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Polygenic liability, stressful life events and risk for secondary-treated depression in early life
A nationwide register-based case-cohort study
Musliner, K. L., Andersen, K. K., Agerbo, E., Albiñana, C., Vilhjalmsson, B. J., Rajagopal, V. M., Bybjerg-grauholm, J., Bækved-hansen, M., Pedersen, C. B., Pedersen, M. G., Munk-olsen, T., Benros, M. E., Als, T. D., Grove, J., Werge, T., Børglum, A. D., Hougaard, D. M., Mors, O., Nordentoft, M., ... Webb, T. (2023). Polygenic liability, stressful life events and risk for secondary-treated depression in early life: A nationwide register-based case-cohort study. Psychological Medicine, 53(1), 217-226. Article PII S0033291721001410. https://doi.org/10.1017/s0033291721001410
Background In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark. Methods Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions. Results Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (beta = -0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15. Conclusions These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.