Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

PLoS Genetics

Volumn 9, Issue 10, 2013, Pages

  Davis, Lea K ^a   Yu, Dongmei ^b,c   Keenan, Clare L ^a   Gamazon, Eric R ^a   Konkashbaev, Anuar I ^a   Derks, Eske M ^d   Neale, Benjamin M ^b,c   Yang, Jian ^e   Lee, S Hong ^e   Evans, Patrick ^a   Barr, Cathy L ^f,g   Bellodi, Laura ^h   Benarroch, Fortu ⁱ   Berrio, Gabriel Bedoya ^j   Bienvenu, Oscar J ^k   Bloch, Michael H ^l,m   Blom, Rianne M ^d   Bruun, Ruth D ^n,o   Budman, Cathy L ^p,q   Camarena, Beatriz ^r   Campbell, Desmond ^s,t   Cappi, Carolina ^u   Cardona Silgado, Julio C ^j   Cath, Danielle C ^v,w,x   Cavallini, Maria C ^y   Chavira, Denise A ^z,aa   Chouinard, Sylvain ^ab   Conti, David V ^ac   Cook, Edwin H ^ad   Coric, Vladimir ^l   Cullen, Bernadette A ^k   Deforce, Dieter ^ae   Delorme, Richard ^af,ag,ah   Dion, Yves ^ab   Edlund, Christopher K ^ac   Egberts, Karin ^ai   Falkai, Peter ^aj   Fernandez, Thomas V ^l,m   Gallagher, Patience J ^b   Garrido, Helena ^ak   Geller, Daniel ^b   Girard, Simon L ^ab   Grabe, Hans J ^al   Grados, Marco A ^k   Greenberg, Benjamin D ^am   Gross Tsur, Varda ^an   Haddad, Stephen ^b   Heiman, Gary A ^ao   Hemmings, Sian M J ^ap   Hounie, Ana G ^aq   Illmann, Cornelia ^b   Jankovic, Joseph ^ar   Jenike, Michael A ^b   Kennedy, James L ^as,at   King, Robert A ^m   Kremeyer, Barbara ^s   Kurlan, Roger ^au   Lanzagorta, Nuria ^av   Leboyer, Marion ^ag,ah,aw   Leckman, James F ^m   Lennertz, Leonhard ^ax   Liu, Chunyu ^ad   Lochner, Christine ^ap   Lowe, Thomas L ^ay   Macciardi, Fabio ^az   McCracken, James T ^az   McGrath, Lauren M ^b   Mesa Restrepo, Sandra C ^j   Moessner, Rainald ^ax   Morgan, Jubel ^ba   Muller, Heike ^s   Murphy, Dennis L ^bb   Naarden, Allan L ^bc   Ochoa, William Cornejo ^j   Ophoff, Roel A ^bd,be   Osiecki, Lisa ^b   Pakstis, Andrew J ^l   Pato, Michele T ^ac   Pato, Carlos N ^ac   Piacentini, John ^bf   Pittenger, Christopher ^m   Pollak, Yehuda ^an   Rauch, Scott L ^bg   Renner, Tobias J ^ai   Reus, Victor I ^ay   Richter, Margaret A ^at,bh   Riddle, Mark A ^k   Robertson, Mary M ^s,bi   Romero, Roxana ^bj   Rosàrio, Maria C ^bk   Rosenberg, David ^bl   Rouleau, Guy A ^bm   Ruhrmann, Stephan ^bn   Ruiz Linares, Andres ^s   Sampaio, Aline S ^aq,bo   Samuels, Jack ^k   Sandor, Paul ^at   Sheppard, Brooke ^ay   Singer, Harvey S ^k   Smit, Jan H ^v   Stein, Dan J ^bp   Strengman, E ^bq   Tischfield, Jay A ^ao   Valencia Duarte, Ana V ^j   Vallada, Homero ^u   Van Nieuwerburgh, Filip ^ae   Veenstra VanderWeele, Jeremy ^br   Walitza, Susanne ^ai,bs   Wang, Ying ^k   Wendland, Jens R ^bb   Westenberg, Herman G M ^bt   Shugart, Yin Yao ^bb   Miguel, Euripedes C ^u   McMahon, William ^bu   Wagner, Michael ^ax   Nicolini, Humberto ^bv   Posthuma, Danielle ^v,bw,bx   Hanna, Gregory L ^by   Heutink, Peter ^v,bz   Denys, Damiaan ^d,bt   Arnold, Paul D ^g,at   Oostra, Ben A ^bx   Nestadt, Gerald ^k   Freimer, Nelson B ^be   Pauls, David L ^b   Wray, Naomi R ^e   Stewart, S Evelyn ^b,ca   Mathews, Carol A ^ay   Knowles, James A ^ac   Cox, Nancy J ^a   Scharf, Jeremiah M ^b,c,cb   more..

