Have schizophrenia genes been found?

Current Opinion in Psychiatry

Volumn 17, Issue 2, 2004, Pages 107-113

  Elkin, Amanda ^a   Kalidindi, Sridevi ^a   McGuffin, Peter ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Genetics; Schizophrenia

Indexed keywords

AMINO ACID OXIDASE; CATECHOL METHYLTRANSFERASE; DOPAMINE 3 RECEPTOR; DYSBINDIN; NEU DIFFERENTIATION FACTOR; PROLINE DEHYDROGENASE; PROTEIN; PROTEIN G72; RGS PROTEIN; SEROTONIN 2A RECEPTOR; UNCLASSIFIED DRUG;

BIPOLAR DISORDER; CHROMOSOME 22Q; CHROMOSOME DELETION; GENE; GENE DELETION; GENE FUNCTION; GENETIC SUSCEPTIBILITY; HAPLOTYPE; HUMAN; MOLECULAR GENETICS; PROTEIN FUNCTION; REVIEW; SCHIZOPHRENIA; VELOCARDIOFACIAL SYNDROME;

EID: 1542299053     PISSN: 09517367     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001504-200403000-00007     Document Type: Review

References (55)

1. Riley BP, McGuffin P. Linkage and associated studies of schizophrenia. Am J Med Genet 2000; 97:23-44.
2. Owen M, O'Donovan M, Gottesman I. Schizophrenia. In: P McGuffin, MJ Owen, II Gottesman, editors. Psychiatric genetics and genomics. Oxford: Oxford University Press; 2002.
3. Thomson G. Significance levels in genome scans. Adv Genet 2001; 42:475-486.
4. Badner J, Gershon E. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002; 7:405-411. The first attempt to put together all of the published genome scans and perform a combined analysis.
5. Levinson DF, Levinson MD, Segurdo R, Lewis CM. Genome scan meta-analysis of schizophrenia and bipolar disorder. Part 1: Methods and power analysis. Am J Hum Genet 2003; 73:17-33. An important methods paper introducing a new approach to metaanalysis of linkage data.
6. Lewis CM, Levinson DF, Wise LH, et al. Genome scan meta-analysis of schizophrenia and bipolar disorder. Part II: Schizophrenia. Am J Hum Genet 2003; 73:34-48. A comprehensive metaanalysis that helpfully clarifies a hitherto complicated and at times confusing picture.
7. Sham P, McGuffin P. Linkage and association. In: P McGuffin, MJ Owen, II Gottesman, editors. Psychiatric genetics and genomics. Oxford: Oxford University Press; 2002.
8. Stefansson H, Sigurdsson E, Steinthorsdottir V. Neuregulin1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71:877-892. The first report on the role of neuregulin.
9. Stefansson H, Sarginson J, Kong A, et al. Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. Am J Hum Genet 2003; 72:83-87. Convincing support for Ref. [8••].
10. Williams N, Preece A, Spurlock G. Support for the genetic variation in neuregulin-1 and susceptibility to schizophrenia. Mol Psychiatry 2003; 8:485-487. Convincing support for Ref. [8••].
11. Yang J, Ruan Y. Association study of neuregulin 1 gene with schizophrenia. Mol Psychiatry 2003; 8:706-709. Convincing support for Ref. [8••].
12. Davis K, Stewart D, Friedman J. White matter changes in schizophrenia. Arch Gen Psychiatry 2003; 60:443-456.
13. Hakak Y, Walker J, Li C. Genome-wide expression analysis reveals dysregulation of myelantion-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A 2001; 98:4746-4751.
14. Law A. Neuregulin-1 in the human brain. Am J Psychiatry 2003; 160:1392.
15. Straub RE, Jiang Y, MacLean CJ, et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 2002; 71:337-348. The first report on the role of dysbindin.
16. Benson M, Newey S, Martin-Rebdon E, et al. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. J Biol Chem 2001; 276:24232-24241.
17. Schwab SG, Knapp M, Mondadon S, et al. Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad pairs. Am J Hum Genet 2003; 72:185-190. Convincing support for Ref. [15••].
18. Morris DW, McGhee KA, Schwaiger S, et al. No evidence for the association of the dysbindin gene [DTNBP1] with schizophrenia in an Irish population-based study. Schizophr Res 2004, 60:167-172.
19. Williams NM, Preece A, Morris DW, et al. Identification in two independent samples of a novel schizophrenia risk haplotype of the dystobrevin binding protein gene (DTNBP1). Arch Gen Psychiatry 2004; (in press).
20. Chumankov I, Blumenfield M, Guerassimenko O, et al. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. PNAS 2002; 99:13675-13680. Report of an association between schizophrenia and a novel primate specific gene, G72, that interacts with DAAO, a gene at a separate locus, to confer susceptibilty.
21. Hattori E, Liu C, Badner JA, et al. Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series. Am J Hum Genet 2003; 72:1131-1140. Evidence that the genes implicated in Ref. [20••] also play a role in bipolar disorder.
22. Liu H, Heat SC, Sobin C, et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. PNAS 2002; 99:3717-3722.
23. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardio facial syndrome. Arch Gen Psychiatry 1999; 56:940-945.
24. Murphy KC. Schizophrenia and velo-cardio-facial syndrome. Lancet 2002; 359:426-430. An authoritative review of the evidence regarding chromosome 22q interstitial deletions and schizophrenia.
25. Jacquet H, Raux G, Thibaut F, et al. PRODH mutations and hyperprolinaemia in a subset of schizophrenia patients. Hum Mol Genet 2002; 11:2243-2249.
26. Gogos JA, Santha M, Takaacs Z. The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat Genet 1999; 21:434-439.
27. Williams HJ, Williams N, Spurlock G, et al. Association between PRODH and schizophrenia is not confirmed. Mol Psychiatry 2003; 8:644-645.
