New findings from genetic association studies of schizophrenia

Journal of Human Genetics

Volumn 54, Issue 1, 2009, Pages 9-14

  Williams, Hywel J ^a   Owen, Michael J ^a   O'Donovan, Michael C ^a,b  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b Wales Heart Research Institute   (United Kingdom)

Author keywords

Association study; Candidate gene; Copy number variant; Genome wide association study; Schizophrenia

Indexed keywords

GENE; GENE NUMBER; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC IDENTIFICATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; PATHOPHYSIOLOGY; REVIEW; SCHIZOPHRENIA; COPY NUMBER VARIATION; GENETIC PREDISPOSITION; GENETICS;

DNA COPY NUMBER VARIATIONS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; SCHIZOPHRENIA;

EID: 58849166224     PISSN: 14345161     EISSN: None     Source Type: Journal    
DOI: 10.1038/jhg.2008.7     Document Type: Review

References (58)

1. Cardno, A. G. & Gottesman, I. I. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am. J. Med. Genet. 97, 12-17 (2000).
2. Gottesman, I. I. Schizophrenia Genesis: The Origins of Madness, Henry Holt & Company Inc.: New York, NY, USA, 296pp (1991).
3. McGue, M. & Gottesman, I. I. A single dominant gene still cannot account for the transmission of schizophrenia. Arch. Gen. Psychiatry 46, 478-480 (1990).
4. Risch, N. Linkage strategies for genetically complex traits. I. Multilocus models. Am. J. Hum. Genet. 46, 222-228 (1990).
5. Wellcome Trust Case Control Consortium. Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controls. Nature 447, 661-678 (2007).
6. Gottesman, I. I. & Shields, J. A polygenic theory of schizophrenia. Proc. Natl Acad. Sci. USA 58, 199-205 (1967).
7. Lewis, C. M., Levinson, D. F., Wise, L. H., DeLisi, L. E., Straub, R. E., Hovatta, I. et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am. J. Hum. Genet. 73, 34-48 (2003).
8. St Clair, D., Blackwood, D., Muir, W., Carothers, A., Walker, M., Spowart, G. et al. Association within a family of a balanced autosomal translocation with major mental illness. Lancet 336, 13-16 (1990).
9. Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516-1517 (1996).
10. Straub, R. E., Jiang, Y., MacLean, C. J., Ma, Y., Webb, B. T., Myakishev, M. V. 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. 71, 337-348 (2002).
11. Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S. et al. Neuregulin 1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892 (2002).
12. Chumakov, I., Blumenfeld, M., Guerassimenko, O., Cavarec, L., Palicio, M., Abderrahim, H. et al. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc. Natl Acad. Sci. USA 99, 13675-13680 (2002).
13. Owen, M. J., Craddock, N. & O'Donovan, M. C. Schizophrenia: genes at last? Trends Genet. 21, 518-525 (2005).
14. Owen, M. J., O'Donovan, M. C. & Harrison, P. J. Schizophrenia: a genetic disorder of the synapse? BMJ 330, 158-159 (2005).
15. Millar, J. K., Wilson-Annan, J. C., Anderson, S., Christie, S., Taylor, M. S., Semple, C. A. et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum. Mol. Genet. 9, 1415-1423 (2000).
16. Harrison, P. J. & Weinberger, D. R. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry 10, 40-68 (2005); image 5.
17. Ross, C. A., Margolis, R. L., Reading, S. A., Pletnikov, M. & Coyle, J. T. Neurobiology of schizophrenia. Neuron 52, 139-153 (2006).
18. Zeggini, E., Scott, L. J., Saxena, R., Voight, B. F., Marchini, J. L., Hu, T. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638-645 (2008).
19. Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J. Y., Sackler, R. S., Haynes, C. et al. Complement factor H polymorphism in age-related macular degeneration. Science 308, 385-389 (2005).
20. Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S. et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl Acad. Sci. USA 90, 1977-1981 (1993).
21. Todd, J. A., Bell, J. I. & McDevitt, H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329, 599-604 (1987).
22. Allen, N. C., Bagade, S., McQueen, M. B., Ioannidis, J. P., Kavvoura, F. K., Khoury, M. J. et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat. Genet. 40, 827-834 (2008).
23. Duan, J., Wainwright, M. S., Comeron, J. M., Saitou, N., Sanders, A. R., Gelernter, J. et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum. Mol. Genet. 12, 205-216 (2003).
24. Seeman, P. & Lee, T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217-1219 (1975).
25. Watanabe, Y., Nunokawa, A., Kaneko, N. & Someya, T. The tryptophan hydroxylase 1 (TPH1) gene and risk of schizophrenia: a moderate-scale case-control study and meta-analysis. Neurosci. Res. 59, 322-326 (2007).
26. Ioannidis, J. P., Boffetta, P., Little, J., O'Brien, T. R., Uitterlinden, A. G., Vineis, P. et al. Assessment of cumulative evidence on genetic associations: interim guidelines. Int. J. Epidemiol. 37, 120-132 (2008).
27. Jonsson, E. G., Larsson, K., Vares, M., Hansen, T., Wang, A. G., Djurovic, S. et al. Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 147B, 976-982 (2008).
28. Ma, G., He, Z., Fang, W., Tang, W., Huang, K., Li, Z. et al. The Ser9Gly polymorphism of the dopamine D3 receptor gene and risk of schizophrenia: an association study and a large meta-analysis. Schizophr. Res. 101, 26-35 (2008).
