Informing Prevention and Intervention Policy Using Genetic Studies of Resistance
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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.
KeywordsGenetic resistance Resilience Prevention High-risk design
Compliance with Ethical Standards
This work was supported by the National Institute on Drug Abuse (NIDA) Grants R01DA036525 and R01DA039408 and the National Institute on Alcoholism and Alcohol Abuse Grant K01AA020333.
Conflict of Interest
Drs. Latendresse, Vanyukov, and Maher have no potential conflicts of interest to report.
For this type of study ethical approval is not required.
For this type of study, formal consent is not required.
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