28. Chen E, Lam L, Chen R. Neuropsychological correlates of sustained attention in schizophrenia. Schizophr Res 1997; 24:299-310.
29. Daniels J, Williams N, Williams J. No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol-O-methyltransferase activity. Am J Psychiatry 1996; 153:268-270.
30. de Chaldee M, Corbex M, Campion D. No evidence for linkage between COMT and schizophrenia in a French population. Psychiatr Res 2001; 102:87-90.
31. Egan MF, Goldberg TE, Kolachana BS. Effects of COMT Val 108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 2001; 98:6917-6922.
32. Herken H, Erdal M. Catechol-O-methytransferase gene polymorphism in schizophrenia: evidence for association between symptomatology and schizophrenia. Psychiatr Genet 2001; 11:105-109.
33. Kunugi H, Vallada HP, Sham PC. Catechol-O-methytransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families. Psychiatr Genet 1997; 7:97-101.
34. Li T, Sham PC, Vallada H, Xie T. Preferential transmission of the high activity allele of COMT in schizophrenia. Psychiatr Genet 1996; 6:131-133.
35. Liou Y, Tsai S, Hong C. Association analysis of functional catechol-O-methyltransferase gene polymorphism in schizophrenic patients in Taiwan. Neuropsychobiology 2001; 43:11-14.
36. Norton N, Kirov G, Zammit S. Schizophrenia and functional polymorphisms in the MAOA and COMT genes: no evidence for association of epistasis. Am J Hum Genet 2002; 114:491-496.
37. Ohmori O, Shinkai T, Kojima H. Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics. Neurosci Lett 1998; 243:109-112.
38. Semwal P, Prasad S, Bhatia T. Family based association studies of monaminergic gene polymorphisms among North Indians with schizophrenia. Mol Psychiatry 2001; 6:220-224.
39. Strous R, Bark N, Woerner M, Lachman HM. Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia. Biol Psychiatry 1997; 41:493-495.
40. Weinberger DR, Egan MF, Bertolino A. Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry 2001; 50:825-844.
41. Shifman S, Bronstein M, Sternfield M, et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 2002; 71:1296-1302. A study suggesting with a high degree of probability that COMT is involved in the etiology of schizophrenia but implicating a different set of variants to that in Ref. [31] and other previous studies.
42. Bray NJ, Buckland PR, Williams NM, et al. A haplotype implicated in schizophrenia susceptibilty is associated with reduced COMT expression in human brain. Am J Hum Genet 2003; 73:152-161. An investigation of the functional significance of COMT polymorphisms associated with schizophrenia in Ref. [41••].
43. Wondoni I, Stine CO, Mitchell BD, et al. Association between Val108/158 Met polymorphism of the COMT gene and schizophrenia. Am J Med Genet Part B 2003; 120B:47-50.
44. Matsumoto M, Weickert CS, Beltaifa S, et al. Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia. Neuropsychopharmacology 2003; 28:1521-1530.
45. Mirnics K, Middleton F, Marquez A. Molecular characterisation of schizophrenia viewed by microarray analysis of gene expression in the prefrontal cortex. Neuron 2000; 28:53-67.
46. Brzustowicz L, Hodgkinson K, Chow E. Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science 2000; 288:678-682.
47. Chowdari K, Mimics K, Semwal P. Association and linkage analysis of RGS4 polymorphisms in schizophrenia. Mol Genet 2002; 11:1373-1380.
48. O'Donovan MC, Williams NM, Owen MJ. Recent advances in the genetics of schizophrenia. Hum Mol Genet 2003; 12:R125-R133.
49. Polesskaya O, Sakalov B. Differential expression of the 'C' and 'T' alleles of the 5HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J Neurosci Res 2002; 67:812-822.
50. Williams J, McGuffin P, Nothen M. Meta-analysis of the association between the 5-HT2a receptor T102C polymorphism and schizophrenia. The Lancet 1997; 348:1221.
51. Lohmueller K, Pearce C, Pike M. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003; 33:177-182. An important metaanalysis that supports the involvement of DRD3 and 5HT2A polymorphisms in schizophrenia and a reminder that many of the problems in the molecular genetics of schizophrenia are held in common with other complex diseases.
52. Harrison P, Owen M. Genes for schizophrenia? Recent findings and their pathophysiological implications. The Lancet 2003; 361:417-419. A thoughtful essay that attempts to integrate the likely roles of the 'new' schizophrenia genes and their products in glutamatergic neurotransmission.
53. Manji HK, Gottesman II, Gould TD. Signal transduction and genes-to-behaviors pathways in psychiatric diseases. Science STKE 2003; 207:49. Another and even more ambitious attempt at integration and explanation, proposing that calcineurin plays a pivotal role in modulating abnormalities of neurotransmission and brain development in schizophrenia.
54. Gerber DJ, Hall D, Miyakawa T, et al. Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit. Proc Natl Acad Sci U S A 2003; 100:8933-8938. The first report of association with a variant in a gene encoding a calcineurin sub unit.
55. Cardno AG, Rijsdijk FV, Sham PC, et al. A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry 2002; 159:539-545. A statistical analysis of a large twin series putting forward the hitherto heretical view that some genes may predispose to both schizophrenia and bipolar disorder. This is now beginning to be borne out by linkage and association studies.