Phenotype evaluation and genomewide linkage study of clinical variables in schizophrenia

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 156, Issue 8, 2011, Pages 929-940

  Hamshere, Marian L ^a   Holmans, Peter A ^a   McCarthy, Geraldine M ^a   Jones, Lisa A ^a   Murphy, Kieran C ^a   Sanders, Robert D ^a   Gray, Marion Y ^a   Zammit, Stanley ^a   Williams, Nigel M ^a   Norton, Nadine ^a   Williams, Hywel J ^a   McGuffin, Peter ^b   O'Donovan, Michael C ^a   Craddock, Nicholas ^a   Owen, Michael J ^a   Cardno, Alastair G ^c  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

Age at onset; Course; Genetic; Symptom dimensions

Indexed keywords

ADULT; ARTICLE; CHECKLIST; CHROMOSOME 10Q; CHROMOSOME 17Q; CHROMOSOME 20Q; CHROMOSOME 2Q; CHROMOSOME 8P; FEMALE; GENETIC LINKAGE; GENOME ANALYSIS; HUMAN; MAJOR CLINICAL STUDY; MALE; MICROSATELLITE MARKER; ONSET AGE; PHENOTYPE; PRIORITY JOURNAL; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SIBLING; SIMULATION; SYMPTOM; UNITED KINGDOM;

ADULT; AGE OF ONSET; ALLELES; CHROMOSOME MAPPING; FEMALE; GENETIC LINKAGE; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; MALE; MICROSATELLITE REPEATS; MIDDLE AGED; PHENOTYPE; PSYCHOTIC DISORDERS; SCHIZOPHRENIA; SIBLINGS;

EID: 80054868148     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.31240     Document Type: Article

References (89)

