R, Celestino-Soper P, Dawson G, De Rubeis S, Duque F, Green A, Klauck SM, Leboyer M, Levitt P, Maestrini E, Mane S, De-Luca DM, Parr J, Regan R, Reichenberg A, Sandin S, Vorstman J, Wassink T, Wijsman E, Cook E, Santangelo S, Delorme R, Rogé B, Magalhaes T, Arking D, Schulze TG, Thompson RC, Strohmaier J, Matthews K, Melle I, Morris D, Blackwood D, McIntosh A, Bergen SE, Schalling M, Jamain S, Maaser A, Fischer SB, Reinbold CS, Fullerton JM, Guzman-Parra J, Mayoral F, Schofield PR, Cichon S, Mühleisen TW, Degenhardt F, Schumacher J, Bauer M, Mitchell PB, Gershon ES, Rice J, Potash JB, Zandi PP, Craddock N, Ferrier IN, Alda M, Rouleau GA, Turecki G, Ophoff R, Pato C, Anjorin A, Stahl E, Leber M, Czerski PM, Cruceanu C, Jones IR, Posthuma D, Andlauer TFM, Forstner AJ, Streit F, Baune BT, Air T, Sinnamon G, Wray NR, MacIntyre DJ, Porteous D, Homuth G, Rivera M, Grove J, Middeldorp CM, Hickie I, Pergadia M, Mehta D, Smit JH, Jansen R, de Geus E, Dunn E, Li QS, Nauck M, Schoevers RA, Beekman AT, Knowles JA, Viktorin A, Arnold P, Barr CL, Bedoya-Berrio G, Bienvenu OJ, Brentani H, Burton C, Camarena B, Cappi C, Cath D, Cavallini M, Cusi D, Darrow S, Denys D, Derks EM, Dietrich A, Fernandez T, Figee M, Freimer N, Gerber G, Grados M, Greenberg E, Hanna GL, Hartmann A, Hirschtritt ME, Hoekstra PJ, Huang A, Huyser C, Illmann C, Jenike M, Kuperman S, Leventhal B, Lochner C, Lyon GJ, Macciardi F, Madruga-Garrido M, Malaty IA, Maras A, McGrath L, Miguel EC, Mir P, Nestadt G, Nicolini H, Okun MS, Pakstis A, Paschou P, Piacentini J, Pittenger C, Plessen K, Ramensky V, Ramos EM, Reus V, Richter MA, Riddle MA, Robertson MM, Roessner V, Rosário M, Samuels JF, Sandor P, Stein DJ, Tsetsos F, Van Nieuwerburgh F, Weatherall S, Wendland JR, Wolanczyk T, Worbe Y, Zai G, Goes FS, McLaughlin N, Nestadt PS, Grabe HJ, Depienne C, Konkashbaev A, Lanzagorta N, Valencia-Duarte A, Bramon E, Buccola N, Cahn W, Cairns M, Chong SA, Cohen D, Crespo-Facorro B, Crowley J, Davidson M, DeLisi L, Dinan T, Donohoe G, Drapeau E, Duan J, Haan L, Hougaard D, Karachanak-Yankova S, Khrunin A, Klovins J, Kučinskas V, Lee Chee Keong J, Limborska S, Loughland C, Lönnqvist J, Maher B, Mattheisen M, McDonald C, Murphy KC, Nenadic I, van Os J, Pantelis C, Pato M, Petryshen T, Quested D, Roussos P, Sanders AR, Schall U, Schwab SG, Sim K, So HC, Stögmann E, Subramaniam M, Toncheva D, Waddington J, Walters J, Weiser M, Cheng W, Cloninger R, Curtis D, Gejman PV, Henskens F, Mattingsdal M, Oh SY, Scott R, Webb B, Breen G, Churchhouse C, Bulik CM, Daly M, Dichgans M, Faraone SV, Guerreiro R, Holmans P, Kendler KS, Koeleman B, Mathews CA, Price A, Scharf J, Sklar P, Williams J, Wood NW, Cotsapas C, Palotie A, Smoller JW, Sullivan P, Rosand J, Corvin A, Neale BM, Schott JM, Anney R, Elia J, Grigoroiu-Serbanescu M, Edenberg HJ, and Murray R
Subjects: Brain Diseases classification, Brain Diseases diagnosis, Genetic Variation, Genome-Wide Association Study, Humans, Mental Disorders classification, Mental Disorders diagnosis, Phenotype, Quantitative Trait, Heritable, Risk Factors, Brain Diseases genetics, Mental Disorders genetics
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Published: 2018
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32. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome.

