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Various environmental variables are hypothesized to operate differentially within identical and fraternal twin pairs. To the extent that these factors are correlated with behavioral outcomes, such as alcohol or drug abuse, traditional twin studies of concordance may be biased. Self-ratings of within-pair emotional closeness, assessed in 169 same-sex twin pairs ascertained through alcohol and drug treatment centers, were used to determine the impact of the twin relationship on concordance for alcohol dependence (N = 130 twin pairs) and other drug abuse and/or dependence (N = 85 twin pairs). In general, identical twin pairs reported significantly closer relationships than fraternal twin pairs, and female twin pairs reported significantly closer relationships than male twin pairs. The data did not indicate an overall effect of closeness on co-twin risk for alcohol dependence. In contrast, closeness was significantly related to co-twin risk for other drug abuse and/or dependence. However, the MZ/DZ concordance difference for other drug abuse and/or dependence remained significant when the effects of within-pair closeness were controlled. Thus, the initial zygosity and sex differences in concordance for substance use disorders cannot be explained solely by differences in twin relationship due to closeness as assessed in this study.

Comorbid drug and mental disorders were assessed in 63 monozygotic (MZ) and 67 dizygotic (DZ) twin pairs. DSM-III alcohol dependence was heritable in males when probands had a comorbid DSM-III drug or mental disorder but not when probands had only alcohol dependence. For males, significantly higher cross-MZ than cross-DZ correlations were found between alcohol dependence in probands and certain mental and drug disorders in cotwins. In contrast, females showed higher within-twin than cross-MZ correlations and similar cross-MZ and cross-DZ correlations between alcohol dependence and all mental and drug disorders. These results suggest comorbidity between alcohol and certain drug and mental disorders in males in epidemiological surveys may be due in part to genetic influences.

The multiple regression analysis of twin data in which a cotwin's score is predicted from that of a proband (the member of a twin pair selected because of a deviant score) and the coefficient of relationship provides a powerful test of genetic etiology (DeFries and Fulker: Behav Genet 15:467-473, 1985). Moreover, when an augmented model containing an interaction term is fitted to the same data set, direct estimates of heritability (h2) and the proportion of variance owing to shared environmental influences (c2) are also obtained. In the present paper, the expected partial regression coefficients estimated from these models are derived, and the flexibility of the general approach is illustrated. An extended model is formulated for the analysis of data from combined samples of affected and control twin pairs that yields tests for differential h2 and c2 in the two groups as well as pooled estimates of these parameters. The application of these models is illustrated by an analysis of data from reading-disabled and control twin pairs. Because of the ease, flexibility, and utility of the multiple regression analysis of twin data, it is an appealing alternative to more traditional model-fitting approaches.