1. Allan CL, Cardno AG, Rijsdijk FV, Kalidindi S, Farmer A, Murray RM, McGuffin P. 2009. Twin study of illness history variables in psychosis. Schizophr Res 115: 237-244.
2. Andreasen NC. 1984a. The scale for the assessment of negative symptoms (SANS). Iowa, IA: University of Iowa.
3. Andreasen NC. 1984b. The scale for the assessment of positive symptoms (SAPS). Iowa, IA: University of Iowa.
4. Andreasen NC, Arndt S, Alliger R, Miller D, Flaum M. 1995. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch Gen Psychiatry 52: 341-351.
5. American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Press.
6. Burke JG, Murphy BM, Bray JC, Walsh D, Kendler KS. 1996. Clinical similarities in siblings with schizophrenia. Am J Med Genet Part B 67B: 239-243.
7. Cannon TD, Kaprio J, Lonnqvist J, Huttunen M, Koskenvuo M. 1998. The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Arch Gen Psychiatry 55: 67-74.
8. Cardno AG, Jones LA, Murphy KC, Asherson P, Scott LC, Williams J, Owen MJ, McGuffin P. 1996. Factor analysis of schizophrenic symptoms using the OPCRIT checklist. Schizophr Res 22: 233-239.
9. Cardno AG, Holmans PA, Harvey I, Williams MB, Owen MJ, McGuffin P. 1997. Factor-derived subsyndromes of schizophrenia and familial morbid risks. Schizophr Res 23: 231-238.
10. Cardno AG, Jones LA, Murphy KC, Sanders RD, Asherson P, Owen MJ, McGuffin P. 1998. Sibling pairs with schizophrenia or schizoaffective disorder: Associations of subtypes, symptoms and demographic variables. Psychol Med 28: 815-823.
11. Cardno AG, Jones LA, Murphy KC, Sanders RD, Asherson P, Owen MJ, McGuffin P. 1999. Dimensions of psychosis in affected sibling pairs. Schizophr Bull 25: 841-850.
12. Cardno AG, Holmans PA, Rees MI, Jones LA, McCarthy GM, Hamshere ML, Williams NM, Norton N, Williams HJ, Fenton I, et al. 2001a. A genomewide linkage study of age at onset in schizophrenia. Am J Med Genet Part B 105B: 439-445.
13. Cardno AG, Sham PC, Murray RM, McGuffin P. 2001b. Twin study of symptom dimensions in psychoses. Br J Psychiatry 179: 39-45.
14. Cardno AG, Rijsdijk FV, Sham PC, Murray RM, McGuffin P. 2002. A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry 159: 539-545.
15. Cardno AG, Rijsdijk FV, Murray RM, McGuffin P. 2008. Twin study refining psychotic symptom dimensions as phenotypes for genetic research. Am J Med Genet Part B 147B: 1213-1221.
16. Carroll LS, Williams NM, Moskvina V, Russell E, Norton N, Williams HJ, Peirce T, Georgieva L, Dwyer S, Grozeva D, et al. 2010. Evidence for rare and common genetic risk variants for schizophrenia at protein kinase C, alpha. Mol Psychiatry 15: 1101-1111.
17. Chen PL, Avramopoulos D, Lasseter VK, McGrath JA, Fallin MD, Liang KY, Nestadt G, Feng N, Steel G, Cutting AS, et al. 2009. Fine mapping on chromosome 10q22-q23 implicates Neuregulin 3 in schizophrenia. Am J Hum Genet 84: 21-34.
18. Choi KS, Jeon HO, Lee YS, Jang YL, Kim CH, Ha KS, Shin MH, Hong KS. 2007. Familial association of schizophrenia symptoms retrospectively measured on a lifetime basis. Psychiatr Genet 17: 103-107.
19. Craddock M, Asherson P, Owen MJ, Williams J, McGuffin P, Farmer AE. 1996. Concurrent validity of the OPCRIT diagnostic system. Comparison of OPCRIT diagnoses with consensus best-estimate lifetime diagnoses. Br J Psychiatry 169: 58-63.
20. DeLisi LE, Goldin LR, Maxwell ME, Kazuba DM, Gershon ES. 1987. Clinical features of illness in siblings with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 44: 891-896.
21. DeRosse P, Lencz T, Burdick KE, Siris SG, Kane JM, Malhotra AK. 2008. The genetics of symptom-based phenotypes: Toward a molecular classification of schizophrenia. Schizophr Bull 34: 1047-1053.
22. Dikeos DG, Wickham H, McDonald C, Walshe M, Sigmundsson T, Bramon E, Grech A, Toulopoulou T, Murray R, Sham PC. 2006. Distribution of symptom dimensions across Kraepelinian divisions. Br J Psychiatry 189: 346-353.
23. Escamilla M, Hare E, Dassori AM, Peralta JM, Ontiveros A, Nicolini H, Raventos H, Medina R, Mendoza R, Jerez A, et al. 2009. A schizophrenia gene locus on chromosome 17q21 in a new set of families of Mexican and central American ancestry: Evidence from the NIMH Genetics of schizophrenia in latino populations study. Am J Psychiatry 166: 442-449.
