Strategies In Humans The Twin Method

The twin method is one of the most powerful and frequently used tools to determine genetic and environmental influences on variation in traits. It compares the resemblance between genetically identical, mono-zygotic (MZ) twins to the resemblance between fraternal or dizygotic (DZ) twins. MZ twins have the same allelic combinations at all their genes, whereas DZ twins share, on average, 50% of allele combinations (counting only those genes for which their parents had different genotypes). The shared environment for both is very comparable. Hence, the demonstration that MZ twins are more similar than DZ twins for a certain trait points to a genetic contribution to the variation in this trait. Efficient use of the information available in the variances and covariances of geneti cally related subjects (e.g., twins) can be done with a statistical technique called structural equation modeling. Basically, the total variance in a trait is decomposed into several contributing factors: (i) additive genetic variance, which results from the additive effects of the two alleles of all contributing genes; (ii) dominance genetic variance, which results from the nonadditive effects of the two alleles for all genes showing a dominance effect; (iii) shared environmental variance, which results from environmental events shared by both members of the twin pair (e.g., school and diet); and (iv) unique environmental variance, which results from nonshared environmental effects and also includes measurement error. The influence of confounding variables such as age or socioeconomic status can be incorporated in the model. In addition, a further refinement from univariate to multivariate models allows exploration of the question of whether any covariance between different variables is genetically and/or environmentally determined.

There are some pitfalls in the twin method that need to be avoided. First, there is the matter of zygosity. An underestimation of the number of MZs will lower estimates of genetic effects because they will raise the fraternal twin correlation and lower the correlation of identical twins. Conversely, underestimation of DZs will raise estimates of genetic influences. Correct zygosity has become even more important with the increasing use of DZ twins for the location of quantitative trait loci (QTL). An accurate zygosity diagnosis is now easier than ever. Usually, six to eight highly polymorphic DNA markers are adequate to discriminate between MZ and DZ twins. The second pitfall is the so-called equal environments assumption, which holds that the degree of environmental similarity is comparable in MZ and DZ twins. At first, this assumption seems quite justified. Both types of twins share the same womb and are reared in the same family, all at the same time. However, the two types of twins may be treated differentially. For instance, MZ twins may be treated more similarly than fraternal twins. If this is true and MZ twins would experience more similar environmental influences than DZ twins, the genetic contribution to the variation of the trait under investigation would be overestimated. Although there is evidence that the equal environment assumption is violated, studies on a range of traits suggest that the violations do not seriously compromise the validity of the twin method. Finally, like any other study, twin studies make sense only when statistical power is adequate. In earlier studies samples were often too small because experimenters thought they could use the same sample size required to compare means. Power studies have demonstrated that large samples are necessary for an accurate estimate of the presence and size of genetic influences, especially if heritability is low.

The use of the twin method in the genetic analysis of human aggression has been demonstrated in a recent study. Using three types of questionnaires, nine different aspects of aggression were measured: physical assault, indirect hostility, irritability, negativism, resentment, suspicion and verbal hostility, trait anger, and type A behavior. All these aspects showed moderate to fair heritabilities, varying from 23% for indirect hostility to 53% for resentment and suspicion. A multivariate analysis revealed two common additive genetic and two common environmental factors. Hence, two sets of genes and two sets of unique environmental factors give an adequate description of the pattern of associations between the nine measured aspects of human aggression. Of course, the nine measures are also individually influenced by specific additive and/or environmental factors. This replicates an extensive literature on twins and aggression or related concepts such as antisocial behavior and hostility (thoroughly reviewed elsewhere). The correlation between MZs is not perfect, showing that unique environmental factors play a role in these types of aggression. In all studies, however, MZs are more similar than DZs, indicating a genetic contribution to the variation in aggressive behavior. Finally, results from a related design, the adoption method, further corroborate the existence of a significant genetic contribution to aggression.

The obvious question remains, which genes are responsible for the variation in aggression? Also, where are they located on the chromosomes? What proteins do they encode? Where are they expressed in the brain? Are they always expressed or only during a certain time period? Actually, there is a gene that is specifically associated with a behavioral phenotype that includes disturbed regulation ofimpulsive aggression. However, before we discuss this gene, we review the techniques to find "behavioral" genes.

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