Author: Greenberg E, Tung ES, Gauvin C, Osiecki L, Yang KG, Curley E, Essa A, Illmann C, Sandor P, Dion Y, Lyon GJ, King RA, Darrow S, Hirschtritt ME, Budman CL, Grados M, Pauls DL, Keuthen NJ, Mathews CA, and Scharf JM
Subjects: Child, Comorbidity, Female, Humans, Male, Prevalence, Surveys and Questionnaires, Tourette Syndrome pathology, Obsessive-Compulsive Disorder etiology, Self-Injurious Behavior etiology, Tourette Syndrome diagnosis, Trichotillomania etiology
Abstract: Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and underlying pathophysiology with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of DSM-5 HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met DSM-5 criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive-compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models.
Published: 2018
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33. Autism Spectrum Symptoms in a Tourette's Disorder Sample.

Author: Darrow SM, Grados M, Sandor P, Hirschtritt ME, Illmann C, Osiecki L, Dion Y, King R, Pauls D, Budman CL, Cath DC, Greenberg E, Lyon GJ, McMahon WM, Lee PC, Delucchi KL, Scharf JM, and Mathews CA
Subjects: Adolescent, Adult, Attention Deficit Disorder with Hyperactivity epidemiology, Autism Spectrum Disorder epidemiology, Child, Comorbidity, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder epidemiology, Tourette Syndrome epidemiology, Young Adult, Attention Deficit Disorder with Hyperactivity physiopathology, Autism Spectrum Disorder physiopathology, Obsessive-Compulsive Disorder physiopathology, Tourette Syndrome physiopathology
Abstract: Objective: Tourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD)., Method: Participants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms., Results: SRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone., Conclusion: Higher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)
Published: 2017
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34. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.

Author: Huang AY, Yu D, Davis LK, Sul JH, Tsetsos F, Ramensky V, Zelaya I, Ramos EM, Osiecki L, Chen JA, McGrath LM, Illmann C, Sandor P, Barr CL, Grados M, Singer HS, Nöthen MM, Hebebrand J, King RA, Dion Y, Rouleau G, Budman CL, Depienne C, Worbe Y, Hartmann A, Müller-Vahl KR, Stuhrmann M, Aschauer H, Stamenkovic M, Schloegelhofer M, Konstantinidis A, Lyon GJ, McMahon WM, Barta C, Tarnok Z, Nagy P, Batterson JR, Rizzo R, Cath DC, Wolanczyk T, Berlin C, Malaty IA, Okun MS, Woods DW, Rees E, Pato CN, Pato MT, Knowles JA, Posthuma D, Pauls DL, Cox NJ, Neale BM, Freimer NB, Paschou P, Mathews CA, Scharf JM, and Coppola G
Subjects: Adolescent, Adult, Calcium-Binding Proteins, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Neural Cell Adhesion Molecules, Odds Ratio, White People genetics, Young Adult, Cell Adhesion Molecules, Neuronal genetics, Contactins genetics, DNA Copy Number Variations, Nerve Tissue Proteins genetics, Tourette Syndrome genetics
Abstract: Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2 × 10 -3 ) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 × 10 -5 ). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6-156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3-45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS., (Copyright © 2017 Elsevier Inc. All rights reserved.)
Published: 2017
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35. Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

Author: Darrow SM, Hirschtritt ME, Davis LK, Illmann C, Osiecki L, Grados M, Sandor P, Dion Y, King R, Pauls D, Budman CL, Cath DC, Greenberg E, Lyon GJ, Yu D, McGrath LM, McMahon WM, Lee PC, Delucchi KL, Scharf JM, and Mathews CA
Subjects: Adolescent, Adult, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity psychology, Child, Child of Impaired Parents, Child, Preschool, Comorbidity, Female, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Male, Middle Aged, Mothers psychology, Multifactorial Inheritance genetics, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder psychology, Phenotype, Risk Assessment, Tourette Syndrome diagnosis, Tourette Syndrome psychology, Young Adult, Attention Deficit Disorder with Hyperactivity genetics, Endophenotypes, Obsessive-Compulsive Disorder genetics, Tourette Syndrome genetics
Abstract: Objective: 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., Method: 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., Results: 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., Conclusions: 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.
Published: 2017
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36. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

Author: Hirschtritt ME, Darrow SM, Illmann C, Osiecki L, Grados M, Sandor P, Dion Y, King RA, Pauls DL, Budman CL, Cath DC, Greenberg E, Lyon GJ, Yu D, McGrath LM, McMahon WM, Lee PC, Delucchi KL, Scharf JM, and Mathews CA
Subjects: Adolescent, Adult, Age of Onset, Attention Deficit Disorder with Hyperactivity epidemiology, Canada epidemiology, Comorbidity, Factor Analysis, Statistical, Female, Humans, Male, Netherlands epidemiology, Obsessive-Compulsive Disorder epidemiology, Phenotype, Tics diagnosis, Tics epidemiology, Tourette Syndrome diagnosis, Tourette Syndrome epidemiology, United Kingdom epidemiology, United States epidemiology, Young Adult, Inhibition, Psychological, Social Behavior, Tics genetics, Tourette Syndrome genetics
Abstract: Objective: To identify heritable symptom-based subtypes of Tourette syndrome (TS)., Methods: Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined., Results: A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18))., Conclusions: Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies., (© 2016 American Academy of Neurology.)
Published: 2016
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37. Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses.

