Hostname: page-component-7c8c6479df-94d59 Total loading time: 0 Render date: 2024-03-28T22:14:16.327Z Has data issue: false hasContentIssue false

The emperors of the schizophrenia polygene have no clothes

Published online by Cambridge University Press:  21 April 2008

T. J. Crow*
Affiliation:
SANE POWIC, University Department of Psychiatry, Warneford Hospital, Oxford, UK
*
*Address for correspondence: Professor T. J. Crow, SANE POWIC, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK. (Email: tim.crow@psych.ox.ac.uk)

Abstract

A substantial body of research literature, identified by nine out of ten papers on genetics in the recent ISI research front on schizophrenia, claims to have established associations between aspects of the disease and sequence variation in specific candidate genes. These candidatures have proven unreplicated in large sibling pair linkage surveys and a targeted association study. Even if the case for an association be regarded as a lucky guess (assuming one gene in 30 000 was guessed right) the large linkage and association studies provide no evidence of sequence variation relating to psychosis at any of these gene loci. Thus this body of work must be regarded as an indicator of the extent to which the ‘eye of faith’ is able to discern meaning in complex data when none is present.

Type
Editorial Review
Copyright
Copyright © 2008 Cambridge University Press

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

Book, JA (1953). Schizophrenia as a gene mutation. Acta Genetica et Statistica Medica 4, 133139.Google Scholar
Callicott, JH, Straub, RE, Pezawas, L, Egan, MF, Mattay, VS, Hariri, AR, Verchinski, BA, Meyer-Lindenberg, A, Balkissoon, R, Kolachana, B, Goldberg, TE, Weinberger, DR (2005). Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proceedings of the National Academy of Sciences USA 102, 86278632.Google Scholar
Cannon, TD, Hennah, W, van Erp, TGM, Thompson, PM, Lonnqvist, J, Huttunen, M, Gasperoni, T, Tuulio-Henriksson, A, Pirkola, T, Toga, AW, Kaprio, J, Mazziotta, J, Peltonen, L (2005). Association of DISC1/TRAX haploytpes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of General Psychiatry 62, 12051213.Google Scholar
Cloninger, CR (2002). The discovery of susceptibility genes for mental disorders. Proceedings of the National Academy of Sciences USA 99, 1336513367.Google Scholar
Craddock, N, O'Donovan, MC, Owen, MJ (2005). The genetics of schizophrenia and bipolar disorder: dissecting psychosis. Journal of Medical Genetics 42, 193204.Google Scholar
Crow, TJ (1993). Sexual selection, Machiavellian intelligence and the origins of psychosis. Lancet 342, 594598.Google Scholar
Crow, TJ (2002). The Speciation of Modern Homo sapiens. Oxford University Press: Oxford.Google Scholar
Crow, TJ (2007). How and why genetic linkage has not solved the problem of psychosis: review and hypothesis. American Journal of Psychiatry 164, 1321.Google Scholar
Fan, JB, Zhang, CS, Gu, NF, Li, XW, Sun, WW, Wang, HY, Feng, GY, Clair, DS, He, L (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biological Psychiatry 57, 139144.Google Scholar
Green, EK, Raybould, R, McGregor, S, Gordon-Smith, K, Heron, J, Hyde, S, Grozeva, D, Hamshere, M, Williams, N, Owen, MJ, O'Donovan, MC, Jones, L, Jones, I, Kirov, G, Craddock, N (2005). Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder. Archives of General Psychiatry 62, 642648.Google Scholar
Harrison, PJ, Owen, MJ (2003). Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet 361, 417419.Google Scholar
Harrison, PJ, Weinberger, DR (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry 10, 4068.Google Scholar
Hashimoto, T, Bergen, SE, Nguyen, QL, Xu, BJ, Monteggia, LM, Pierri, JN, Sun, ZX, Sampson, AR, Lewis, DA (2005). Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. Journal of Neuroscience 25, 372383.Google Scholar
Iwamoto, K, Bundo, M, Kato, T (2005). Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Human Molecular Genetics 14, 241253.Google Scholar
Jablensky, A, Sartorius, N, Ernberg, G, Anker, M, Korten, A, Cooper, JE, Day, R, Bertelsen, A (1992). Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization Ten Country Study. Psychological Medicine (Suppl.) 20, 197.Google Scholar
Millar, JK, Pickard, BS, Mackie, S, James, R, Christie, S, Buchanan, SR, Malloy, MP, Chubb, JE, Huston, E, Baillie, GS, Thomson, PA, Hill, EV, Brandon, NJ, Rain, JC, Camargo, LM, Whiting, PJ, Houslay, MD, Blackwood, DHR, Muir, WJ, Porteous, DJ (2005). DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 310, 11871191.Google Scholar
Neves-Pereira, M, Cheung, J, Pasdar, A, Zhang, F, Breen, G, Yates, P, Sinclair, M, Crombie, C, Walker, N, St Clair, DM (2005). BDNF gene is a risk factor for schizophrenia in a Scottish population. Molecular Psychiatry 10, 208212.Google Scholar
Owen, MJ, Craddock, N, Jablensky, A (2007). The genetic deconstruction of psychosis. Schizophrenia Bulletin 33, 905911.Google Scholar
Owen, MJ, Craddock, N, O'Donovan, MC (2005). Schizophrenia: genes at last? Trends in Genetics 21, 518525.Google Scholar
Owen, MJ, Williams, NM, O'Donovan, MC (2004). The molecular genetics of schizophrenia: new findings promise new insights. Molecular Psychiatry 9, 1427.Google Scholar
Petryshen, TL, Middleton, FA, Kirby, A, Aldinger, KA, Purcell, S, Tahl, AR, Morley, CP, McGann, CP, Gentile, KL, Rockwell, GN, Medeiros, HM, Carvalho, C, Macedo, A, Dourado, A, Valente, J, Ferreira, CP, Patterson, NJ, Azevedo, MH, Daly, MJ, Pato, CN, Pato, MT, Sklar, P (2005). Support for involvement of neuregulin 1 in schizophrenia pathophysiology. Molecular Psychiatry 10, 366374.Google Scholar
Sanders, AR, Duan, J, Levinson, DF, Shi, J, He, D, Hou, C, Burrell, GJ, Rice, JP, Nertney, DA, Olincy, A, Rozic, P, Vinogradov, S, Buccola, NG, Mowry, BJ, Freedman, R, Amin, F, Black, DW, Silverman, JM, Bylerley, WF, Crowe, RR, Cloninger, CR, Martinez, M, Gejman, PV (2008). No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. American Journal of Psychiatry 165, 497506.Google Scholar
Straub, RE, Weinberger, DR (2006). Schizophrenia genes – famine to feast. Biological Psychiatry 60, 8183.Google Scholar
Turner, JMA (2007). Meiotic sex chromosome inactivation. Development 134, 18231831.Google Scholar