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Genetics of co-developing conduct and emotional problems during childhood and adolescence

Nature Human Behaviour volume 2, pages 514–521 (2018)Cite this article

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Abstract

Common genetic influences offer a partial explanation for comorbidity between different psychiatric disorders1,2,3. However, the genetics underlying co-development—the cross-domain co-occurrence of patterns of change over time—of psychiatric symptoms during childhood and adolescence has not been well explored. Here, we show genetic influence on joint symptom trajectories of parent-reported conduct and emotional problems (overall N = 15,082) across development (4–16 years) using both twin- and genome-wide polygenic score analyses (genotyped N = 2,610). Specifically, we found seven joint symptom trajectories, including two characterized by jointly stable and jointly increasing symptoms of conduct and emotional problems, respectively (7.3% of the sample, collectively). Twin modelling analyses revealed substantial genetic influence on trajectories (heritability estimates range of 0.41–0.78). Furthermore, individuals’ risk of being classified in the most symptomatic trajectory classes was significantly predicted by polygenic scores for years-of-education-associated alleles and depressive symptoms-associated alleles. Complementary analyses of child self-reported symptoms across late childhood and early adolescence yielded broadly similar results. Taken together, our results indicate that genetic factors are involved in the co-development of conduct and emotional problems across childhood and adolescence, and that individuals with co-developing symptoms across multiple domains may represent a clinical subgroup characterized by increased levels of genetic risk.

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Fig. 1: Joint trajectory latent class growth model for parent-reported symptoms of conduct and emotional problems with intercept and linear and quadratic slopes.
Fig. 2: Joint developmental trajectory classes of parent-reported symptoms of conduct and emotional problems from the best-fitting 7-class model.
Fig. 3: Distribution of education years and depressive symptoms GPS among each of the seven joint developmental trajectory classes of parent-reported symptoms of conduct and emotional problems.

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Acknowledgements

We gratefully acknowledge the ongoing contribution of the participants in the TEDS and their families. TEDS is supported by a programme grant 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 and 295366). L.J.H. is supported by a 1 + 3 PhD studentship from the UK Economic and Social Research Council (ESRC). J.-B.P. is a fellow of MQ: Transforming Mental Health. E.K. is supported by the MRC/IoPPN Excellence Award. T.A.M. is supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (107706/Z/15/Z). This study presents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank R. Plomin for his input and advice.

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  1. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Laurie J. Hannigan, Jean-Baptiste Pingault, Eva Krapohl, Tom A. McAdams, Frühling V. Rijsdijk & Thalia C. Eley

  2. Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

    Laurie J. Hannigan

  3. Division of Psychology and Language Sciences, University College London, London, UK

    Jean-Baptiste Pingault

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Contributions

L.J.H., T.C.E., T.A.M. and F.V.R. conceived of the investigation. L.J.H., J.-B.P. and E.K. discussed the analytic strategy, and L.J.H. and E.K. carried out the statistical analyses. L.J.H., T.C.E., T.A.M. and F.V.R. worked on interpreting the results and refining the analyses. L.J.H. wrote the manuscript, and all authors critically reviewed the manuscript.

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Correspondence to Thalia C. Eley.

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Hannigan, L.J., Pingault, JB., Krapohl, E. et al. Genetics of co-developing conduct and emotional problems during childhood and adolescence. Nat Hum Behav 2, 514–521 (2018). https://doi.org/10.1038/s41562-018-0373-9

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