Author: Darrow SM, Illmann C, Gauvin C, Osiecki L, Egan CA, Greenberg E, Eckfield M, Hirschtritt ME, Pauls DL, Batterson JR, Berlin CM, Malaty IA, Woods DW, Scharf JM, and Mathews CA
Subjects: Adolescent, Adult, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit Disorder with Hyperactivity psychology, Child, Comorbidity, Female, Genetic Testing, Humans, Interview, Psychological, Male, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder genetics, Obsessive-Compulsive Disorder psychology, Reproducibility of Results, Tourette Syndrome psychology, Young Adult, Internet, Mass Screening, Phenotype, Tourette Syndrome diagnosis, Tourette Syndrome genetics
Abstract: Collecting phenotypic data necessary for genetic analyses of neuropsychiatric disorders is time consuming and costly. Development of web-based phenotype assessments would greatly improve the efficiency and cost-effectiveness of genetic research. However, evaluating the reliability of this approach compared to standard, in-depth clinical interviews is essential. The current study replicates and extends a preliminary report on the utility of a web-based screen for Tourette Syndrome (TS) and common comorbid diagnoses (obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD)). A subset of individuals who completed a web-based phenotyping assessment for a TS genetic study was invited to participate in semi-structured diagnostic clinical interviews. The data from these interviews were used to determine participants' diagnostic status for TS, OCD, and ADHD using best estimate procedures, which then served as the gold standard to compare diagnoses assigned using web-based screen data. The results show high rates of agreement for TS. Kappas for OCD and ADHD diagnoses were also high and together demonstrate the utility of this self-report data in comparison previous diagnoses from clinicians and dimensional assessment methods., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
Published: 2015
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38. Effectiveness of a web-based protocol for the screening and phenotyping of individuals with Tourette syndrome for genetic studies.

Author: Egan CA, Marakovitz SE, O'Rourke JA, Osiecki L, Illmann C, Barton L, McLaughlin E, Proujansky R, Royal J, Cowley H, Rangel-Lugo M, Pauls DL, Scharf JM, and Mathews CA
Subjects: Adolescent, Adult, Age Factors, Attention Deficit Disorder with Hyperactivity genetics, Child, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mental Disorders genetics, Obsessive-Compulsive Disorder genetics, Phenotype, Tourette Syndrome blood, Young Adult, Genetic Testing, Internet, Surveys and Questionnaires, Tourette Syndrome genetics
Abstract: Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13-month period through the membership of the Tourette Syndrome Association (TSA; n = 28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders., (Copyright © 2012 Wiley Periodicals, Inc.)
Published: 2012
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39. The familial association of tourette's disorder and ADHD: the impact of OCD symptoms.

Author: O'Rourke JA, Scharf JM, Platko J, Stewart SE, Illmann C, Geller DA, King RA, Leckman JF, and Pauls DL
Subjects: Age of Onset, Attention Deficit Disorder with Hyperactivity complications, Case-Control Studies, Comorbidity, Disease Susceptibility psychology, Humans, Interview, Psychological, Obsessive-Compulsive Disorder complications, Risk Factors, Tourette Syndrome complications, Attention Deficit Disorder with Hyperactivity psychology, Family psychology, Obsessive-Compulsive Disorder psychology, Psychiatric Status Rating Scales, Tourette Syndrome psychology
Abstract: Tourette's disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM-IV ADHD and TD. Direct interview diagnostic data from a case-control study of 692 relatives of 75 comorbid TD and ADHD (TD + ADHD), 74 TD without ADHD (TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub-clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD + ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands., (Copyright © 2011 Wiley-Liss, Inc.)
Published: 2011
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40. Four-factor structure of obsessive-compulsive disorder symptoms in children, adolescents, and adults.

