Do shared genetic factors explain the prediction of bipolar disorder by childhood psychiatric symptoms?

Abstract

Adult psychiatric disorders can be preceded by a broad range of childhood psychiatric symptoms. For schizophrenia, it has been suggested that this association is due to shared genetic risk factors. This is less well established for bipolar disorder. Given the large increase in genetic variants associated with bipolar disorder and the large increase in available genotypes in individuals with longitudinal data on childhood psychiatric symptoms, it is timely to test genetic associations. Comparing the genetic associations for several adult psychiatric and related traits is also of relevance, as there is a large overlap in genetic variants influencing these phenotypes. Polygenic risk scores (PRS) are calculated based on the most recent results from Genome-Wide Association Meta-Analyses for schizophrenia, depression, bipolar disorder, wellbeing, neuroticism, BMI, height, educational attainment and insomnia. These risk scores reflect an individual's genetic vulnerability for a particular trait. The associations between the different PRS with internalizing, ADHD and social problems measured between age 7 and age 18 will be analysed in the cohorts participating in the CAPICE consortium (http://www.capice-project.eu/), total N = ~40,000. Preliminary analyses in the Netherlands Twin Register showed significant genetic associations between bipolar disorder PRS and internalizing problems, but no significant predictions for ADHD and social problems. This pattern of results was similar to the effects of schizophrenia PRS. In contrast, depression, neuroticism and wellbeing were also related to ADHD and social problems. Meta-regression analyses based on the results in all cohorts will also show whether these associations depend on age.L6271895182019-04-17 <br />