Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-29T21:26:48.277Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetics of Schizophrenia: Current Findings and Issues

Published online by Cambridge University Press:  07 November 2014

James L. Kennedy ,
Michele T. Pato ,
Amy Bauer ,
Celia Carvalho  and
Carlos N. Pato
Get access Rights & Permissions [Opens in a new window]

Abstract

The genetics of schizophrenia are characterized by a set of complex questions, with few answers forthcoming. However, molecular genetic approaches remain the most promising avenue to the understanding of etiologic mechanisms. Powerful discoveries may arise in the near future from candidate gene studies that are benefiting from the extensive neurobiology research in schizophrenia over the past decades. Furthermore, there are promising new divisions of the phenotype into more manageable subtypes that may make both candidate gene and genome scan studies more revealing. The following review discusses selected highlights of the epidemiology, molecular genetic strategies, candidate genes, and genome scan investigations in schizophrenia.

Type
Feature Articles
Information
CNS Spectrums , Volume 4 , Issue 5: Molecular Genetics: Part One , May 1999 , pp. 17 - 21
Copyright
Copyright © Cambridge University Press 1999

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Gottesman, II, Shields, J. Schizophrenia: The Epigenetic Puzzle. Cambridge, UK: Cambridge University Press; 1982.Google Scholar
2.Pato, CN, Lander, ES, Schultz, SC. Prospects for the genetic analysis of schizophrenia. Schizophr Bull. 1989;15:365–372.CrossRefGoogle ScholarPubMed
3.Pato, CN, Azevedo, MH, Pato, MT, et al.Selection of homogeneous populations for genetic study: The Portuguese Genetics of Psychosis Project. Am J Med Genet. 1997;74:286–288.3.0.CO;2-O>CrossRefGoogle Scholar
4.Tsuang, MT, Faraone, SV. The Genetics of Mood Disorders. Baltimore, Md: Johns Hopkins; 1990.Google Scholar
5.Faraone, SV, Kremen, WS, Tsuang, MT. Genetic transmission of major affective disorders: quantitative models and linkage analyses. Psychol Bull. 1990;108:109–127.CrossRefGoogle ScholarPubMed
6.Greenberg, DA. There is more than one way to collect data for linkage analysis: what a study of epilepsy can tell us about linkage strategy for psychiatric disease. Arch Gen Psychiatry. 1992;49:745–750.CrossRefGoogle ScholarPubMed
7.Goldin, LR. The increase in type 1 error rates in linkage studies when multiple analyses are carried out on the same data: a simulation study [abstract]. Am J Hum Genet. 1990;47:A180.Google Scholar
8.Goldin, LR, Weeks, DE. Two-locus models of disease: comparison of likelihood and nonparametric methods [abstract]. Am J Hum Genet. 1993;53(suppl):1006.Google Scholar
9.Weeks, DE, Lehner, T, Squires-Wheeler, E, Kaufmann, C, Ott, J. Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis. Genet Epidemiol. 1990;7:237–243.CrossRefGoogle ScholarPubMed
10.Risch, N. Linkage strategies for genetically complex traits: II. The power of affected relative pairs. Am J Hum Genet. 1990;46:229–241.Google ScholarPubMed
11.Falk, CT, Rubenstein, P. Haplotype relative risk: an easy reliable way to construct a proper control sample for risk calculations. Ann Hum Genet. 1987;51:227–233.CrossRefGoogle ScholarPubMed
12.Terwilliger, JD, Ott, J. A haplotype-based “haplotype relative risk” approach to detecting allele associations. Hum Hered. 1992;42:337–346.CrossRefGoogle Scholar
13.Kruglyak, L, Daly, M, Daly, MPR, Lander, E. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996;58:1347–1363.Google ScholarPubMed
14.Straub, RE, MacLean, CJ, O'Neill, FA, et al.A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nat Genet. 1995;11:287–293.CrossRefGoogle ScholarPubMed
15.Lander, E, Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995;11:241–247.CrossRefGoogle ScholarPubMed
16.Kennedy, JL. Molecular genetics of the dopamine receptor genes and schizophrenia. In: Niznik, HB, ed. Dopamine Receptors and Transporters. New York, NY: Marcel Dekker; 1993:581–593.Google Scholar
17.Kennedy, JL, Billett, EA, Macciardi, FM, et al.Association study of dopamine D3 receptor gene and schizophrenia. Am J Med Genet. 1995;60:558–562.CrossRefGoogle ScholarPubMed
18.Dourado, A, Coelho, I, Macedo, A, et al.Association study of DRD3 and schizophrenia in Portuguese patients: effect of population stratification. Psiquiatria Clinica. 1997;18:49–53.Google Scholar
19.Williams, J, Spurlock, G, Holmans, P, et al.A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia. Mol Psychiatry. 1998;3:141–149.CrossRefGoogle ScholarPubMed
20.Coelho, I, Macedo, A, Valente, J. Association study of serotonin receptors and schizophrenia in a Portuguese population. Psiquiatria Clinica. 1997;18:41–47.Google Scholar