Author: Stewart SE, Rosario MC, Baer L, Carter AS, Brown TA, Scharf JM, Illmann C, Leckman JF, Sukhodolsky D, Katsovich L, Rasmussen S, Goodman W, Delorme R, Leboyer M, Chabane N, Jenike MA, Geller DA, and Pauls DL
Subjects: Adolescent, Adult, Age Factors, Child, Female, Humans, Male, Models, Statistical, Obsessive-Compulsive Disorder psychology, Psychometrics statistics & numerical data, Reproducibility of Results, Obsessive-Compulsive Disorder diagnosis, Personality Assessment statistics & numerical data
Abstract: Objective: To determine whether the four-factor category-based obsessive-compulsive disorder (OCD) symptom structure from a previous confirmatory factor analysis (CFA) may be appropriately used in child, adolescent, and adult groups. Symptom dimensions are increasingly used as quantitative traits in genetic, neuroimaging, and treatment studies of OCD across all ages. Identification of a category-based OCD symptom dimension structure that is validated for use across child, adolescent, and adult age groups is necessary to guide ongoing translational research., Method: Four OCD samples comprising 356 individuals were divided into child, adolescent, and adult groups. The fit of the only CFA-defined four-factor model was compared across these independent age group samples. Multiple-group CFA using maximum likelihood estimation assessed adequacy of fit comparing unconstrained and measurement weight-constrained models. The fit of previous exploratory factor analysis-defined three- and five-factor models on adults was also examined using CFA., Results: A four-factor solution provided adequate but imperfect fit across age groups, with comparable indices to the only previous OCD CFA: factor 1 (aggressive/sexual/religious/somatic/checking); factor 2 (symmetry/ordering/counting/repeating); factor 3 (contamination/cleaning), and factor 4 (hoarding). Models in which factor loadings were constrained and unconstrained across the three age groups yielded comparable model fit. Factors were highly correlated and were not mutually exclusive. The four-factor solution provided an improved fit to both three- and five-factor solutions using CFA across the three age groups., Conclusions: A four-factor, CFA-defined, category-based model of OCD symptom dimensions is adequate for use in children, adolescents, and adult age groups. The factor structure of this multiple age group sample has limitations and is imperfect, but current findings support the comparability of the defined latent OCD dimensions across age groups. Further work is needed to optimize a comprehensive symptom dimension model reflecting clinical heterogeneity for use in emergent translational studies.
Published: 2008
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41. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder.

Author: Stewart SE, Fagerness JA, Platko J, Smoller JW, Scharf JM, Illmann C, Jenike E, Chabane N, Leboyer M, Delorme R, Jenike MA, and Pauls DL
Subjects: Adolescent, Age Distribution, Age of Onset, Child, Chromosome Mapping, Female, Gene Frequency, Genetic Predisposition to Disease genetics, Genotype, Haplotypes genetics, Humans, Linkage Disequilibrium genetics, Male, Obsessive-Compulsive Disorder diagnosis, Sex Distribution, Excitatory Amino Acid Transporter 3 genetics, Obsessive-Compulsive Disorder genetics, Polymorphism, Single Nucleotide genetics
Abstract: Context: Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required., Objectives: This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females., Design: Family-based association candidate gene study., Setting: Participants were recruited from tertiary care OCD specialty clinics., Participants: OCD probands and their first degree relatives., Main Outcomes Measures: Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes., Results: Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045)., Conclusions: This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported., (2007 Wiley-Liss, Inc.)
Published: 2007
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42. A controlled family study of attention-deficit/hyperactivity disorder and Tourette's disorder.

Author: Stewart SE, Illmann C, Geller DA, Leckman JF, King R, and Pauls DL
Subjects: Adolescent, Attention Deficit Disorder with Hyperactivity physiopathology, Case-Control Studies, Child, Comorbidity, Female, Humans, Interview, Psychological, Male, Odds Ratio, Phenotype, Tourette Syndrome physiopathology, Attention Deficit Disorder with Hyperactivity genetics, Family, Tourette Syndrome genetics
Abstract: Objective: Although attention-deficit/hyperactivity disorder (ADHD) is frequently comorbid with Tourette's disorder (TD), it is unclear whether they have a common genetic etiology. Familial relationships between DSM-IV ADHD and TD are studied in TD+ADHD, TD-only (TD-ADHD), ADHD-only (ADHD-TD), and control groups., Method: Case-control, direct-interview family study of 692 relatives of 75 TD+ADHD, 74 TD-only, 41 ADHD-only, and 49 control probands collected between 1999 and 2004. Age-corrected prevalence rates, odds ratios, and predictors of TD, ADHD, and OCD among relatives are estimated from blinded best-estimate diagnoses using survival Kaplan-Meier and generalized estimating equation regression analyses., Results: In relatives of the TD-only group, although ADHD exceeded control rates (p=.03), ADHD-TD (p=.51) rates were not increased. In the ADHD-only group, TD was increased (p=.004) but TD-ADHD rates were not increased (p=.18). Comorbid ADHD+TD diagnoses in relatives were elevated in all case groups (p
Published: 2006
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