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.
