General Method. Twin studies often examine the relative importance of genetic and environmental influences for behavioral characteristics and diseases. The use of twin studies in research is attractive because it uses the natural biological phenomenon of twinning in order to differentiate
environmental and genetic factors in disease etiology. Using principles of biology and genetics, the twin phenomenon implies that monozygotic (MZ) twins are, for most purposes, genetically identical, whereas dizygotic (DZ)
twins share the same amount of genes as would two normal siblings. That is dizygotic twins share on average half of their genes, identical by descent, and monozygotic twins share all their genes, thus being genetically identical. To use this phenomenon of twinning in research, one compares the similarity of monozygotic twin pairs for a trait or a disorder with the similarity of dizygotic twin pairs, and thereby can detect environmental and genetic effects, and most importantly, has the ability to quantify the magnitude of these effects (85-87). This is especially attractive when examining co-occurring disorders because twin studies control, to a substantial extent, genetic and
environmental factors, thus helping to elucidate the complex interactions of biological, psychological, and environmental factors involved in co-morbid conditions (54, 87).
Classic twin modeling partitions the variation in liability to a disorder by means of decomposition of variance (88). This is done using structured equation modeling (SEM), as performed by various software programs such as Mx (89). This analysis uses path diagrams and matrix algebra to
determine the decomposition of variances and covariances, and in doing so is able to determine what percent of the demonstrated association is due to additive genetic effects (a2) (also known as heritability), common
environmental effects (c2), and unique environmental effects (e2) (87, 88), which also encapsulates measurement error. This analysis is heavily
dependent on knowing the pairwise zygosity of the twins as well as their affection status.
Results of Twin Studies in IBS. Four twin studies examining the genetic liability to IBS are described in Table 1.6. All three twin studies were population-based samples of twin pairs. Methodologically all but the third study employed classic twin methods, examining monozygotic (MZ) and dizygotic (DZ) concordance rates, whereas the third study employed a co-twin control design. A drawback of these studies is the lack of use of a consensus definition of IBS, either Manning, Rome I, or Rome II. The Svedberg et al. (90) study employed a diagnostic algorithm to define IBS that is similar to the Rome criteria, however use of a consensus definition would help
comparability and consistency of IBS definition across different studies.
The study by Morris-Yates et al. demonstrated a higher concordance of IBS in MZ twins than in DZ twins (33.3% versus 13.3%, respectively) (91). Similar results were reported in the twin study by Levy et al., where the MZ twin concordance was 17.2% and DZ twin concordance was 8.4% for IBS (61). While the concordances are considerably higher in identical (MZ) twins, there is not a perfect concordance of 100%, suggesting moderate to high environmental influences (86). Morris-Yates et al. alluded to this in their analysis where 58% of the difference in liability to functional bowel disorders (FBD) was attributed to genetic control (91), and not 100% as perfect MZ
concordance would demonstrate. One problem with this study is that the assessed phenotype of FBD includes a mix of individuals with IBS, functional abdominal bloating, functional constipation, functional diarrhea, and functional abdominal pain. Thus the results may not be true of the individual disorders that fall under the realm of FBD. Together, these results are suggestive of both genetic and environmental contributions to the etiology of IBS.
In contrast, the classic twin study by Mohammed et al. (92)
demonstrated similar IBS concordance rates between MZ and DZ twin pairs (28% and 27%, respectively). Additionally, the best-fitting classic twin model did not contain a variable for heritability, but only variables for common and unique environmental influences. Thus this study demonstrated that genetic factors have little or no influence over IBS. The main difference between this twin study and the previous studies was the use of the most recent, more restrictive Rome II IBS criteria.
The third twin study by Svedberg et al. performed a case-control and co-twin analysis. The case-control analysis demonstrated associations between IBS and eating disorders (OR 2.4; 95% CI 1.1-5.1), urological problems (OR 3.3; 95% CI 1.3-8.2), poor self-rated health (OR 1.8; 95% CI 1.0-3.2), eating allergies (OR 9.0; 95% CI 1.4-60.1), and rheumatoid arthritis (OR 3.2; 95% CI 1.1-9.4) (90). The co-twin analysis examined 58 disease discordant MZ twin pairs and only the association between urologic problems
and IBS remained (OR 4.0; 95% CI 1.0-16.8), suggesting a common etiology not attributable to genetic effects (90). The associations between IBS and eating disorders, eating allergies, and rheumatoid arthritis decreased in the co-twin analysis, suggesting genetic as well as family environmental effects on these associations (90).
In summary, three of these twin studies are supportive of both genetic and environmental components to IBS; however several problems were noted. First, a consensus definition of IBS was not employed, and one study used the broader term of functional bowel disorders and applied the results to IBS. Thus a better defined phenotype may add to this existing knowledge. Another criticism of twin studies is the inability to separate similarity due to common environment (from conception onward) from similarity due to genetic influences (86). Despite these limitations, there were strengths. These studies all used population-based twin registries and twin study
methodologies. Taking the results of twin and family studies together, there is accumulating evidence suggestive of genetic and environmental contributions to IBS.