Genetics of schizophrenia: New findings and challenges

Annual Review of Genomics and Human Genetics

Volumn 12, Issue , 2011, Pages 121-144

  Gejman, Pablo V ^a   Sanders, Alan R ^a   Kendler, Kenneth S ^b  

^a NORTHSHORE UNIVERSITY HEALTHSYSTEM   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

CNV; Complex disorders; GWAS; Polygenic; SNP

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; ALPHA SYNUCLEIN; APOLIPOPROTEIN E; AXONIN 1; CATECHOL METHYLTRANSFERASE; DISRUPTED IN SCHIZOPHRENIA 1 PROTEIN; DJ 1 PROTEIN; DOPAMINE 2 RECEPTOR; DYSBINDIN; EPIDERMAL GROWTH FACTOR RECEPTOR 4; FRAGILE X MENTAL RETARDATION PROTEIN; NEU DIFFERENTIATION FACTOR; NEUREXIN; NEUROGRANIN; SEROTONIN 2 RECEPTOR; TRANSMEMBRANE CONDUCTANCE REGULATOR; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2; ZINC FINGER PROTEIN;

ALLELE; ARTICLE; AUTISM; BIPOLAR DISORDER; COPY NUMBER VARIATION; DIZYGOTIC TWINS; ENVIRONMENTAL FACTOR; EXOME; GENE DELETION; GENE EXPRESSION; GENE FREQUENCY; GENE LOCUS; GENE MUTATION; GENE REPLICATION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; HEREDITY; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; MOLECULAR GENETICS; MONOZYGOTIC TWINS; MULTIFACTORIAL INHERITANCE; NEUROPATHOLOGY; PATERNAL AGE; PLEIOTROPY; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM;

ADOPTION; GENETIC PLEIOTROPY; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MENTAL DISORDERS; SCHIZOPHRENIA; TWIN STUDIES AS TOPIC;

EID: 80052765557     PISSN: 15278204     EISSN: 1545293X     Source Type: Book Series    
DOI: 10.1146/annurev-genom-082410-101459     Document Type: Article

References (211)

1. Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, et al. 2008. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat. Genet. 40:827-34 (Pubitemid 351913655)
2. Amer. Psychiatr. Assoc. 1994. Diagnostic and StatisticalManual ofMental Disorders, Fourth Edition (DSMIV). Washington, DC: Amer. Psychiatr. Assoc.
3. Athanasiu L, Mattingsdal M, Kahler AK, Brown A, Gustafsson O, et al. 2010. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J. Psychiatr. Res. 44:748-53
4. Ayroles JF, Carbone MA, Stone EA, Jordan KW, Lyman RF, et al. 2009. Systems genetics of complex traits in Drosophila melanogaster. Nat. Genet. 41:299-307
5. Bach ML, Bach FH, Joo P. 1969. Leukemia-associated antigens in the mixed leukocyte culture test. Science 166:1520-22
6. Ballif BC, Theisen A, Coppinger J, Gowans GC, Hersh JH, et al. 2008. Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication. Mol. Cytogenet. 1:8
7. Bassell GJ, Warren ST. 2008. Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60:201-14
8. Ben-Shachar S, Lanpher B, German JR, Qasaymeh M, Potocki L, et al. 2009. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J. Med. Genet. 46:382-88
9. Berrettini WH. 2000. Are schizophrenic and bipolar disorders related? A review of family and molecular studies. Biol. Psychiatry 48:531-38
10. Birren B, Green ED, Klapholz S, Myers RM, Roskams J. 1998. Genome Analysis: A Laboratory Manual. Vol. 4: Mapping Genomes. Cold Spring Harbor, NY: Cold Spring Harb. Lab.