24. Falconer DS, Mackay TFC. 1996. Introduction to quantitative genetics, 4th edition. Harlow, Essex, UK: Longman.
25. Fanous AH, Kendler KS. 2005. Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: Searching for a framework. Mol Psychiatry 10: 6-13.
26. Fanous AH, van den Oord EJ, Riley BP, Aggen SH, Neale MC, O'Neill FA, Walsh D, Kendler KS. 2005. Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia. Am J Psychiatry 162: 1824-1832.
27. Fanous AH, Neale MC, Webb BT, Straub RE, Amdur RL, O'Neill FA, Walsh D, Riley BP, Kendler KS. 2007. A genome-wide scan for modifier loci in schizophrenia. Am J Med Genet Part B 144B: 589-595.
28. Faraone SV, Su J, Tsuang MT. 2004. A genome-wide scan of symptom dimensions in bipolar disorder pedigrees of adult probands. J Affect Disord 82(Suppl 1): S71-S78.
29. Goes FS, Zandi PP, Miao K, McMahon FJ, Steele J, Willour VL, Mackinnon DF, Mondimore FM, Schweizer B, Nurnberger JI Jr, et al. 2007. Mood-incongruent psychotic features in bipolar disorder: Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33. Am J Psychiatry 164: 236-247.
30. Green EK, Raybould R, Macgregor S, Gordon-Smith K, Heron J, Hyde S, Grozeva D, Hamshere M, Williams N, Owen MJ, et al. 2005. Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder. Arch Gen Psychiatry 62: 642-648.
31. Guo G, Wang J. 2002. The mixed or multilevel model for behavior genetic analysis. Behav Genet 32: 37-49.
32. Hamshere ML, Bennett P, Williams N, Segurado R, Cardno A, Norton N, Lambert D, Williams H, Kirov G, Corvin A, et al. 2005a. Genomewide linkage scan in schizoaffective disorder: Significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch Gen Psychiatry 62: 1081-1088.
33. Hamshere ML, Macgregor S, Moskvina V, Nikolov IN, Holmans PA. 2005b. Covariate linkage analysis of GAW14 simulated data incorporating subclinical phenotype, sex, population, parent-of-origin, and interaction. BMC Genet 6(Suppl 1): S45.
34. Hamshere ML, Williams NM, Norton N, Williams H, Cardno AG, Zammit S, Jones LA, Murphy KC, Sanders RD, McCarthy G, et al. 2006. Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes. J Med Genet 43: 563-567.
35. Hamshere ML, Schulze TG, Schumacher J, Corvin A, Owen MJ, Jamra RA, Propping P, Maier W, Orozco Y, Diaz G, Mayoral F, et al. 2009. Mood-incongruent psychosis in bipolar disorder: Conditional linkage analysis shows genome-wide suggestive linkage at 1q32.3, 7p13 and 20q13.31. Bipolar Disord 11: 610-620.
36. Hare E, Glahn DC, Dassori A, Raventos H, Nicolini H, Ontiveros A, Medina R, Mendoza R, Jerez A, Munoz R, et al. 2009. Heritability of age of onset of psychosis in schizophrenia. Am J Med Genet Part B 153B: 298-302.
37. Hedeker D, Gibbons RD. 1996. MIXOR: A computer program for mixed-effects ordinal regression analysis. Comput Methods Programs Biomed 49: 157-176.
38. Holmans PA, Riley B, Pulver AE, Owen MJ, Wildenauer DB, Gejman PV, Mowry BJ, Laurent C, Kendler KS, Nestadt G, et al. 2009. Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms. Mol Psychiatry 14: 786-795.
39. Hwu HG, Wu YC, Lee SF, Yeh LL, Gwo SC, Hsu HC, Chang CJ, Chen WJ. 1997. Concordance of positive and negative symptoms in coaffected sib-pairs with schizophrenia. Am J Med Genet Part B 74B: 1-6.
40. Kendler KS, Tsuang MT, Hays P. 1987. Age at onset in schizophrenia. A familial perspective. Arch Gen Psychiatry 44: 881-890.
41. Kendler KS, Karkowski-Shuman L, O'Neill FA, Straub RE, MacLean CJ, Walsh D. 1997. Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish Study of High-Density Schizophrenia Families: Evidence for possible etiologic heterogeneity. Am J Psychiatry 154: 191-198.
42. Kirov G. 2010. The role of copy number variation in schizophrenia. Expert Rev Neurother 10: 25-32.
43. Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, Richardsson B, Sigurdardottir S, Barnard J, Hallbeck B, Masson G, et al. 2002. A high-resolution recombination map of the human genome. Nat Genet 31: 241-247.
44. Kruglyak L, Lander ES. 1995. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57: 439-454.
