Informing Prevention and Intervention Policy Using Genetic Studies of Resistance

Abstract

The common paradigm for conceptualizing the influence of genetic and environmental factors on a particular disease relies on the concept of risk. Consequently, the bulk of etiologic, including genetic, work focuses on "risk" factors. These factors are aggregated at the high end of the distribution of liability to disease, the latent variable underlying the distribution of probability and severity of a disorder. However, liability has a symmetric but distinct aspect to risk, resistance to disorder. Resistance factors, aggregated at the low end of the liability distribution and supporting health and recovery, appear to be more promising for effective prevention and intervention. Herein, we discuss existing work on resistance factors, highlighting those with known genetic influences. We examine the utility of incorporating resistance genetics in prevention and intervention trials and compare the statistical power of a series of ascertainment schemes to develop a general framework for examining resistance outcomes in genetically informative designs. We find that an approach that samples individuals discordant on measured liability, a low-risk design, is the most feasible design and yields power equivalent to or higher than commonly used designs for detecting resistance genetic and environmental effects.

The Implications of Genetics for Prevention and Intervention Programming

“…Maher and colleagues (2017) discuss the benefits of incorporating resistance genetics into prevention and intervention trials. Their results suggest that a modified high risk design may yield the greatest statistical power for detecting significant genetic and environmental effects (Maher, Latendresse, & Vanyukov, 2017).…”

Commentary for Special Issue of Prevention Science “Using Genetics in Prevention: Science Fiction or Science Fact?”

“…Other papers in this issue focus on the need to ensure that the incorporation of genetic information into prevention science represents the state of the science(Latendresse, Musci, & Maher, 2017) and/or novel study designs for understanding genetic and environmental influences on behavioral outcomes(Leve et al, 2017; Maher, Latendresse, & Vanyukov, 2016). Latendresse et al(2017) provide an overview of the history and current methods used in large-scale genetic analyses, with guidelines for how to conduct genetically informative studies.…”

“…Latendresse et al(2017) provide an overview of the history and current methods used in large-scale genetic analyses, with guidelines for how to conduct genetically informative studies. Leve et al(2017) discuss the use of different natural designs to disentangle genetic and environmental influences in order to identify “true” environmental effects, and Maher et al(2016) discuss the novel strategy of focusing on finding genes involved in resistance, rather than risk, and how best to design studies to do this.…”

“…Accordingly, GPS for outcomes such as depression will have to serve as proxies for genetic predispositions to actual constructs of interest, such as emotion regulation (with the assumption that part of the genetic predisposition to depression likely involves mechanisms related to emotion regulation). Maher et al (2016) in this issue make a compelling case for the importance of pursuing genes involved in resistance as a complement to the identification of risk genes. Psychiatric genetics has focused nearly exclusively on finding genes involved in why people develop disorders; studying why some people are particularly likely to remain unaffected would likely be extremely beneficial in helping us understand health-related outcomes as well.…”