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17. Exploring the Genetics of Resilience through a Polygenic Lens
Empirical research into psychopathology has a strong foundation of identified general risk factors, such as stressful life events. However, not all people who are exposed to stress respond in the same way. Individual differences in stress resilience reflect dynamic interpersonal as well as intrapersonal factors (Laird, Krause, Funes, & Lavretsky, 2019). Resilience is typically operationalized as an outcome residualized over one or more risk factors; for example, internalizing symptoms (such as depression and anxiety) after accounting for stressful life events. In twin and family models, the heritability of resilience is around 30-50% (Boardman, Blalock, & Button, 2008), and is stable over time (Amstadter, Myers, & Kendler, 2014). Although there has not yet been a genome-wide association study (GWAS) of resilience, existing GWAS of related phenotypes (proxies) may provide a starting point for developing our understanding of the molecular genetic underpinnings of the observed heritability of resilience. In a population sample of older US adults (the Health and Retirement Study, NIA U01AG009740), we examined the extent to which polygenic scores derived from GWAS of depression, neuroticism, PTSD, subjective well-being explained variance in resilience. We then compared the utility of these existing genetic predictors to commonly examined demographic characteristics, such as socioeconomic status and gender. These results will be discussed in the context of how genetic data can inform our understanding of why some individuals are more resilient versus susceptible to the development of psychopathology in response to common stressors.
References Amstadter, A. B., Myers, J. M., & Kendler, K. S. (2014). Psychiatric resilience: longitudinal twin study. Br J Psychiatry, 205(4), 275-280. doi: 10.1192/bjp.bp.113.130906 Boardman, J. D., Blalock, C. L., & Button, T. M. (2008). Sex differences in the heritability of resilience. Twin Res Hum Genet, 11(1), 12-27. doi: 10.1375/twin.11.1.12 Juster, F. T., & Suzman, R. (1995). An overview of the Health and Retirement Study. Journal of Human Resources, S7-S56. Laird, K. T., Krause, B., Funes, C., & Lavretsky, H. (2019). Psychobiological factors of resilience and depression in late life. Translational psychiatry, 9(1), 88. doi: 10.1038/s41398-019-0424-7