Changes in polygenic burden for psychiatric disorders across two decades of birth cohorts

During recent decades, the incidence of several psychiatric disorders has increased, but no previous study has investigated whether the polygenic burden based on common variants for psychiatric disorders in diagnosed individuals has changed over time. Here we aimed to explore changes in polygenic scores for schizophrenia, depression, autism and attention deficit hyperactivity disorder (ADHD) in the general population and in case populations according to birth cohorts. The iPSYCH2015 is a Danish population-based case–cohort study, including individuals born between 1981 and 2008, who were followed for a psychiatric diagnosis between 1994 and 2015. We included 41,132 individuals from the random subcohort and 60,293 individuals diagnosed with schizophrenia spectrum disorders, depression, autism or ADHD. We estimated changes in polygenic scores across birth years based on linear regression. The average polygenic score was stable in the random subcohort but decreased across birth years in case populations, most predominantly for schizophrenia (per 10 years: −0.13 s.d., 95% confidence interval (CI) −0.18 to −0.07) but also for depression (−0.06 s.d., 95% CI −0.10 to −0.03) and autism (−0.08 s.d., 95% CI −0.13 to −0.04) and to a limited degree for ADHD (−0.03 s.d., 95% CI −0.08 to 0.02). Moreover, we estimated how the hazard ratio for being diagnosed given a 1 s.d. increase in polygenic score changed according to birth year, which decreased for schizophrenia but remained stable for the other disorders. Finally, we estimated the number of additional cases per 1 s.d. increase in polygenic score according to birth year, which decreased for both schizophrenia and depression, whereas autism and ADHD showed increases. In conclusion, the polygenic burden for psychiatric disorders changed across two decades among diagnosed individuals in Denmark. For schizophrenia, the polygenic score itself and its predictive ability decreased over time, whereas depression, autism and ADHD showed diverse changes. Lousdal et al. investigate the changes in polygenic scores for schizophrenia, depression, autism and attention deficit hyperactivity disorder using data from a Danish population-based case–cohort study that includes individuals born between 1981 and 2008.