11. Bittel DC, Kibiryeva N, Butler MG. 2007. Whole genome microarray analysis of gene expression in subjects with fragile X syndrome. Genet. Med. 9:464-72 (Pubitemid 47222139)
12. Blake DJ, Forrest M, Chapman RM, Tinsley CL, O'DonovanMC, Owen MJ. 2010. TCF4, schizophrenia, and Pitt-Hopkins Syndrome. Schizophr. Bull. 36:443-47
13. Brockschmidt A, Todt U, Ryu S, Hoischen A, Landwehr C, et al. 2007. Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. Hum. Mol. Genet. 16:1488-94 (Pubitemid 47055120)
14. Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, et al. 2008. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat. Genet. 40:1466-71
15. Byrne M, Agerbo E, Bennedsen B, Eaton WW, Mortensen PB. 2007. Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study. Schizophr. Res. 97:51-59 (Pubitemid 350088389)
16. 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 (Pubitemid 28069041)
17. Cardno AG, Gottesman I. 2000. Twin studies of schizophrenia: from bow-and-arrow concordances to Star Wars Mx and functional genomics. Am. J. Med. Genet. 97:12-17 (Pubitemid 30257322)
18. Cardno AG, Marshall EJ, Coid B,Macdonald AM, Ribchester TR, et al. 1999. Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch. Gen. Psychiatry 56:162-68 (Pubitemid 29081391)
19. Carroll LS,OwenMJ. 2009. Genetic overlap between autism, schizophrenia and bipolar disorder. Genome Med. 1:102
20. Cascella NG, Schretlen DJ, Sawa A. 2009. Schizophrenia and epilepsy: Is there a shared susceptibility? Neurosci. Res. 63:227-35
21. Ching MS, Shen Y, Tan WH, Jeste SS, Morrow EM, et al. 2010. Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B:937-47
22. Christian SL, Brune CW, Sudi J, Kumar RA, Liu S, et al. 2008. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol. Psychiatry 63:1111-17
23. Cichon S, Craddock N, Daly M, Faraone SV, Gejman PV, et al. 2009. Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am. J. Psychiatry 166:540-56
24. Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M. 2009. Mapping complex disease traits with global gene expression. Nat. Rev. Genet. 10:184-94
25. Corbo RM, Gambina G, Ruggeri M, Scacchi R. 2006. Association of estrogen receptor alpha (ESR1) PvuII and XbaI polymorphisms with sporadic Alzheimer's disease and their effect on apolipoprotein E concentrations. Dement. Geriatr. Cogn. Disord. 22:67-72
26. Corvin A, Craddock N, Sullivan PF. 2010. Genome-wide association studies: a primer. Psychol. Med. 40:1063-77
27. Craddock N, Owen MJ. 2007. Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry 6:84-91
28. Craddock N, Owen MJ. 2010. The Kraepelinian dichotomy: going, going. . .but still not gone. Br. J. Psychiatry 196:92-95
29. Daniels JL, ForssenU,Hultman CM,Cnattingius S, Savitz DA, et al. 2008. Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics 121:e1357-62
30. De Kovel CG, Trucks H, Helbig I, Mefford HC, Baker C, et al. 2009. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 133:23-32
31. Dibbens LM, Mullen S, Helbig I, Mefford HC, Bayly MA, et al. 2009. Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum. Mol. Genet. 18:3626-31
32. Donohoe G, Morris DW, Corvin A. 2010. The psychosis susceptibility gene ZNF804A: associations, functions, and phenotypes. Schizophr. Bull. 36:904-9
33. Drachman DA. 2005. Do we have brain to spare? Neurology 64:2004-5 (Pubitemid 40880984)
34. Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, et al. 2010. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42:295-302
35. Dudbridge F, Gusnanto A. 2008. Estimation of significance thresholds for genomewide association scans. Genet. Epidemiol. 32:227-34 (Pubitemid 351550369)
36. Fisher RA. 1918. On the correlation between relatives on the supposition of Mendelian inheritance. Trans. R. Soc. Edinb. 52:399-433
37. Flora A, Garcia JJ, Thaller C, Zoghbi HY. 2007. The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. Proc. Natl. Acad. Sci. USA 104:15382-87 (Pubitemid 47502926)
38. Franzek E, Beckmann H. 1998. Different genetic background of schizophrenia spectrum psychoses: a twin study. Am. J. Psychiatry 155:76-83 (Pubitemid 28037552)
39. Friedman JI, Vrijenhoek T, Markx S, Janssen IM, van der VlietWA, et al. 2008. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol. Psychiatry 13:261-66 (Pubitemid 351272653)
40. Friedman JM, Baross A, Delaney AD, Ally A, Arbour L, et al. 2006. Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. Am. J. Hum. Genet. 79:500-13 (Pubitemid 44384259)
