Background: One goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems. Method: Our sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems, and peer problems as rated by parents, teachers, and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalising, and internalising) across ages (from age 2 to 21) and across raters in penalised regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures. Results: Multi-GPS prediction of behaviour problems increased from <2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability, although to a lesser extent, mirrored patterns of multi-GPS prediction as they increased from <40% to 83%. Conclusions: The ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our approach can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater, or GPS.
|Journal||Journal of Child Psychology and Psychiatry and Allied Disciplines|
|Early online date||6 Sept 2021|
|Publication status||Published - Jul 2022|
Bibliographical noteFunding Information:
The authors gratefully acknowledge the on‐going contribution of the participants in the TEDS and their families. TEDS is supported by a programme grant to R.P. from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938) and the European Commission (602768; 295366). The authors have declared that they have no competing or potential conflicts of interest. Key points
© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.
- Behaviour problems
- polygenic scores
- twin study