Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-23T14:02:29.987Z Has data issue: false hasContentIssue false

Letter to the Editor: Strong evidence for multiple psychosis susceptibility genes – a rejoinder to Crow

Published online by Cambridge University Press:  10 October 2008

M. C. O'DONOVAN
Affiliation:
School of Medicine, Cardiff University, Heath Park, Cardiff, UK (Email: [email protected])
N. CRADDOCK
Affiliation:
School of Medicine, Cardiff University, Heath Park, Cardiff, UK (Email: [email protected])
M. J. OWEN
Affiliation:
School of Medicine, Cardiff University, Heath Park, Cardiff, UK (Email: [email protected])
Rights & Permissions [Opens in a new window]

Abstract

Type
Correspondence
Copyright
Copyright © 2008 Cambridge University Press

There are many mis-representations of our position in Dr Crow's response (Crow, Reference Crow2008) to our comment on his paper, but given recent empirical developments in genetic research (Maher et al. Reference Maher, Riley and Kendler2008), there is little need, and even less time, to engage in a protracted debate on whether there is a genetic basis to psychosis. In the last 2 months, a synthesis of genome-wide data and large sample sets has convincingly shown that common genetic variants, each of weak effect, are indeed involved in schizophrenia (O'Donovan et al. Reference O'Donovan, Craddock, Norton, Williams, Peirce, Moskvina, Nikolov, Hamshere, Carroll, Georgieva, Dwyer, Holmans, Marchini, Spencer, Howie, Leung, Hartmann, Möller, Morris, Shi, Feng, Hoffmann, Propping, Vasilescu, Maier, Rietschel, Zammit, Schumacher, Quinn, Schulze, Williams, Giegling, Iwata, Ikeda, Darvasi, Shifman, He, Duan, Sanders, Levinson, Gejman, Cichon, Nöthen, Gill, Corvin, Rujescu, Kirov and Owen2008) and bipolar disorder (Ferreria et al. Reference Ferreira, O'Donovan, Meng, Jones, Ruderfer, Jones, Fan, Kirov, Perlis, Green, Smoller, Grozeva, Stone, Nikolov, Chambert, Hamshere, Nimgaonkar, Moskvina, Thase, Caesar, Sachs, Franklin, Gordon-Smith, Ardlie, Gabriel, Fraser, Blumenstiel, Defelice, Breen, Gill, Morris, Elkin, Muir, McGhee, Williamson, MacIntyre, McLean, St Clair, VanBeck, Pereira, Kandaswamy, McQuillin, Collier, Bass, Young, Lawrence, Ferrier, Anjorin, Farmer, Curtis, Scolnick, McGuffin, Daly, Corvin, Holmans, Blackwood, Gurling, Owen, Purcell, Sklar and Craddock2008). Moreover, in schizophrenia, there is now consistent and compelling evidence (The International Schizophrenia Consortium, Reference Stefansson, Rujescu, Cichon, Pietiläinen, Ingason, Steinberg, Fossdal, Sigurdsson, Sigmundsson, Buizer-Voskamp, Hansen, Jakobsen, Muglia, Francks, Matthews, Gylfason, Halldorsson, Gudbjartsson, Thorgeirsson, Sigurdsson, Jonasdottir, Jonasdottir, Bjornsson, Mattiasdottir, Blondal, Haraldsson, Magnusdottir, Giegling, Möller, Hartmann, Shianna, Ge, Need, Crombie, Fraser, Walker, Lonnqvist, Suvisaari, Tuulio-Henriksson, Paunio, Toulopoulou, Bramon, Di Forti, Murray, Ruggeri, Vassos, Tosato, Walshe, Li, Vasilescu, Mühleisen, Wang, Ullum, Djurovic, Melle, Olesen, Kiemeney, Franke, Kahn, Linszen, van Os, Wiersma, Bruggeman, Cahn, Germeys, de Haan, Krabbendam, Sabatti, Freimer, Gulcher, Thorsteinsdottir, Kong, Andreassen, Ophoff, Georgi, Rietschel, Werge, Petursson, Goldstein, Nöthen, Peltonen, Collier, St Clair and Stefansson2008; Stefansson et al. Reference Stefansson, Rujescu, Cichon, Pietiläinen, Ingason, Steinberg, Fossdal, Sigurdsson, Sigmundsson, Buizer-Voskamp, Hansen, Jakobsen, Muglia, Francks, Matthews, Gylfason, Halldorsson, Gudbjartsson, Thorgeirsson, Sigurdsson, Jonasdottir, Jonasdottir, Bjornsson, Mattiasdottir, Blondal, Haraldsson, Magnusdottir, Giegling, Möller, Hartmann, Shianna, Ge, Need, Crombie, Fraser, Walker, Lonnqvist, Suvisaari, Tuulio-Henriksson, Paunio, Toulopoulou, Bramon, Di Forti, Murray, Ruggeri, Vassos, Tosato, Walshe, Li, Vasilescu, Mühleisen, Wang, Ullum, Djurovic, Melle, Olesen, Kiemeney, Franke, Kahn, Linszen, van Os, Wiersma, Bruggeman, Cahn, Germeys, de Haan, Krabbendam, Sabatti, Freimer, Gulcher, Thorsteinsdottir, Kong, Andreassen, Ophoff, Georgi, Rietschel, Werge, Petursson, Goldstein, Nöthen, Peltonen, Collier, St Clair and Stefansson2008) from molecular genetics for a contribution to risk from copy number variation (CNV), variants that result in the deletion or duplication of 1000 bases or more of DNA sequence. Read with an open mind, these recent papers should change Dr Crow's views.