41. Fuchs J, Tichopad A, Golub Y, Munz M, Schweitzer KJ, et al. 2008. Genetic variability in the SNCA gene influences alpha-synuclein levels in the blood and brain. FASEB J. 22:1327-34 (Pubitemid 351656774)
42. Gard DL. 1991. Organization, nucleation, and acetylation of microtubules in Xenopus laevis oocytes: a study by confocal immunofluorescence microscopy. Dev. Biol. 143:346-62 (Pubitemid 121004660)
43. Gejman PV. 1997. Ernst R̈ udin and Nazi euthanasia: another stain on his career. Am. J. Med. Genet. 74:455-56
44. Gejman PV, Sanders AR, Duan J. 2010. The role of genetics in the etiology of schizophrenia. Psychiatr. Clin. North Am. 33:35-66
45. Gershon ES, DeLisi LE, Hamovit J, Nurnberger JI Jr, Maxwell ME, et al. 1988. A controlled family study of chronic psychoses: schizophrenia and schizoaffective disorder. Arch. Gen. Psychiatry 45:328-36
46. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, et al. 1982. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch. Gen. Psychiatry 39:1157-67 (Pubitemid 12034170)
47. Gibson G, Dworkin I. 2004. Uncovering cryptic genetic variation. Nat. Rev. Genet. 5:681-90 (Pubitemid 39150126)
48. Girard C, Simard M. 2008. Clinical characterization of late-and very late-onset first psychotic episode in psychiatric inpatients. Am. J. Geriatr. Psychiatry 16:478-87
49. Glessner JT, Reilly MP, Kim CE, Takahashi N, Albano A, et al. 2010. Strong synaptic transmission impact by copy number variations in schizophrenia. Proc. Natl. Acad. Sci. USA 107:10584-89
50. Goes FS, Zandi PP, Miao K, McMahon FJ, Steele J, et al. 2007. Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33. Am. J. Psychiatry 164:236-47
51. Goring HH, Curran JE, Johnson MP, Dyer TD, Charlesworth J, et al. 2007. Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nat. Genet. 39:1208-16 (Pubitemid 47482685)
52. Gottesman II, Bertelsen A. 1989. Confirming unexpressed genotypes for schizophrenia: risks in the offspring of Fischer's Danish identical and fraternal discordant twins. Arch. Gen. Psychiatry 46:867-72 (Pubitemid 19259531)
53. Gottesman II, Laursen TM, Bertelsen A,Mortensen PB. 2010. Severemental disorders in offspring with 2 psychiatrically ill parents. Arch. Gen. Psychiatry 67:252-57
54. Gottesman II, Shields J. 1967. A polygenic theory of schizophrenia. Proc.Natl. Acad. Sci. USA 58:199-205
55. Gottesman II, Shields J. 1982. Schizophrenia: The Epigenetic Puzzle. Cambridge: Cambridge Univ. Press
56. Green EK, Grozeva D, Jones I, Jones L, Kirov G, et al. 2010. The bipolar disorder risk allele at CACNA1Calso confers risk of recurrent major depression and of schizophrenia. Mol. Psychiatry 15:1016-22
57. Gulacsi AA, Anderson SA. 2008. Beta-catenin-mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat. Neurosci. 11:1383-91
58. Hannes FD, Sharp AJ, Mefford HC, de Ravel T, Ruivenkamp CA, et al. 2009. Recurrent reciprocal deletions and duplications of 16p13.11: The deletion is a risk factor forMR/MCA while the duplication may be a rare benign variant. J. Med. Genet. 46:223-32
59. Harrison PJ, Weinberger DR. 2005. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry 10:40-68 (Pubitemid 40139588)
60. Hartman JL, Garvik B, Hartwell L. 2001. Principles for the buffering of genetic variation. Science 291:1001-4
61. Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, et al. 2009. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat. Genet. 41:160-62
62. Hermisson J,Wagner GP. 2004. The population genetic theory of hidden variation and genetic robustness. Genetics 168:2271-84 (Pubitemid 40066360)
63. Herold C, Steffens M, Brockschmidt FF, Baur MP, Becker T. 2009. INTERSNP: genome-wide interaction analysis guided by a priori information. Bioinformatics 25:3275-81
64. Heston LL. 1966. Psychiatric disorders in foster home reared children of schizophrenic mothers. Br. J. Psychiatry 112:819-25
65. Higgins J. 1976. Effects of child rearing by schizophrenic mothers: a follow-up. J. Psychiatr. Res. 13:1-9
66. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, et al. 2009. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA 106:9362-67
67. Hoggart CJ, Clark TG, De Iorio M, Whittaker JC, Balding DJ. 2008. Genome-wide significance for dense SNP and resequencing data. Genet. Epidemiol. 32:179-85 (Pubitemid 351288034)
68. Hyde TM,Weinberger DR. 1997. Seizures and schizophrenia. Schizophr. Bull. 23:611-22 (Pubitemid 27485970)
69. Idaghdour Y, Czika W, Shianna KV, Lee SH, Visscher PM, et al. 2010. Geographical genomics of human leukocyte gene expression variation in southern Morocco. Nat. Genet. 42:62-67
