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Letters to the Editor |

Gene–Brain Structure Relationships: Arbitrary Assumptions of Heterogeneity Generate Unfalsifiable Claims—Reply

Hugh M. D. Gurling, MD, MPhil, FRCPsych; Hugo Critchley, MB, ChB, DPhil, MRCPsych; Susmita R. Datta, BSc; Andrew McQuillin, PhD; Ekaterina Blaveri, PhD; Srinivasa Thirumalai, MD, MRCPsych; Jonathan Pimm, MPhil, MBBS, MRCPsych; Robert Krasucki, BSc, MBBS, MRCPsych; Gursharan Kalsi, PhD; Digby Quested, MD, MRCPsych; Jacob Lawrence, MBBS, BSc, MRCPsych; Nicholas Bass, MB, ChB, BSc, MRCPsych; Khalid Choudhury, BSc; Vinay Puri, BSc; Owen O’Daly, BSc; David Curtis, MBBS, MD, PhD, MRCPsych; Douglas Blackwood, PhD, MRCPsych; Walter Muir, PhD, MRCPsych; Anil K. Malhotra, MD; Robert W. Buchanan, MD; Catriona D. Good, MB, ChB, FFRad, FRCR; Richard S. J. Frackowiak, MD, DSc, FRCP, FMedSci; Raymond J. Dolan, MD, FRCPsych, FMedSci
Arch Gen Psychiatry. 2007;64(9):1098-1099. doi:10.1001/archpsyc.64.9.1098.
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In reply

We do not agree with the criticisms that Crow and DeLisi make of our research. The claim that we have been arbitrarily assuming locus heterogeneity in schizophrenia on a post hoc basis is at odds with what has already been published in numerous cytogenetic, linkage, and allelic association studies. Crow and DeLisi remain isolated in their views about the genetics of schizophrenia, and they cling to the belief that schizophrenia is linked only to a single locus on the X chromosome. The widely accepted view is that there is heterogeneity of linkage or locus heterogeneity in schizophrenia. For example, chromosome 22 deletions are associated with velo-cardio-facial syndrome and schizophrenia.1 Other cytogenetic abnormalities associated with schizophrenia are on chromosomes 1, 2, and 11.2,3 Furthermore, linkage and association studies of schizophrenia have now produced statistically significant and replicable results that can only be explained by the existence of locus heterogeneity, with different loci increasing susceptibility to schizophrenia in subgroups of families.4 Furthermore, the presence of replicated positive linkages to schizophrenia on specific chromosomal regions has successfully predicted where the genes associated with schizophrenia have later been fine-mapped using familial and case-control allelic association studies.


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