45. Lander ES, Green P. 1987. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci USA 84: 2363-2367.
46. Lander E, Kruglyak L. 1995. Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results. Nat Genet 11: 241-247.
47. Leboyer M, Filteau MJ, Jay M, Campion D, d'Amato T, Guilloud-Bataille M, Hillaire D, Feingold J, des Lauriers A, Widlocher D. 1992. Clinical subtypes and age at onset in schizophrenic siblings. Psychiatry Res 41: 107-114.
48. Liddle PF. 1987. The symptoms of chronic schizophrenia. A re-examination of the positive-negative dichotomy. Br J Psychiatry 151: 145-151.
49. Liu IC, Xu R, Blacker DL, Fitzmaurice G, Lyons MJ, Tsuang MT. 2005. The application of a random effects model to censored twin data. Behav Genet 35: 781-789.
50. Loftus J, DeLisi LE, Crow TJ. 1998. Familial associations of subsyndromes of psychosis in affected sibling pairs with schizophrenia and schizoaffective disorder. Psychiatry Res 80: 101-111.
51. Loftus J, Delisi LE, Crow TJ. 2000. Factor structure and familiality of first-rank symptoms in sibling pairs with schizophrenia and schizoaffective disorder. Br J Psychiatry 177: 15-19.
52. McArdle JJ, Prescott CA. 2005. Mixed-effects variance components models for biometric family analyses. Behav Genet 35: 631-652.
53. McGrath JA, Avramopoulos D, Lasseter VK, Wolyniec PS, Fallin MD, Liang KY, Nestadt G, Thornquist MH, Luke JR, Chen PL, et al. 2009. Familiality of novel factorial dimensions of schizophrenia. Arch Gen Psychiatry 66: 591-600.
54. McGuffin P, Farmer A, Harvey I. 1991. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry 48: 764-770.
55. Morar B, Dragovic M, Waters FA, Chandler D, Kalaydjieva L, Jablensky A. 2011. Neuregulin 3 (NRG3) as a susceptibility gene in a schizophrenia subtype with florid delusions and relatively spared cognition. Mol Psychiatry 16: 860-866.
56. Murphy KC, Jones LA, Owen MJ. 1999. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 56: 940-945.
57. Murray V, McKee I, Miller PM, Young D, Muir WJ, Pelosi AJ, Blackwood DH. 2005. Dimensions and classes of psychosis in a population cohort: A four-class, four-dimension model of schizophrenia and affective psychoses. Psychol Med 35: 499-510.
58. Neale M, Cardon L. 1992. Methodology for genetic studies of twins and families. Dordrecht: The Netherlands: Kluwer Academic Publishers.
59. Neale MC, Eaves LJ, Hewitt JK, MacLean CJ, Meyer JM, Kendler KS. 1989. Analyzing the relationship between age at onset and risk to relatives. Am J Hum Genet 45: 226-239.
60. Neale M, Boker S, Xie G, Maes H. 2003. Mx: Statistical modeling: VCU Box 900126. Richmond, VA: Department of Psychiatry.
61. Ng MY, Levinson DF, Faraone SV, Suarez BK, DeLisi LE, Arinami T, Riley B, Paunio T, Pulver AE, Irmansyah, et al. 2009. Meta-analysis of 32 genome-wide linkage studies of schizophrenia. Mol Psychiatry 14: 774-785.
62. Niehaus DJ, Koen L, Laurent C, Muller J, Deleuze JF, Mallet J, Seller C, Jordaan E, Emsley R. 2005. Positive and negative symptoms in affected sib pairs with schizophrenia: Implications for genetic studies in an African Xhosa sample. Schizophr Res 79: 239-249.
63. O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L, et al. 2008. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 40: 1053-1055.
64. Peralta V, Cuesta MJ, Farre C. 1997. Factor structure of symptoms in functional psychoses. Biol Psychiatry 42: 806-815.
65. Ratakonda S, Gorman JM, Yale SA, Amador XF. 1998. Characterization of psychotic conditions. Use of the domains of psychopathology model. Arch Gen Psychiatry 55: 75-81.
66. Rice JP. 1997. The role of meta-analysis in linkage studies of complex traits. Am J Med Genet 74: 112-114.
67. Rice JP. 2001. Diagnosis as a covariate in sib-pair linkage analysis. Am J Med Genet 105: 55-56.
68. Rietkerk T, Boks MP, Sommer IE, Liddle PF, Ophoff RA, Kahn RS. 2008. The genetics of symptom dimensions of schizophrenia: Review and meta-analysis. Schizophr Res 102: 197-205.
69. Rijsdijk FV, Gottesman II, McGuffin P, Cardno AG. 2011. Heritability estimates for psychotic symptom dimensions in twins with psychotic disorders. Am J Med Genet Part B 156B: 89-98.