70. Ideker T, Bandyopadhyay S. 2010. Integrative systems biology. Nat. Genet. 42(12): poster; http://www.nature.com/ng/extra/sysbio/index.html
71. Ikeda M, Aleksic B, Kinoshita Y, Okochi T, Kawashima K, et al. 2011. Genome-wide association study of schizophrenia in a Japanese population. Biol. Psychiatry 69:472-78
72. Ikeda M, Aleksic B, Kirov G, Kinoshita Y, Yamanouchi Y, et al. 2010. Copy number variation in schizophrenia in the Japanese population. Biol. Psychiatry 67:283-86
73. Ingason A, Rujescu D, Cichon S, Sigurdsson E, Sigmundsson T, et al. 2011. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol. Psychiatry 16:17-25
74. Ingraham LJ, Kety SS. 2000. Adoption studies of schizophrenia. Am. J. Med. Genet. 97:18-22 (Pubitemid 30257323)
75. Int. Schizophr. Consort. 2008. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237-41
76. Ioannidis JP. 2008. Why most discovered true associations are inflated. Epidemiology 19:640-48
77. Irrcher I, AleyasinH, Seifert EL, Hewitt SJ,Chhabra S, et al. 2010. Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum. Mol. Genet. 19:3734-46
78. Itsara A, Cooper GM, Baker C, Girirajan S, Li J, et al. 2009. Population analysis of large copy number variants and hotspots of human genetic disease. Am. J. Hum. Genet. 84:148-61
79. Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CM, Smeets DF, Menzel C, et al. 2008. Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome. Am. J. Med. Genet. A 146A:2053-59
80. Kamin LJ, Goldberger AS. 2002. Twin studies in behavioral research: a skeptical view. Theor. Popul. Biol. 61:83-95 (Pubitemid 38042737)
81. Kathiresan S, Willer CJ, Peloso GM, Demissie S,Musunuru K, et al. 2009. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat. Genet. 41:56-65
82. Kendler KS. 1987. Sporadic versus familial classification given etiologic heterogeneity: I: sensitivity, specificity, and positive and negative predictive value. Genet. Epidemiol. 4:313-30 (Pubitemid 17165060)
83. Kendler KS, Diehl SR. 1993. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr. Bull. 19:261-85 (Pubitemid 23183148)
84. Kendler KS, Gruenberg AM, Kinney DK. 1994. Independent diagnoses of adoptees and relatives as defined by DSM-III in the provincial and national samples of theDanish Adoption Study of Schizophrenia. Arch. Gen. Psychiatry 51:456-68 (Pubitemid 24180492)
85. Kendler KS, Gruenberg AM, Strauss JS. 1981. An independent analysis of the Copenhagen sample of the Danish Adoption Study of Schizophrenia: II: the relationship between schizotypal personality disorder and schizophrenia. Arch. Gen. Psychiatry 38:982-84 (Pubitemid 11061224)
86. Kendler KS, McGuire M, Gruenberg AM, O'Hare A, Spellman M, Walsh D. 1993. The Roscommon Family Study: I: methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch. Gen. Psychiatry 50:527-40 (Pubitemid 23203564)
87. Kendler KS, Neale MC. 2010. Endophenotype: a conceptual analysis. Mol. Psychiatry 15:789-97
88. Kety SS, Rosenthal D,Wender PH, Schulsinger F. 1968. The types and prevalence of mental illness in the biological and adoptive families of adopted schizophrenics. In The Transmission of Schizophrenia., ed. D Rosenthal, SS Kety, pp. 345-62. Oxford, UK: Pergamon
89. Kety SS, RosenthalD,Wender PH, Schulsinger F, Jacobsen B. 1975. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: a preliminary report based upon psychiatric interviews. In Genetic Research in Psychiatry, ed. R Fieve, D Rosenthal, H Brill, pp. 147-65. Baltimore: Johns Hopkins Univ. Press
90. Kety SS, Wender PH, Jacobsen B, Ingraham LJ, Jansson L, et al. 1994. Mental illness in the biological and adoptive relatives of schizophrenic adoptees: replication of the Copenhagen Study in the rest of Denmark. Arch. Gen. Psychiatry 51:442-55 (Pubitemid 24180491)
91. Khoury MJ, Bertram L, Boffetta P, Butterworth AS, Chanock SJ, et al. 2009. Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases. Am. J. Epidemiol. 170:269-79
92. Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, et al. 2008. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82:199-207 (Pubitemid 351735950)
93. Kim S, Jeon BS, Heo C, Im PS, Ahn TB, et al. 2004. Alpha-synuclein induces apoptosis by altered expression in human peripheral lymphocyte in Parkinson's disease. FASEB J. 18:1615-17 (Pubitemid 39561651)
94. Kirov G, Grozeva D, Norton N, Ivanov D, Mantripragada KK, et al. 2009. Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Hum. Mol. Genet. 18:1497-503