29. Talbot, K., Eidem, W. L., Tinsley, C. L., Benson, M. A., Thompson, E. W., Smith, R. J. et al. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J. Clin. Invest. 113, 1353-1363 (2004).
30. Williams, N. M., O'Donovan, M. C. & Owen, M. J. Is the dysbindin gene (DTNBP1) a susceptibility gene for schizophrenia? Schizophr. Bull. 31, 800-805 (2005).
31. Bray, N. J., Preece, A., Williams, N. M., Moskvina, V., Buckland, P. R., Owen, M. J. et al. Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Hum. Mol. Genet. 14, 1947-1954 (2005).
32. Weickert, C. S., Straub, R. E., McClintock, B. W., Matsumoto, M., Hashimoto, R., Hyde, T. M. et al. Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Arch. Gen. Psychiatry 61, 544-655 (2004).
33. Kumamoto, N., Matsuzaki, S., Inoue, K., Hattori, T., Shimizu, S., Hashimoto, R. et al. Hyperactivation of midbrain dopaminergic system in schizophrenia could be attributed to the down-regulation of dysbindin. Biochem. Biophys. Res. Commun. 345, 904-909 (2006).
34. Numakawa, T., Yagasaki, Y., Ishimoto, T., Okada, T., Suzuki, T., Iwata, N. et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum. Mol. Genet. 13, 2699-2708 (2004).
35. Lizuka, Y., Sei, Y., Weinberger, D. R. & Straub, R. E. Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization. J. Neurosci. 27, 12390-12395 (2007).
36. Bertram, L. Genetic research in schizophrenia: new tools and future perspectives. Schizophr. Bull. 34, 806-812 (2008).
37. Manolio, T. A., Brooks, L. D. & Collins, F. S. A HapMap harvest of insights into the genetics of common disease. J. Clin. Invest. 118, 1590-1605 (2008).
38. Mah, S., Nelson, M. R., Delisi, L. E., Reneland, R. H., Markward, N., James, M. R. et al. Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Mol. Psychiatry 11, 471-478 (2006).
39. Sullivan, P. F., Lin, D., Tzeng, J. Y., van den Oord, E., Perkins, D., Stroup, T. S. et al. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol. Psychiatry 13, 570-584 (2008).
40. Dudbridge, F. & Gusnanto, A. Estimation of significance thresholds for genomewide association scans. Genet. Epidemiol. 32, 227-234 (2008).
41. O'Donovan, M. C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V. et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat. Genet. 40, 1053-1055 (2008).
42. Craddock, N., O'Donovan, M. C. & Owen, M. J. Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophr. Bull. 32, 9-16 (2006).
43. Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M. et al. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum. Mol. Genet. 17, 458-465 (2008).
44. Kirov, G., Zaharieva, I., Georgieva, L., Moskvina, V., Nikolov, I., Cichon, S. et al. A genome-wide association study in 574 schizophrenia trios using DNA pooling. Mol. Psychiatry (2008); e-pub ahead of print 11 March 2008.
45. Shifman, S., Johannesson, M., Bronstein, M., Chen, S. X., Collier, D. A., Craddock, N. J. et al. Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genet. 4, e28 (2008).
46. Hong, S. E., Shugart, Y. Y., Huang, D. T., Shahwan, S. A., Grant, P. E., Hourihane, J. O. et al. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat. Genet. 26, 93-96 (2000).
47. Craddock, N., O'Donovan, M. C. & Owen, M. J. Genome-wide association studies in psychiatry: lessons from early studies of non-psychiatric and psychiatric phenotypes. Mol. Psychiatry 13, 649-653 (2008).
48. McCarroll, S. A., Kuruvilla, F. G., Korn, J. M., Cawley, S., Nemesh, J., Wysoker, A. et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet. 40, 1166-1174 (2008).
49. Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T. et al. Strong association of de novo copy number mutations with autism. Science 316, 445-449 (2007).
50. Autism Genome Project Consortium. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39, 319-328 (2007).
51. Lindsay, E. A., Greenberg, F., Shaffer, L. G., Shapira, S. K., Scambler, P. J. & Baldini, A. Submicroscopic deletions at 22q11.2: variability of the clinical picture and delineation of a commonly deleted region. Am. J. Med. Genet. 56, 191-197 (1995).
52. Murphy, K. C., Jones, L. A. & Owen, M. J. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch. Gen. Psychiatry 56, 940-945 (1999).
53. Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M. et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539-543 (2008).
54. Rujescu, D., Ingason, A., Cichon, S., Pietilainen, O. P., Barnes, M. R., Toulopoulou, T. et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum. Mol. Genet. (2008); e-pub ahead of print 22 October 2008.
55. Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A. & Karayiorgou, M. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat. Genet. 40, 880-885 (2008).
56. International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237-241 (2008).
57. Stefansson, H., Rujescu, D., Cichon, S., Pietilainen, O. P., Ingason, A., Steinberg, S. et al. Large recurrent microdeletions associated with schizophrenia. Nature 455, 232-236 (2008).
58. Mefford, H. C., Sharp, A. J., Baker, C., Itsara, A., Jiang, Z., Buysse, K. et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl. J. Med. 359, 1685-1699 (2008).