70. Riley B, Thiselton D, Maher BS, Bigdeli T, Wormley B, McMichael GO, Fanous AH, Vladimirov V, O'Neill FA, Walsh D, et al. 2010. Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample. Mol Psychiatry 15: 29-37.
71. Risch N. 1990. Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am J Hum Genet 46: 242-253.
72. Rosa A, Peralta V, Papiol S, Cuesta MJ, Serrano F, Martínez-Larrea A, Fañanás L. 2004. Interleukin-1beta (IL-1beta) gene and increased risk for the depressive symptom-dimension in schizophrenia spectrum disorders. Am J Med Genet Part B 124B: 10-14.
73. Ross DE, Kirkpatrick B, Karkowski LM, Straub RE, MacLean CJ, O'Neill FA, Compton AD, Murphy B, Walsh D, Kendler KS. 2000. Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families. Am J Psychiatry 157: 1071-1076.
74. Schulze TG, Hedeker D, Zandi P, Rietschel M, McMahon FJ. 2006. What is familial about familial bipolar disorder?: Resemblance among relatives across a broad spectrum of phenotypic characteristics. Arch Gen Psychiatry 63: 1368-1376.
75. Serretti A, Macciardi F, Smeraldi E. 1998. Dopamine receptor D2 Ser/Cys311 variant associated with disorganized symptomatology of schizophrenia. Schizophr Res 34: 207-210.
76. Serretti A, Rietschel M, Lattuada E, Krauss H, Schulze TG, Muller DJ, Maier W, Smeraldi E. 2001. Major psychoses symptomatology: Factor analysis of 2241 psychotic subjects. Eur Arch Psychiatry Clin Neurosci 251: 193-198.
77. Sham PC, Jones P, Russell A, Gilvarry K, Bebbington P, Lewis S, Toone B, Murray R. 1994. Age at onset, sex, and familial psychiatric morbidity in schizophrenia. Camberwell Collaborative Psychosis Study. Br J Psychiatry 165: 466-473.
78. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, et al. 2002. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71: 877-892.
79. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, et al. 2008. Large recurrent microdeletions associated with schizophrenia. Nature 455: 232-236.
80. Steinberg S, Mors O, Borglum AD, Gustafsson O, Werge T, Mortensen PB, Andreassen OA, Sigurdsson E, Thorgeirsson TE, Bottcher Y, et al. 2011. Expanding the range of ZNF804A variants conferring risk of psychosis. Mol Psychiatry 16: 59-66.
81. Suvisaari JM, Haukka J, Tanskanen A, Lonnqvist JK. 1998. Age at onset and outcome in schizophrenia are related to the degree of familial loading. Br J Psychiatry 173: 494-500.
82. Toomey R, Kremen WS, Simpson JC, Samson JA, Seidman LJ, Lyons MJ, Faraone SV, Tsuang MT. 1997. Revisiting the factor structure for positive and negative symptoms: Evidence from a large heterogeneous group of psychiatric patients. Am J Psychiatry 154: 371-377.
83. Vassos E, Sham PC, Cai G, Deng H, Liu X, Sun X, Zhao J, Murray RM, Collier DA, Li T. 2008. Correlation and familial aggregation of dimensions of psychosis in affected sibling pairs from China. Br J Psychiatry 193: 305-310.
84. Wickham H, Walsh C, Asherson P, Taylor C, Sigmundson T, Gill M, Owen MJ, McGuffin P, Murray R, Sham P. 2001. Familiality of symptom dimensions in schizophrenia. Schizophr Res 47: 223-232.
85. Wilcox MA, Faraone SV, Su J, Van Eerdewegh P, Tsuang MT. 2002. Genome scan of three quantitative traits in schizophrenia pedigrees. Biol Psychiatry 52: 847-854.
86. Williams NM, Norton N, Williams H, Ekholm B, Hamshere ML, Lindblom Y, Chowdari KV, Cardno AG, Zammit S, Jones LA, et al. 2003. A systematic genomewide linkage study in 353 sib pairs with schizophrenia. Am J Hum Genet 73: 1355-1367.
87. Williams HJ, Norton N, Dwyer S, Moskvina V, Nikolov I, Carroll L, Georgieva L, Williams NM, Morris DW, Quinn EM, et al. 2011. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. Mol Psychiatry 16: 429-441.
88. Wing JK, Babor T, Brugha T, Burke J, Cooper JE, Giel R, Jablenski A, Regier D, Sartorius N. 1990. SCAN. Schedules for clinical assessment in neuropsychiatry. Arch Gen Psychiatry 47: 589-593.
89. Zhang R, Lu SM, Qiu C, Liu XG, Gao CG, Guo TW, Valenzuela RK, Deng HW, Ma J. 2011. Population-based and family-based association studies of ZNF804A locus and schizophrenia. Mol Psychiatry 16: 360-361.