CLINICAL HANDBOOK OF SCHIZOPHRENIA

6. Genetics 57Question 2: What Are the Relative Contributions of Genesand Environment?Once a disorder has been established as familial, it becomes necessary to determinewhether that pattern is attributable to the inheritance of genes or to shared familial andother environmental factors. It is also important to quantify the contribution that genesmake relative to that made by environmental factors, because this may not only encourageor discourage future molecular genetic studies but also influence the decisions madeby individuals seeking genetic counseling. These questions can be answered by both twinand adoption studies.Twin StudiesIn twin study designs, identical (monozygotic [MZ]) and fraternal (dizygotic [DZ]) twinpairs are included if at least one pair member is affected with schizophrenia. Twin pairsare deemed “concordant” if both members of the pair have schizophrenia, and discordantif only one member of the pair is affected. The ratio of concordant:discordant MZtwin pairs is then compared to the ratio of concordant:discordant DZ twin pairs.MZ twins are derived from the same zygote and share 100% of their genetic material.In contrast, DZ twins result from separate fertilizations and share, on average, 50%of their genes—no more or less than any other pair of siblings. Thus, a typical MZ twinpair will have 50% more genes in common than a typical DZ twin pair. The degree ofsimilarity in environmental exposures between members of an MZ twin pair should beno different than that between members of a DZ twin pair, however. Thus, any differencein concordance for schizophrenia between the two types of twin pairs can be attributed tothe effects of the additional gene sharing in the MZ twins. In other words, sharing 50%more genes in common can be attributed as the sole factor responsible for any increasedphenotypic similarity among MZ twin pairs relative to DZ twin pairs.Concordance for schizophrenia that is higher for MZ twin pairs than for DZ twinpairs is a good indication that there is a genetic contribution to the disorder; if MZ andDZ twin pairs have approximately equal concordance rates, environmental factors aremore strongly implicated. Frequently, concordance rates in twin pairs are used to estimatethe heritability of a disorder, which is the degree to which genetic factors influencevariability in the manifestation of the phenotype. Heritability in the broad sense is the ratioof genetic to phenotypic variances, or the proportion of variance in schizophrenia riskthat is accounted for by variability in genetic factors. A heritability of 1.0 indicates thatall variability in the phenotype is due to genetic factors alone. In contrast, a heritability ofzero attributes all phenotypic variation to environmental factors.Adoption StudiesAn alternative to the twin method for parsing the genetic and environmental contributionsto schizophrenia is the adoption study, in which ascertainment targets individualswith schizophrenia who were involved in an adoption, either as an adoptee or as anadoptive or biological parent of an adoptee. Next, the biological and adoptive relatives ofthese probands are ascertained and evaluated for the presence of the disorder. The rate ofschizophrenia among the biological relatives of probands is then compared to the rate ofthe disorder among adoptive relatives of the probands.Children adopted at an early age have a genetic relationship to their biological parentsand an environmental relationship to their adopted parents. Thus, adoption studiescan determine whether biological or adoptive (environmental) relationships account for