95. Kirov G, Gumus D, Chen W, Norton N, Georgieva L, et al. 2008. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum. Mol. Genet. 17:458-65
96. KlaningU,Mortensen PB,Kyvik KO. 1996. Increased occurrence of schizophrenia and other psychiatric illnesses among twins. Br. J. Psychiatry 168:688-92
97. Kleinjan DA, van Heyningen V. 2005. Long-range control of gene expression: emerging mechanisms and disruption in disease. Am. J. Hum. Genet. 76:8-32 (Pubitemid 40023762)
98. Konstantareas MM, Hewitt T. 2001. Autistic disorder and schizophrenia: diagnostic overlaps. J. Autism Dev. Disord. 31:19-28
99. Kraft P, Hunter DJ. 2009. Genetic risk prediction: Are we there yet? N. Engl. J. Med. 360:1701-3
100. Kringlen E, Cramer G. 1989. Offspring of monozygotic twins discordant for schizophrenia. Arch. Gen. Psychiatry 46:873-77 (Pubitemid 19259532)
101. KumarRA, KaraMohamed S, Sudi J, Conrad DF, Brune C, et al. 2008. Recurrent 16p11.2microdeletions in autism. Hum. Mol. Genet. 17:628-38
102. Lambert JC, Mann D, Richard F, Tian J, Shi J, et al. 2005. Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease? J. Neurol. Neurosurg. Psychiatry 76:928-33 (Pubitemid 40916207)
103. Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, et al. 2005. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am. J. Epidemiol. 161:916-28
104. Lencz T, Morgan TV, Athanasiou M, Dain B, Reed CR, et al. 2007. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol. Psychiatry 12:572-80 (Pubitemid 46816774)
105. Levinson DF, Duan J, Oh S,Wang K, Sanders AR, et al. 2011. Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. Am. J. Psychiatry 168:302-16
106. Levy SF, SiegalML. 2008. Network hubs buffer environmental variation in Saccharomyces cerevisiae. PLoS Biol. 6:e264
107. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, et al. 2009. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373:234-39
108. Mackay TF. 2009. The genetic architecture of complex behaviors: lessons from Drosophila. Genetica 136:295-302
109. Mackay TF, Anholt RR. 2006. Of flies and man: Drosophila as a model for human complex traits. Annu. Rev. Genomics Hum. Genet. 7:339-67 (Pubitemid 44627934)
110. Magri C, Sacchetti E, Traversa M, Valsecchi P, Gardella R, et al. 2010. New copy number variations in schizophrenia. PLoS One 5:e13422
111. MaierW,LichtermannD, Franke P,HeunR, Falkai P, RietschelM. 2002. The dichotomy of schizophrenia and affective disorders in extended pedigrees. Schizophr. Res. 57:259-66 (Pubitemid 35240028)
112. MaierW, Lichtermann D, Minges J, Hallmayer J, Heun R, et al. 1993. Continuity and discontinuity of affective disorders and schizophrenia: results of a controlled family study. Arch. Gen. Psychiatry 50:871-83 (Pubitemid 23330979)
113. Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, et al. 2001. Advancing paternal age and the risk of schizophrenia. Arch. Gen. Psychiatry 58:361-67 (Pubitemid 32299532)
114. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. 2009. Finding the missing heritability of complex diseases. Nature 461:747-53
115. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, et al. 2008. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82:477-88
116. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, et al. 2008. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat. Rev. Genet. 9:356-69 (Pubitemid 351556063)
117. McCarthy SE, Makarov V, Kirov G, Addington AM, McClellan J, et al. 2009. Microduplications of 16p11.2 are associated with schizophrenia. Nat. Genet. 41:1223-27
118. McGrath J, Saha S, Chant D, Welham J. 2008. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol. Rev. 30:67-76
119. MeffordHC, Sharp AJ, Baker C, Itsara A, Jiang Z, et al. 2008. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl. J. Med. 359:1685-99
120. Merikangas AK,Corvin AP, GallagherL. 2009. Copy-number variants in neurodevelopmental disorders: promises and challenges. Trends Genet. 25:536-44
121. Merlo CA, BoyleMP. 2003. Modifier genes in cystic fibrosis lung disease. J. Lab. Clin.Med. 141:237-41 (Pubitemid 36432923)
122. Messias EL, Chen CY, Eaton WW. 2007. Epidemiology of schizophrenia: review of findings and myths. Psychiatr. Clin. North Am. 30:323-38 (Pubitemid 47299146)
123. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, et al. 2010. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet. 86:749-64
