Polygenic risk for schizophrenia, social dispositions, and pace of epigenetic aging: Results from the Young Finns Study

Abstract

<p>Schizophrenia is often regarded as a disorder of premature aging. We investigated (a) whether polygenic risk for schizophrenia (PRS<sub>sch</sub>) relates to pace of epigenetic aging and (b) whether personal dispositions toward active and emotionally close relationships protect against accelerated epigenetic aging in individuals with high PRS<sub>sch</sub>. The sample came from the population-based Young Finns Study (n = 1348). Epigenetic aging was measured with DNA methylation aging algorithms such as AgeAccel<sub>Hannum</sub>, EEAA<sub>Hannum</sub>, IEAA<sub>Hannum</sub>, IEAA<sub>Horvath</sub>, AgeAccel<sub>Horvath</sub>, AgeAccel<sub>Pheno</sub>, AgeAccel<sub>Grim</sub>, and DunedinPACE. A PRS<sub>sch</sub> was calculated using summary statistics from the most comprehensive genome-wide association study of schizophrenia to date. Social dispositions were assessed in terms of extraversion, sociability, reward dependence, cooperativeness, and attachment security. We found that PRS<sub>sch</sub> did not have a statistically significant effect on any studied indicator of epigenetic aging. Instead, PRS<sub>sch</sub> had a significant interaction with reward dependence (p = 0.001–0.004), cooperation (p = 0.009–0.020), extraversion (p = 0.019–0.041), sociability (p = 0.003–0.016), and attachment security (p = 0.007–0.014) in predicting AgeAccel<sub>Hannum</sub>, EEAA<sub>Hannum</sub>, or IEAA<sub>Hannum</sub>. Specifically, participants with high PRS<sub>sch</sub> appeared to display accelerated epigenetic aging at higher (vs. lower) levels of extraversion, sociability, attachment security, reward dependence, and cooperativeness. A rather opposite pattern was evident for those with low PRS<sub>sch</sub>. No such interactions were evident when predicting the other indicators of epigenetic aging. In conclusion, against our hypothesis, frequent social interactions may relate to accelerated epigenetic aging in individuals at risk for psychosis. We speculate that this may be explained by social-cognitive impairments (perceiving social situations as overwhelming or excessively arousing) or ending up in less supportive or deviant social groups.</p>