Integrative analysis of genomic and exposomic influences on youth mental health
Date
2022
Authors
Choi, K.W.
Wilson, M.
Ge, T.
Kandola, A.
Patel, C.J.
Lee, S.H.
Smoller, J.W.
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Journal article
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Journal of Child Psychology and Psychiatry, 2022; 63(10):1196-1205
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Abstract
Background Understanding complex influences on mental health problems in young people is needed to inform early prevention strategies. Both genetic and environmental factors are known to influence youth mental health, but a more comprehensive picture of their interplay, including wide-ranging environmental exposures - that is, the exposome - is needed. We perform an integrative analysis of genomic and exposomic data in relation to internalizing and externalizing symptoms in a cohort of 4,314 unrelated youth from the Adolescent Brain and Cognitive Development (ABCD) Study.
Methods Using novel GREML-based approaches, we model the variance in internalizing and externalizing symptoms explained by additive and interactive influences from the genome (G) and modeled exposome (E) consisting of up to 133 variables at the family, peer, school, neighborhood, life event, and broader environmental levels, including genome-by-exposome (G x E) and exposome-by-exposome (E x E) effects.
Results A best-fitting integrative model with G, E, and G x E components explained 35% and 63% of variance in youth internalizing and externalizing symptoms, respectively. Youth in the top quintile of model-predicted risk accounted for the majority of individuals with clinically elevated symptoms at follow-up (60% for internalizing; 72% for externalizing). Of note, different domains of environmental exposures were most impactful for internalizing (life events) and externalizing (contextual including family, school, and peer-level factors) symptoms. In addition, variance explained by G x E contributions was substantially larger for externalizing (33%) than internalizing (13%) symptoms.
Conclusions Advanced statistical genetic methods in a longitudinal cohort of youth can be leveraged to address fundamental questions about the role of 'nature and nurture' in developmental psychopathology.
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Data source: Supporting information, https://doi.org/10.1111/jcpp.13664
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Copyright 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. (http://creativecommons.org/licenses/by-nc-nd/4.0/)