^a UNIVERSITY OF CHICAGO   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d UNIVERSITY OF AMSTERDAM   (Netherlands)

^e UNIVERSITY OF QUEENSLAND   (Australia)

^f UNIVERSITY HEALTH NETWORK   (Canada)

^g HOSPITAL FOR SICK CHILDREN   (Canada)

^h VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

ⁱ HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^j UNIVERSIDAD DE ANTIOQUIA   (Colombia)

^k JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^l YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^m YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁿ LONG ISLAND JEWISH MEDICAL CENTER   (United States)

^o NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^p New York University Medical Center ^*  (United States)

^q DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

^r INSTITUTO NACIONAL DE PSIQUIATRÍA RAMÓN DE LA FUENTE MUÑIZ   (Mexico)

^s UNIVERSITY COLLEGE LONDON   (United Kingdom)

^t UNIVERSITY OF HONG KONG   (Hong Kong)

^u UNIVERSITY OF SÃO PAULO   (Brazil)

^v VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^w UTRECHT UNIVERSITY   (Netherlands)

^x Altrecht Academic Anxiety Center   (Netherlands)

^y SAN RAFFAELE HOSPITAL   (Italy)

^z UNIVERSITY OF CALIFORNIA   (United States)

^aa UNIVERSITY OF CALIFORNIA   (United States)

^ab UNIVERSITÉ DE MONTRÉAL   (Canada)

^ac UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^ad UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^ae GHENT UNIVERSITY   (Belgium)

^af INSTITUT PASTEUR   (France)

^ag FONDATION FONDAMENTAL   (France)

^ah HÔPITAL ROBERT DEBRÉ   (France)

^ai UNIVERSITY OF WÜRZBURG   (Germany)

^aj UNIVERSITY OF MUNICH   (Germany)

^ak Clinica Herrera Amighetti   (Costa Rica)

^al UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^am BUTLER HOSPITAL   (United States)

^an SHAARE ZEDEK MEDICAL CENTER   (Israel)

^ao Life Sciences Building Rutgers University   (United States)

^ap STELLENBOSCH UNIVERSITY   (South Africa)

^aq Shaare Zedek Medical Center ^*  (Brazil)

^ar BAYLOR COLLEGE OF MEDICINE   (United States)

^as CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^at UNIVERSITY OF TORONTO   (Canada)

^au OVERLOOK HOSPITAL   (United States)

^av Grupo Medico Carracci   (Mexico)

^aw INSERM U955   (France)

^ax UNIVERSITY OF BONN   (Germany)

^ay UNIVERSITY OF CALIFORNIA   (United States)

^az UNIVERSITY OF CALIFORNIA   (United States)

^ba UNIVERSITY OF UTAH   (United States)

^bb NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^bc MEDICAL CITY DALLAS HOSPITAL   (United States)

^bd UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^be UNIVERSITY OF CALIFORNIA   (United States)

^bf UNIVERSITY OF CALIFORNIA   (United States)

^bg MCLEAN HOSPITAL   (United States)

^bh SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^bi ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^bj HOSPITAL NACIONAL DE NIÑOS   (Costa Rica)