124. Miller DT, Shen Y,Weiss LA, Korn J, Anselm I, et al. 2009. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J. Med. Genet. 46:242-48
125. Mitchell KJ. 2011. The genetics of neurodevelopmental disease. Curr. Opin. Neurobiol. 21:192-203
126. Mittal VA, Ellman LM, Cannon TD. 2008. Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications. Schizophr. Bull. 34:1083-94
127. Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM, et al. 2010. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am. J. Hum. Genet. 87:618-30
128. Moskvina V, CraddockN,Holmans P, Nikolov I, Pahwa JS, et al. 2009. Gene-wide analyses of genomewide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol. Psychiatry 14:252-60
129. Mouridsen SE, Rich B, Isager T, Nedergaard NJ. 2008. Psychiatric disorders in individuals diagnosed with infantile autism as children: a case control study. J. Psychiatr. Pract. 14:5-12 (Pubitemid 351158843)
130. Mulle JG, Dodd AF,McGrath JA, Wolyniec PS,Mitchell AA, et al. 2010. Microdeletions of 3q29 confer high risk for schizophrenia. Am. J. Hum. Genet. 87:229-36
131. Murphy KC, Jones LA, Owen MJ. 1999. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch. Gen. Psychiatry 56:940-45 (Pubitemid 29480131)
132. Need AC, Ge D, Weale ME, Maia J, Feng S, et al. 2009. A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet. 5:e1000373
133. Neill J. 1990. Whatever became of the schizophrenogenic mother? Am. J. Psychother. 44:499-505
134. Nestler EJ, Hyman SE. 2010. Animal models of neuropsychiatric disorders. Nat. Neurosci. 13:1161-69
135. Ng MY, Levinson DF, Faraone SV, Suarez BK, DeLisi LE, et al. 2009. Meta-analysis of 32 genome-wide linkage studies of schizophrenia. Mol. Psychiatry 14:774-85
136. O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, et al. 2008. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat. Genet. 40:1053-55
137. Owen MJ, Craddock N, O'Donovan MC. 2010. Suggestion of roles for both common and rare risk variants in genome-wide studies of schizophrenia. Arch. Gen. Psychiatry 67:667-73
138. Pagnamenta AT, Wing K, Sadighi Akha E, Knight SJ, Bolte S, et al. 2009. A 15q13.3 microdeletion segregating with autism. Eur. J. Hum. Genet. 17:687-92
139. Pe'er I, Yelensky R, Altshuler D, Daly MJ. 2008. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol. 32:381-85 (Pubitemid 351656309)
140. Pritchard JK. 2001. Are rare variants responsible for susceptibility to complex diseases? Am. J. Hum. Genet. 69:124-37 (Pubitemid 32614025)
141. Pulver AE, Karayiorgou M, Wolyniec PS, Lasseter VK, Kasch L, et al. 1994. Sequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12-q13.1: Part 1. Am. J. Med. Genet. 54:36-43 (Pubitemid 24066659)
142. Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, et al. 1994. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J. Nerv. Ment. Dis. 182:476-78 (Pubitemid 24263483)
143. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, et al. 2009. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748-52
144. Rapoport J, Chavez A, Greenstein D, Addington A, Gogtay N. 2009. Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. J. Am. Acad. Child Adolesc. Psychiatry 48:10-18
145. RavindranMS, Patel ZM, Adhia RA, D'Souza AK, Babu S. 2005. Validity of analysis of FMRPexpression in blood smears as a screening test for fragile X syndrome in the Indian population. J. Clin. Lab. Anal. 19:120-23 (Pubitemid 40746137)
146. Rees J. 2002. Complex disease and the new clinical sciences. Science 296:698-700
147. Reich DE, Lander ES. 2001. On the allelic spectrum of human disease. Trends Genet. 17:502-10 (Pubitemid 32763048)
148. Remschmidt H, Theisen FM. 2005. Schizophrenia and related disorders in children and adolescents. J. Neural Transm. 112 (Suppl. 69):121-41 (Pubitemid 43066718)
149. Risch N. 1990. Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet. Epidemiol. 7:3-16 (Pubitemid 20162221)
150. RischN. 1990. Linkage strategies for genetically complex traits: I: multilocusmodels.Am. J. Hum. Genet. 46:222-28
151. Rosenthal D, Wender PH, Kety SS, Schulsinger F, Welner J, Ostergaard L. 1968. Schizophrenics' offspring raised in adoptive homes. J. Psychiatr. Res. 6:377-91
152. Roth TL, Lubin FD, Sodhi M, Kleinman JE. 2009. Epigenetic mechanisms in schizophrenia. Biochim. Biophys. Acta 1790:869-77
153. R̈ udin E. 1916. Zur Vererbung und Neuenstehung der Dementia Praecox. Berlin: Springer
154. Rujescu D, Ingason A, Cichon S, Pietilainen OP, Barnes MR, et al. 2009. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum. Mol. Genet. 18:988-96
