50 whys to look for genes: 29. Mental illness–Interaction of “genetic risk” with many environmental factors for behavioral traits

Kendler and colleagues examine behavioral traits in relation to a wealth of environmental factors over the life course as well as to the relatedness of the individuals (Kendler and Prescott 2006). In Kendler et al. (2002), for example, data on over 1,900 twins are used to fit the incidence of major depression to an additive model that incorporates many environmental factors and a “genetic risk” factor. This last factor is derived from the incidence of major depression in the co-twin and parents, with adjustments made for the degree of relatedness of the twins (monozygotic versus dizygotic). The model accounts for 52% of the variance in the trait and provides a picture of development that is rich and plausible (see figure below).

Complications

As Kendler et al. (2002, 1133) note their “results…should be treated with caution because of problems with causal inference, retrospective recall bias, and the limitations of a purely additive statistical model.”

Another limitation of a purely additive model is that the values of the correlations or path coefficients are dependent on the network of factors chosen by the researchers. For Kendler and colleagues, this dependency might not seem to be a noteworthy limitation, given, as the paper’s title—“towards a comprehensive developmental model”—indicates, a very wide range of factors are taken into account. Moreover, in the initial network every factor is linked to every other factor. The links are then pruned to arrive at a less saturated network, but it is the data analysis that indicates which links in the network have low correlations or path coefficients. Finally, before arriving at the final published network, the researchers examine whether the degree of fit of the model to the data is sensitive to the inclusion or omission of factors.  These virtues notwithstanding, the results remain dependent on the network of factors chosen by the researchers. The research of Kendler et al. does not include factors that correspond to therapeutic interventions or to social changes that have led to the rising incidence of depression. (Kendler [pers. comm.] explains that their research is intended to be basic, not applied, science.

TableI.1

References

Adapted from page 137ff of Taylor, P. J.  (2014) Nature-Nurture? No: Moving the Sciences of Variation and Heredity Beyond the Gaps.

Kendler, K. S., C. O. Gardner, et al. (2002). “Towards a comprehensive developmental model for major depression in women.” American Journal of Psychiatry 159: 1133-1145.

Kendler, K. S. and C. A. Prescott (2006). Genes, Environment, and Psychopathology: Understanding the Causes of Psychiatric and Substance Abuse Disorders. New York: The Guilford Press.

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(Introduction to this series of posts)

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