^bk FEDERAL UNIVERSITY OF SÃO PAULO   (Brazil)

^bl WAYNE STATE UNIVERSITY   (United States)

^bm MCGILL UNIVERSITY   (Canada)

^bn UNIVERSITY OF COLOGNE   (Germany)

^bo FEDERAL UNIVERSITY OF BAHIA   (Brazil)

^bp UNIVERSITY OF CAPE TOWN   (South Africa)

^bq UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^br VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^bs UNIVERSITY OF ZURICH   (Switzerland)

^bt NETHERLANDS INSTITUTE FOR NEUROSCIENCE   (Netherlands)

^bu UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^bv INSTITUTO NACIONAL DE MEDICINA GENÓMICA   (Mexico)

^bw VU UNIVERSITY AMSTERDAM   (Netherlands)

^bx ERASMUS MEDICAL CENTER   (Netherlands)

^by UNIVERSITY OF MICHIGAN   (United States)

^bz GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^ca UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^cb BRIGHAM AND WOMEN S HOSPITAL   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADOLESCENT; ADULT; ARTICLE; BRAIN MAPPING; CEREBELLUM; CHROMOSOME SIZE; CONTROLLED STUDY; CORRELATION ANALYSIS; DISEASE ASSOCIATION; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC VARIABILITY; GILLES DE LA TOURETTE SYNDROME; HERITABILITY; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; NEUROIMAGING; NUCLEOTIDE SEQUENCE; OBSESSIVE COMPULSIVE DISORDER; ONSET AGE; PARIETAL CORTEX; PLEIOTROPY; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM; GENETICS; PATHOLOGY; PHENOTYPE; QUANTITATIVE TRAIT;

GENE FREQUENCY; GENOME-WIDE ASSOCIATION STUDY; HUMANS; OBSESSIVE-COMPULSIVE DISORDER; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT, HERITABLE; TOURETTE SYNDROME;

EID: 84887265151     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1003864     Document Type: Article

References (61)

1. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747-753.
2. Zuk O, Hechter E, Sunyaev SR, Lander ES, (2012) The mystery of missing heritability: Genetic interactions create phantom heritability. Proc Natl Acad Sci U S A 109: 1193-1198.
3. Eichler EE, Flint J, Gibson G, Kong A, Leal SM, et al. (2010) Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 11: 446-450.
4. Lee SH, Wray NR, Goddard ME, Visscher PM, (2011) Estimating missing heritability for disease from genome-wide association studies. Am J Hum Genet 88: 294-305.
5. Yang J, Lee SH, Goddard ME, Visscher PM, (2011) GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 88: 76-82.
6. Klei L, Sanders SJ, Murtha MT, Hus V, Lowe JK, et al. (2012) Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism 3: 9.
7. Keller MF, Saad M, Bras J, Bettella F, Nicolaou N, et al. (2012) Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease. Hum Mol Genet 21: 4996-5009.
8. Lee SH, Yang J, Goddard ME, Visscher PM, Wray NR, (2012) Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood. Bioinformatics 28: 2540-2542.
9. Miguel EC, do Rosario-Campos MC, Prado HS, do Valle R, Rauch SL, et al. (2000) Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder. J Clin Psychiatry 61: 150-156; quiz 157.
10. Miguel EC, Baer L, Coffey BJ, Rauch SL, Savage CR, et al. (1997) Phenomenological differences appearing with repetitive behaviours in obsessive-compulsive disorder and Gilles de la Tourette's syndrome. Br J Psychiatry 170: 140-145.
11. Ferrao YA, Miguel E, Stein DJ, (2009) Tourette's syndrome, trichotillomania, and obsessive-compulsive disorder: how closely are they related? Psychiatry Res 170: 32-42.
12. Graybiel AM, (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31: 359-387.
13. Harrison BJ, Pujol J, Cardoner N, Deus J, Alonso P, et al. (2013) Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder. Biol Psychiatry 73: 321-328.
14. Wang L, Lee DY, Bailey E, Hartlein JM, Gado MH, et al. (2007) Validity of large-deformation high dimensional brain mapping of the basal ganglia in adults with Tourette syndrome. Psychiatry Res 154: 181-190.
15. Pauls DL, (1992) The genetics of obsessive compulsive disorder and Gilles de la Tourette's syndrome. Psychiatr Clin North Am 15: 759-766.
16. van Grootheest DS, Cath DC, Beekman AT, Boomsma DI, (2005) Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet 8: 450-458.
17. Mathews CA, Greenwood T, Wessel J, Azzam A, Garrido H, et al. (2008) Evidence for a heritable unidimensional symptom factor underlying obsessionality. Am J Med Genet B Neuropsychiatr Genet 147B: 676-685.
18. Grados MA, Mathews CA, (2008) Latent class analysis of gilles de la tourette syndrome using comorbidities: clinical and genetic implications. Biol Psychiatry 64: 219-225.
19. Katerberg H, Delucchi KL, Stewart SE, Lochner C, Denys DA, et al. (2010) Symptom dimensions in OCD: item-level factor analysis and heritability estimates. Behav Genet 40: 505-517.
20. van Grootheest DS, Cath D, Hottenga JJ, Beekman AT, Boomsma DI, (2009) Genetic factors underlie stability of obsessive-compulsive symptoms. Twin Res Hum Genet 12: 411-419.
21. Kidd KK, Heimbuch RC, Records MA, Oehlert G, Webster RL, (1980) Familial stuttering patterns are not related to one measure of severity. J Speech Hear Res 23: 539-545.
22. Kidd KK, Prusoff BA, Cohen DJ, (1980) Familial pattern of Gilles de la Tourette syndrome. Arch Gen Psychiatry 37: 1336-1339.
23. Kano Y, Ohta M, Nagai Y, Pauls DL, Leckman JF, (2001) A family study of Tourette syndrome in Japan. Am J Med Genet 105: 414-421.
24. Pauls DL, Raymond CL, Stevenson JM, Leckman JF, (1991) A family study of Gilles de la Tourette syndrome. Am J Hum Genet 48: 154-163.
25. Hebebrand J, Klug B, Fimmers R, Seuchter SA, Wettke-Schafer R, et al. (1997) Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome. J Psychiatr Res 31: 519-530.
26. Price RA, Kidd KK, Cohen DJ, Pauls DL, Leckman JF, (1985) A twin study of Tourette syndrome. Arch Gen Psychiatry 42: 815-820.
27. Bolton D, Rijsdijk F, O'Connor TG, Perrin S, Eley TC, (2007) Obsessive-compulsive disorder, tics and anxiety in 6-year-old twins. Psychol Med 37: 39-48.
28. Lichtenstein P, Carlstrom E, Rastam M, Gillberg C, Anckarsater H, (2010) The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood. Am J Psychiatry 167: 1357-1363.
29. O'Rourke JA, Scharf JM, Yu D, Pauls DL, (2009) The genetics of Tourette syndrome: a review. J Psychosom Res 67: 533-545.
30. Scharf JM, Yu D, Mathews CA, Neale BM, Stewart SE, et al. (2012) Genome-wide association study of Tourette's syndrome. Mol Psychiatry 18 (6) (): 721-8.
31. Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, et al. (2012) Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry 18 (7) (): 788-98.
32. Patterson N, Price AL, Reich D, (2006) Population structure and eigenanalysis. PLoS Genet 2: e190.
33. Karno M, Golding JM, Sorenson SB, Burnam MA, (1988) The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry 45: 1094-1099.
34. Khalifa N, von Knorring AL, (2003) Prevalence of tic disorders and Tourette syndrome in a Swedish school population. Dev Med Child Neurol 45: 315-319.
35. Wang HS, Kuo MF, (2003) Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County. Brain Dev 25 Suppl 1: S29-31.
36. Lanzi G, Zambrino CA, Termine C, Palestra M, Ferrari Ginevra O, et al. (2004) Prevalence of tic disorders among primary school students in the city of Pavia, Italy. Arch Dis Child 89: 45-47.
37. Wang K, Li M, Hakonarson H, (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38: e164.
38. Gamazon ER, Badner JA, Cheng L, Zhang C, Zhang D, et al. (2012) Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants. Mol Psychiatry 18 (3) (): 340-6.
39. Elbein SC, Kern PA, Rasouli N, Yao-Borengasser A, Sharma NK, et al. (2011) Global gene expression profiles of subcutaneous adipose and muscle from glucose-tolerant, insulin-sensitive, and insulin-resistant individuals matched for BMI. Diabetes 60: 1019-1029.
40. Elbein SC, Gamazon ER, Das SK, Rasouli N, Kern PA, et al. (2012) Genetic risk factors for type 2 diabetes: a trans-regulatory genetic architecture? Am J Hum Genet 91: 466-477.
41. Johnson WE, Li C, Rabinovic A, (2007) Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8: 118-127.
42. Leek JT, Storey JD, (2007) Capturing heterogeneity in gene expression studies by surrogate variable analysis. PLoS Genet 3: 1724-1735.
43. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559-575.
44. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR, (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34: 816-834.
45. Li Y, Willer C, Sanna S, Abecasis G, (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10: 387-406.
46. Nestadt G, Samuels J, Riddle M, Bienvenu OJ 3rd, Liang KY, et al. (2000) A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 57: 358-363.
47. Hanna GL, Himle JA, Curtis GC, Gillespie BW, (2005) A family study of obsessive-compulsive disorder with pediatric probands. Am J Med Genet B Neuropsychiatr Genet 134B: 13-19.
48. Lee SH, Harold D, Nyholt DR, Goddard ME, Zondervan KT, et al. (2013) Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis. Hum Mol Genet 22: 832-841.
49. Scharf JM, Pauls D (2007) Genetics of tic disorders. In: D.L. R, M. CJ, R.E. P, R. KB, editors. Principles and Pracitices of Medical Genetics. 5th ed. New York: Elsevier. pp. 2737-2754.
50. Consortium C-DGotPG (2013) Genetic relationships between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45 (9) (): 984-94.
51. Yang J, Manolio TA, Pasquale LR, Boerwinkle E, Caporaso N, et al. (2011) Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 43: 519-525.
52. Shugart YY, Samuels J, Willour VL, Grados MA, Greenberg BD, et al. (2006) Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. Mol Psychiatry 11: 763-770.
53. Ross J, Badner J, Garrido H, Sheppard B, Chavira DA, et al. (2011) Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD. Hum Genet 130: 795-805.
54. Shao Y, Cuccaro ML, Hauser ER, Raiford KL, Menold MM, et al. (2003) Fine mapping of autistic disorder to chromosome 15q11-q13 by use of phenotypic subtypes. Am J Hum Genet 72: 539-548.
55. Delahanty RJ, Kang JQ, Brune CW, Kistner EO, Courchesne E, et al. (2011) Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Mol Psychiatry 16: 86-96.
56. Doornbos M, Sikkema-Raddatz B, Ruijvenkamp CA, Dijkhuizen T, Bijlsma EK, et al. (2009) Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur J Med Genet 52: 108-115.
57. Nestadt G, Wang Y, Grados MA, Riddle MA, Greenberg BD, et al. (2012) Homeobox genes in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 159B: 53-60.
58. Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, et al. (1998) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155: 264-271.
59. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43: 969-976.
60. Gamazon E, Im H, Liu C, Nicolae D, Cox N (2012) The convergence of functional genomics, heritability estimation, and polygenic modeling: Emerging spectrum of alleleic variation in bipolar disorder. arXiv:submit/0682261.
61. Davis LK, Gamazon ER, Kistner-Griffin E, Badner JA, Liu C, et al. (2012) Loci nominally associated with autism from genome-wide analysis show enrichment of brain expression quantitative trait loci but not lymphoblastoid cell line expression quantitative trait loci. Mol Autism 3: 3.