155. Rutherford SL. 2000. From genotype to phenotype: buffering mechanisms and the storage of genetic information. Bioessays 22:1095-105 (Pubitemid 32010519)
156. Sanders AR, Duan J, Levinson DF, Shi J, He D, et al. 2008. No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Am. J. Psychiatry 165:497-506 (Pubitemid 351694293)
157. Schadt EE. 2009. Molecular networks as sensors and drivers of common human diseases. Nature 461:218-23
158. 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 63:1368-76 (Pubitemid 44878520)
159. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, et al. 2007. Strong association of de novo copy number mutations with autism. Science 316:445-49 (Pubitemid 46651493)
160. Sebat J, Levy DL,McCarthy SE. 2009. Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders. Trends Genet. 25:528-35
161. Sharp AJ, Mefford HC, Li K, Baker C, Skinner C, et al. 2008. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat. Genet. 40:322-28 (Pubitemid 351311774)
162. Shi J, Levinson DF,Duan J, Sanders AR, Zheng Y, et al. 2009. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460:753-57
163. Shi YY, He G, ZhangZ,TangW,Zhang J Jr., et al. 2008. A study of rare structural variants in schizophrenia patients and normal controls from Chinese Han population. Mol. Psychiatry 13:911-13
164. Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, et al. 2010. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J. Med. Genet. 47:332-41
165. Shprintzen RJ, Goldberg R, Golding-Kushner KJ, Marion RW. 1992. Late-onset psychosis in the velocardio-facial syndrome. Am. J. Med. Genet. 42:141-42
166. Sklar P, Smoller JW, Fan J, Ferreira MA, Perlis RH, et al. 2008. Whole-genome association study of bipolar disorder. Mol. Psychiatry 13:558-69 (Pubitemid 351704939)
167. Smalley SL. 1997. Genetic influences in childhood-onset psychiatric disorders: autism and attentiondeficit/hyperactivity disorder. Am. J. Hum. Genet. 60:1276-82 (Pubitemid 27258057)
168. Sporns O, Tononi G, Kotter R. 2005. The human connectome: a structural description of the human brain. PLoS Comput. Biol. 1:e42
169. Stahlberg O, Soderstrom H, Rastam M, Gillberg C. 2004. Bipolar disorder, schizophrenia, and other psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum disorders. J. Neural. Transm. 111:891-902 (Pubitemid 38916282)
170. St. Clair D, Xu M, Wang P, Yu Y, Fang Y, et al. 2005. Rates of adult
171. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, et al. 2009. Common variants conferring risk of schizophrenia. Nature 460:744-47
172. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, et al. 2008. Large recurrent microdeletions associated with schizophrenia. Nature 455:232-36
173. Sullivan PF, Kendler KS, Neale MC. 2003. Schizophrenia as a complex trait: evidence from a metaanalysis of twin studies. Arch. Gen. Psychiatry 60:1187-92 (Pubitemid 37494071)
174. Sullivan PF, Lin D, Tzeng JY, van den Oord E, Perkins D, et al. 2008. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol. Psychiatry 13:570-84 (Pubitemid 351704941)
175. Sun J, Jia P, Fanous AH, Webb BT, van den Oord EJ, et al. 2009. A multi-dimensional evidencebased candidate gene prioritization approach for complex diseases: schizophrenia as a case. Bioinformatics 25:2595-6602
176. Susser ES, Lin SP. 1992. Schizophrenia after prenatal exposure to the Dutch HungerWinter of 1944-1945. Arch. Gen. Psychiatry 49:983-88
177. Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, et al. 2007. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39:319-28 (Pubitemid 46328498)
178. Tam GW, van de Lagemaat LN, Redon R, Strathdee KE, Croning MD, et al. 2010. Confirmed rare copy number variants implicate novel genes in schizophrenia. Biochem. Soc. Trans. 38:445-51
179. Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, et al. 2008. Multiple loci identified in a genome-wide association study of prostate cancer. Nat. Genet. 40:310-15 (Pubitemid 351311773)
180. Thornhill R, Moller AP. 1997. Developmental stability, disease and medicine. Biol. Rev. Camb. Philos. Soc. 72:497-548 (Pubitemid 27490280)
181. Tienari P. 1991. Interaction between genetic vulnerability and family environment: the Finnish adoptive family study of schizophrenia. Acta Psychiatr. Scand. 84:460-65
182. Tienari P, Sorri A, Lahti I, Naarala M, Wahlberg KE, et al. 1985. The Finnish adoptive family study of schizophrenia. Yale J. Biol. Med. 58:227-37 (Pubitemid 15019378)