21.Williams, J, McGuffin, P, Nothen, M, Owen, MJ. Metaanalysis of association between the 5-HT2A receptor T102C polymorphism and schizophrenia. EMASS Collaborative Group. European Multicentre Association Study of Schizophrenia. Lancet. 1997;26:122.Google Scholar
22.Vicente, AM, Kennedy, JL. The genetics of neurodevelopment and schizophrenia. In: Keshavan, M, Murray, RM, eds. Neurodevelopment and Adult Psychopathology. Cambridge, UK: Cambridge University Press; 1997:3156.Google Scholar
23.Freedman, R, Coon, H, Myles-Worsley, M, et al.Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA. 1997;94:587–592.CrossRefGoogle ScholarPubMed
24.Chandy, KG, Fantino, E, Wittekindt, O, et al.Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder? Mol Psychiatry. 1998;3:32–37.CrossRefGoogle ScholarPubMed
25.Kendler, KS, Diehl, SR. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull. 1993;19:261–285.CrossRefGoogle ScholarPubMed
26.Karayiorgou, M, Gogos, JA. Dissecting the genetic complexity of schizophrenia. Mol Psychiatry. 1997;2:211–223.CrossRefGoogle ScholarPubMed
27.Levinson, DF, Mahtani, MM, Nancarrow, DJ, et al.Genome scan of schizophrenia. Am J Psychiatry. 1998;155:741–750.Google ScholarPubMed
28.Straub, RE, MacLean, CJ, O'Neill, FA, Walsh, D, Kendler, KS. Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families. Mol Psychiatry. 1997;2:148–155.CrossRefGoogle ScholarPubMed
29.Schwab, SG, Eckstein, GN, Hallmayer, J, et al.Evidence suggestive of a locus on chromosome 5q31 contributing to susceptibility for schizophrenia in German and Israeli families by multipoint affected sib-pair linkage analysis. Mol Psychiatry. 1997;2:156–160.CrossRefGoogle ScholarPubMed
30.Cao, Q, Martinez, M, Zhang, J, et al.Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics. 1997;43:1–8.CrossRefGoogle Scholar
31.Diehl, SR, Wang, S, Detera-Wadleigh, S, et al.Evidence suggesting possible SCA1 gene involvement in schizophrenia. Am J Hum Genet. 1994;55S:867.Google Scholar
32.Moises, HW, Yang, L, Kristbjarnarson, H, et al.An international two-stage genome-wide search for schizophrenia susceptibility genes. Nat Genet. 1995;11:321–324.CrossRefGoogle ScholarPubMed
33.Schizophrenia Linkage Collaborative Group for Chromosomes 3, 6, and 8. Additional support for schizophrenia linkage on chromosomes 6 and 8: a multicenter study. Am J Med Genet. 1996;67:580–594.3.0.CO;2-P>CrossRefGoogle Scholar
34.Pulver, AE, Lasseter, VK, Kasch, L, et al.Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes. Am J Med Genet. 1995;60:252–260.CrossRefGoogle ScholarPubMed
35.Kendler, KS, MacLean, CJ, O'Neill, FA, et al.Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families. Am J Psychiatry. 1996;153:1534–1540.Google ScholarPubMed
36.Faraone, SV, Matise, T, Svrakic, DM, et al.Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium. Am J Med Genet. 1998;81:290–295.3.0.CO;2-Y>CrossRefGoogle ScholarPubMed
37.Straub, RE, MacLean, CJ, Martin, RB, et al.A schizophrenia locus may be located in region 10p15-11. Am J Med Genet. 1998;81:296–301.3.0.CO;2-S>CrossRefGoogle Scholar
38.Maziade, M, Raymond, V, Cliche, D, et al.Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia. Am J Med Genet. 1995;60:522–528.CrossRefGoogle ScholarPubMed
39.Lin, MW, Sham, P, Hwu, HG, Collier, D, Murray, R, Powell, JF. Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations. Hum Genet. 1997;99:417–420.CrossRefGoogle Scholar
40.Wildenauer, DB, Schwab, SG, Hallmayer, J, et al.Genome scan for autosomal genes confering risk to schizophrenia in a German/Israeli sample [abstract]. Am J Med Genet. 1998;81:454.Google Scholar
41.Gill, M, Vallada, H, Collier, D, et al.A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22). Am J Med Genet. 1996;67:40–45.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
42.Dann, J, DeLisi, LE, Devoto, M, et al.A linkage study of schizophrenia to markers within Xp11 near the MAOB gene. Psychiatry Res. 1997;70:131–143.CrossRefGoogle ScholarPubMed
43.Moldin, SO. The maddening hunt for madness genes. Nat Genet. 1997;17:127–129.CrossRefGoogle ScholarPubMed
44.Delepine, M, Pociot, F, Habita, C, et al.Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6. Am J Hum Genet. 1998;60:174–187.Google Scholar
45.Cloninger, CR, Kauffman, CA, Faraone, SV, et al.Genome-wide search for schizophrenia susceptibility loci: The NIMH Genetics Initiative and Millennium Consortium. Am J Med Genet. 1998;81:275–281.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
46.Kauffman, CA, Suarez, B, Malaspina, D, et al.NIMH Genetics Initiative Millennium Consortium: linkage analysis of African-American pedigrees. Am J Med Genet. 1998;81:282–289.3.0.CO;2-W>CrossRefGoogle Scholar