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Confirming Unexpressed Genotypes for Schizophrenia:  Risks in the Offspring of Fischer's Danish Identical and Fraternal Discordant Twins

Irving I. Gottesman, PhD, FRCPsych(Hon); Aksel Bertelsen, MD
Arch Gen Psychiatry. 1989;46(10):867-872. doi:10.1001/archpsyc.1989.01810100009002.
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• Margit Fischer reported in 1971 that the risk of schizophrenia in the offspring of her Danish schizophrenic monozygotic twins and their normal cotwins was equal and not different from the risks in the children of schizophrenics in the literature. All of her identical and fraternal twins who had children and all of their offspring have been followed up through the Danish National Psychiatric Register as of 1985, some 18 years after study by Fischer. The morbid risk (age-corrected) for schizophrenia and schizophrenia-related disorders in the offspring of schizophrenic identical twins is 16.8%; it is 17.4% in their normal cotwins' offspring. The risks in the offspring of schizophrenic fraternal twins and their normal cotwins are 17.4% and 2.1%, respectively. The results suggest that discordance in identical twins may primarily be explained by the capacity of a schizophrenic genotype or diathesis to be unexpressed unless it is released by some kinds of environmental, including nonfamilial, stressors. Sporadic cases and phenocopies caused by cerebral abnormalities, diseases, or viruses would thus be deemphasized as necessary or sufficient explanatory causes for schizophrenia in our study but could account for some of the remaining discordance. Infrequent phenocopies should encourage linkage researchers, but unexpression of genotypes will frustrate them.

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