183. Tienari P, Wynne LC, Moring J, Lahti I, Naarala M, et al. 1994. The Finnish adoptive family study of schizophrenia: implications for family research. Br. J. Psychiatry 164 (Suppl. 23):20-26 (Pubitemid 24141699)
184. Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, et al. 2009. Paternal age as a risk factor for schizophrenia: How important is it? Schizophr. Res. 114:1-5
185. Traherne JA. 2008. HumanMHCarchitecture and evolution: implications for disease association studies. Int. J. Immunogenet. 35:179-92 (Pubitemid 351678693)
186. Ullmann R, Turner G, Kirchhoff M, Chen W, Tonge B, et al. 2007. Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation. Hum. Mutat. 28:674-82 (Pubitemid 47047294)
187. Valles V, Van Os J, Guillamat R, Gutierrez B, Campillo M, et al. 2000. Increased morbid risk for schizophrenia in families of in-patients with bipolar illness. Schizophr. Res. 42:83-90 (Pubitemid 30163074)
188. Van Es MA, van den Berg LH. 2009. Alzheimer's disease beyond APOE. Nat. Genet. 41:1047-48
189. Van Os J, Kapur S. 2009. Schizophrenia. Lancet 374:635-45
190. Van Snellenberg JX, de Candia T. 2009. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch. Gen. Psychiatry 66:748-55
191. Verheij C, Bakker CE, de Graaff E, Keulemans J, Willemsen R, et al. 1993. Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. Nature 363:722-24 (Pubitemid 23227649)
192. Vrijenhoek T, Buizer-Voskamp JE, van der Stelt I, Strengman E, Sabatti C, et al. 2008. Recurrent CNVs disrupt three candidate genes in schizophrenia patients. Am. J. Hum. Genet. 83:504-10
193. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, et al. 2008. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539-43 (Pubitemid 351590668)
194. Wang H, Feng R, Phillip Wang L, Li F, Cao X, Tsien JZ. 2008. CaMKII activation state underlies synaptic labile phase of LTP and short-term memory formation. Curr. Biol. 18:1546-54
195. Wassink TH, Piven J, Vieland VJ, Jenkins L, Frantz R, et al. 2005. Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene. Am. J.Med. Genet. B Neuropsychiatr. Genet. 136B:36-44 (Pubitemid 40917526)
196. Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, et al. 2008. Genome-wide association analysis identifies 20 loci that influence adult height. Nat. Genet. 40:575-83 (Pubitemid 351601210)
197. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, et al. 2008. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358:667-75 (Pubitemid 351240746)
198. Wellcome Trust Case Control Consort. 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661-78
199. Welsh MJ. 2010. Targeting the basic defect in cystic fibrosis. N. Engl. J. Med. 363:2056-57
200. Wender PH, Rosenthal D, Kety SS, Schulsinger F,Welner J. 1974. Crossfostering: a research strategy for clarifying the role of genetic and experiential factors in the etiology of schizophrenia. Arch. Gen. Psychiatry 30:121-28
201. Willatt L, Cox J, Barber J, Cabanas ED, Collins A, et al. 2005. 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am. J. Hum. Genet. 77:154-60 (Pubitemid 40848047)
202. Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, et al. 2011. Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum. Mol. Genet. 20:387-91
203. Worden FG, Childs B, Matthysse S, Gershon ES. 1976. Frontiers of psychiatric genetics. Neurosci. Res. Program Bull. 14:8-86
204. Wray NR, Goddard ME, Visscher PM. 2007. Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res. 17:1520-28 (Pubitemid 47529436)
205. Wray NR, Visscher PM. 2010. Narrowing the boundaries of the genetic architecture of schizophrenia. Schizophr. Bull. 36:14-23
206. Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. 2008. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat. Genet. 40:880-85 (Pubitemid 351913650)
207. Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, et al. 2010. Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 42:565-69
208. Yang J, Visscher PM, Wray NR. 2010. Sporadic cases are the norm for complex disease. Eur. J. Hum. Genet. 18:1039-43
209. Zahir FR, Baross A, Delaney AD, Eydoux P, FernandesND, et al. 2008.Apatient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha. J. Med. Genet. 45:239-43 (Pubitemid 351518730)
210. Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, et al. 2008. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40:638-45 (Pubitemid 351601209)
211. Zweier C, de Jong EK, ZweierM, Orrico A, Ousager LB, et al. 2009. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am. J. Hum. Genet. 85:655-66