While we make no argument that epigenetic changes are not involved at all, the molecular data clearly show genetic variation is involved. Moreover, the molecular data clearly point to the involvement in psychosis of multiple regions of the genome, not some single sex-linked part of the genome involved in language and speciation as Dr Crow has long proposed. It must surely now be the time for Dr Crow to reject his own hypothesis of a single cause of psychosis, and to use his well-earned reputation in whatever way he can to enhance the ability of geneticists, and epigeneticists (who are often the same people), to get on with the job of tackling the complexities of psychosis for the benefits of our patients.

Declaration of Interest

None.

References

Crow, TJ (2008). Will whole genome association studies sink psychosis research? A response to Collier, Sullivan and O'Donovan [Letter]. Psychological Medicine. Published online: 12 August 2008. doi/10.1017/S0033291708004030.Google Scholar
Ferreira, MAR, O'Donovan, MC, Meng, YA, Jones, IR, Ruderfer, DM, Jones, L, Fan, J, Kirov, G, Perlis, RH, Green, EK, Smoller, JW, Grozeva, D, Stone, J, Nikolov, I, Chambert, K, Hamshere, ML, Nimgaonkar, V, Moskvina, V, Thase, ME, Caesar, S, Sachs, GS, Franklin, J, Gordon-Smith, K, Ardlie, KG, Gabriel, SB, Fraser, C, Blumenstiel, B, Defelice, M, Breen, G, Gill, M, Morris, DW, Elkin, A, Muir, WJ, McGhee, KA, Williamson, R, MacIntyre, DJ, McLean, A, St Clair, D, VanBeck, M, Pereira, A, Kandaswamy, R, McQuillin, A, Collier, DA, Bass, NJ, Young, AH, Lawrence, J, Ferrier, IN, Anjorin, A, Farmer, A, Curtis, D, Scolnick, EM, McGuffin, P, Daly, MJ, Corvin, AP, Holmans, PA, Blackwood, DH, Wellcome Trust Case Control Consortium (WTCCC), Gurling, HM, Owen, MJ, Purcell, SM, Sklar, P, Craddock, NJ (2008). Collaborative genome-wide association analysis of 10,596 individuals supports a role for Ankyrin-G (ANK3) and the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) in bipolar disorder. Nature Genetics 40, 10561058.CrossRefGoogle Scholar
Maher, BS, Riley, BP, Kendler, KS (2008). Psychiatric genetics gets a boost. Nature Genetics 40, 10421044.CrossRefGoogle ScholarPubMed
O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, Nikolov, I, Hamshere, M, Carroll, L, Georgieva, L, Dwyer, S, Holmans, P, Marchini, JL, Spencer, C, Howie, B, Leung, H-T, Hartmann, AM, Möller, H-J, Morris, DW, Shi, Y, Feng, G, Hoffmann, P, Propping, P, Vasilescu, C, Maier, W, Rietschel, M, Zammit, S, Schumacher, J, Quinn, EM, Schulze, TG, Williams, NM, Giegling, I, Iwata, N, Ikeda, M, Darvasi, A, Shifman, S, He, L, Duan, J, Sanders, AR, Levinson, DF, Gejman, P, Molecular Genetics of Schizophrenia Collaboration, Cichon, S, Nöthen, MM, Gill, M, Corvin, A, Rujescu, D, Kirov, G, Owen, MJ (2008). Identification of novel schizophrenia loci by genome-wide association and follow-up. Nature Genetics 40, 10531055.CrossRefGoogle Scholar
Stefansson, H, Rujescu, D, Cichon, S, Pietiläinen, OP, Ingason, A, Steinberg, S, Fossdal, R, Sigurdsson, E, Sigmundsson, T, Buizer-Voskamp, JE, Hansen, T, Jakobsen, KD, Muglia, P, Francks, C, Matthews, PM, Gylfason, A, Halldorsson, BV, Gudbjartsson, D, Thorgeirsson, TE, Sigurdsson, A, Jonasdottir, A, Jonasdottir, A, Bjornsson, A, Mattiasdottir, S, Blondal, T, Haraldsson, M, Magnusdottir, BB, Giegling, I, Möller, HJ, Hartmann, A, Shianna, KV, Ge, D, Need, AC, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Paunio, T, Toulopoulou, T, Bramon, E, Di Forti, M, Murray, R, Ruggeri, M, Vassos, E, Tosato, S, Walshe, M, Li, T, Vasilescu, C, Mühleisen, TW, Wang, AG, Ullum, H, Djurovic, S, Melle, I, Olesen, J, Kiemeney, LA, Franke, B, Genetic Risk and Outcome in Psychosis (GROUP), Kahn, RS, Linszen, D, van Os, J, Wiersma, D, Bruggeman, R, Cahn, W, Germeys, I, de Haan, L, Krabbendam, L, Sabatti, C, Freimer, NB, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Andreassen, OA, Ophoff, RA, Georgi, A, Rietschel, M, Werge, T, Petursson, H, Goldstein, DB, Nöthen, MM, Peltonen, L, Collier, DA, St Clair, D, Stefansson, K (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232236.CrossRefGoogle ScholarPubMed
The International Schizophrenia Consortium (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237241.CrossRefGoogle Scholar