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Integrative analysis of genomic and exposomic influences on youth mental health

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dc.contributor.authorChoi, K.W.
dc.contributor.authorWilson, M.
dc.contributor.authorGe, T.
dc.contributor.authorKandola, A.
dc.contributor.authorPatel, C.J.
dc.contributor.authorLee, S.H.
dc.contributor.authorSmoller, J.W.
dc.date.issued2022
dc.descriptionData source: Supporting information, https://doi.org/10.1111/jcpp.13664
dc.description.abstractBackground 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.
dc.identifier.citationJournal of Child Psychology and Psychiatry, 2022; 63(10):1196-1205
dc.identifier.doi10.1111/jcpp.13664
dc.identifier.issn0021-9630
dc.identifier.issn1469-7610
dc.identifier.urihttps://hdl.handle.net/11541.2/30520
dc.language.isoen
dc.publisherWiley-Blackwell Publishing
dc.relation.fundingNational Institute of Mental Health K08MH127413
dc.relation.fundingKaplen Fellowship on Depression from the Harvard Medical School
dc.relation.fundingNARSAD Young Investigator Grant from the Brain & Behavior Research Foundation
dc.relation.fundingDemarest Lloyd Jr. Foundation
dc.relation.fundingTommy Fuss Fund
dc.relation.fundingNational Institutes of Health U01DA041048
dc.relation.fundingNational Institutes of Health U01DA050989
dc.relation.fundingNational Institutes of Health U01DA051016
dc.relation.fundingNational Institutes of Health U01DA041022
dc.relation.fundingNational Institutes of Health U01DA051018
dc.relation.fundingNational Institutes of Health U01DA051037
dc.relation.fundingNational Institutes of Health U01DA050987
dc.relation.fundingNational Institutes of Health U01DA041174
dc.relation.fundingNational Institutes of Health U01DA041106
dc.relation.fundingNational Institutes of Health U01DA041117
dc.relation.fundingNational Institutes of Health U01DA041028
dc.relation.fundingNational Institutes of Health U01DA041134
dc.relation.fundingNational Institutes of Health U01DA050988
dc.relation.fundingNational Institutes of Health U01DA051039
dc.relation.fundingNational Institutes of Health U01DA041156
dc.relation.fundingNational Institutes of Health U01DA041025
dc.relation.fundingNational Institutes of Health U01DA041120
dc.relation.fundingNational Institutes of Health U01DA051038
dc.relation.fundingNational Institutes of Health U01DA041148
dc.relation.fundingNational Institutes of Health U01DA041093
dc.relation.fundingNational Institutes of Health U01DA041089
dc.relation.fundingNational Institutes of Health U24DA041123
dc.relation.fundingNational Institutes of Health U24DA041147
dc.rightsCopyright 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/)
dc.source.urihttps://doi.org/10.1111/jcpp.13664
dc.subjectexposome
dc.subjectgenetics
dc.subjectyouth mental health
dc.subjectdepression
dc.subjectgene-environment interaction
dc.subjectG x E
dc.subjectheritability
dc.titleIntegrative analysis of genomic and exposomic influences on youth mental health
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12250309530001831 13252299150001831 Child Psychology Psychiatry - 2022 - Choi - Integrative analysis of genomic and exposomic influences on youth mental health (1)
ror.mmsid9916674025201831

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