Using DNA to predict behaviour problems from preschool to adulthood

Abstract

BackgroundOne 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. MethodOur 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, externalizing and internalizing) across ages (from age 2 to age 21) and across raters in penalized 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. ResultsMulti-GPS prediction of behaviour problems increased from less than 2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability mirrored patterns of multi-GPS prediction as they increased from less than 40% to up to 83%. ConclusionsThe 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 results 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. Key pointsO_LIGenome-wide polygenic scores (GPS) can be used to predict behaviour problems in childhood, but the effect sizes are generally less than 3.5%. C_LIO_LIDNA-based prediction models of achieve greater accuracy if holistic approaches are employed, that is cross-trait, longitudinal and trans-situational approaches. C_LIO_LIThe prediction of childhood behaviour problems can be improved by using multiple GPS to predict composites that aggregate behaviour problems across ages and across raters. C_LIO_LIOur results yield weights that can be applied to GPS in any study to create multi-trait GPS predictors of behaviour problems based on cross-age and cross-rater composites. C_LIO_LIAs compared to individuals in the lowest multi-trait GPS decile, nearly three times as many individuals in the highest internalizing multi-trait GPS decile were diagnosed with anxiety disorder and 25% more individuals in the highest general behaviour problems and externalizing multi-trait GPS deciles have taken medication for mental health. C_LI