Molecular mediators of the association between child obesity and mental health
Biological mechanisms underlying the association between obesity and depression remain unclear. We investigated the role of metabolites and DNA methylation as mediators of the relationship between childhood obesity and subsequent poor mental health in the English Avon Longitudinal Study of Parents a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.947591/full |
| _version_ | 1817983882303111168 |
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| author | Evangelos Handakas Yiwen Xu Alexa Blair Segal Maria Carmen Huerta Kirsty Bowman Kirsty Bowman Laura D. Howe Laura D. Howe Franco Sassi Oliver Robinson |
| author_facet | Evangelos Handakas Yiwen Xu Alexa Blair Segal Maria Carmen Huerta Kirsty Bowman Kirsty Bowman Laura D. Howe Laura D. Howe Franco Sassi Oliver Robinson |
| author_sort | Evangelos Handakas |
| collection | DOAJ |
| description | Biological mechanisms underlying the association between obesity and depression remain unclear. We investigated the role of metabolites and DNA methylation as mediators of the relationship between childhood obesity and subsequent poor mental health in the English Avon Longitudinal Study of Parents and Children. Obesity was defined according to United Kingdom Growth charts at age 7 years and mental health through the Short Mood and Feelings Questionnaire (SMFQ) completed at age 11 years. Metabolites and DNA methylation were measured by nuclear magnetic resonance spectroscopy and Illumina array in blood at the age of 7 years. The associations between obesity and SMFQ score, as continuous count data or using cut-offs to define depressive symptoms (SMFQ >7) or depression (SMFQ >11), were tested using adjusted Poisson and logistic regression. Candidate metabolite mediators were identified through metabolome-wide association scans for obesity and SMFQ score, correcting for false-discovery rate. Candidate DNA methylation mediators were identified through testing the association of putative BMI-associated CpG sites with SMFQ scores, correcting for look-up false-discovery rate. Mediation by candidate molecular markers was tested. Two-sample Mendelian randomization (MR) analyses were additionally applied to test causal associations of metabolites with depression in independent adult samples. 4,018 and 768 children were included for metabolomics and epigenetics analyses, respectively. Obesity at 7 years was associated with a 14% increase in SMFQ score (95% CI: 1.04, 1.25) and greater odds of depression (OR: 1.46 (95% CI: 0.78, 2.38) at 11 years. Natural indirect effects (mediating pathways) between obesity and depression for tyrosine, leucine and conjugated linoleic acid were 1.06 (95% CI: 1.00, 1.13, proportion mediated (PM): 15%), 1.04 (95% CI: 0.99, 1.10, PM: 9.6%) and 1.06 (95% CI: 1.00, 1.12, PM: 13.9%) respectively. In MR analysis, one unit increase in tyrosine was associated with 0.13 higher log odds of depression (p = 0.1). Methylation at cg17128312, located in the FBXW9 gene, had a natural indirect effect of 1.05 (95% CI: 1.01,1.13, PM: 27%) as a mediator of obesity and SMFQ score. Potential biologically plausible mechanisms involving these identified molecular features include neurotransmitter regulation, inflammation, and gut microbiome modulation. These results require replication in further observational and mechanistic studies. |
| first_indexed | 2024-04-13T23:38:30Z |
| format | Article |
| id | doaj.art-f6932770b52b4da187a8120976fc7058 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T23:38:30Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-f6932770b52b4da187a8120976fc70582022-12-22T02:24:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.947591947591Molecular mediators of the association between child obesity and mental healthEvangelos Handakas0Yiwen Xu1Alexa Blair Segal2Maria Carmen Huerta3Kirsty Bowman4Kirsty Bowman5Laura D. Howe6Laura D. Howe7Franco Sassi8Oliver Robinson9Μedical Research Council Centre for Environment and Health, Imperial College London, London, United KingdomCentre for Health Economics and Policy Innovation, Department of Economics and Public Policy, Imperial College Business School, London, United KingdomCentre for Health Economics and Policy Innovation, Department of Economics and Public Policy, Imperial College Business School, London, United KingdomCentre for Health Economics and Policy Innovation, Department of Economics and Public Policy, Imperial College Business School, London, United KingdomMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United KingdomPopulation Health Sciences, University of Bristol, Bristol, United KingdomMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United KingdomPopulation Health Sciences, University of Bristol, Bristol, United KingdomCentre for Health Economics and Policy Innovation, Department of Economics and Public Policy, Imperial College Business School, London, United KingdomΜedical Research Council Centre for Environment and Health, Imperial College London, London, United KingdomBiological mechanisms underlying the association between obesity and depression remain unclear. We investigated the role of metabolites and DNA methylation as mediators of the relationship between childhood obesity and subsequent poor mental health in the English Avon Longitudinal Study of Parents and Children. Obesity was defined according to United Kingdom Growth charts at age 7 years and mental health through the Short Mood and Feelings Questionnaire (SMFQ) completed at age 11 years. Metabolites and DNA methylation were measured by nuclear magnetic resonance spectroscopy and Illumina array in blood at the age of 7 years. The associations between obesity and SMFQ score, as continuous count data or using cut-offs to define depressive symptoms (SMFQ >7) or depression (SMFQ >11), were tested using adjusted Poisson and logistic regression. Candidate metabolite mediators were identified through metabolome-wide association scans for obesity and SMFQ score, correcting for false-discovery rate. Candidate DNA methylation mediators were identified through testing the association of putative BMI-associated CpG sites with SMFQ scores, correcting for look-up false-discovery rate. Mediation by candidate molecular markers was tested. Two-sample Mendelian randomization (MR) analyses were additionally applied to test causal associations of metabolites with depression in independent adult samples. 4,018 and 768 children were included for metabolomics and epigenetics analyses, respectively. Obesity at 7 years was associated with a 14% increase in SMFQ score (95% CI: 1.04, 1.25) and greater odds of depression (OR: 1.46 (95% CI: 0.78, 2.38) at 11 years. Natural indirect effects (mediating pathways) between obesity and depression for tyrosine, leucine and conjugated linoleic acid were 1.06 (95% CI: 1.00, 1.13, proportion mediated (PM): 15%), 1.04 (95% CI: 0.99, 1.10, PM: 9.6%) and 1.06 (95% CI: 1.00, 1.12, PM: 13.9%) respectively. In MR analysis, one unit increase in tyrosine was associated with 0.13 higher log odds of depression (p = 0.1). Methylation at cg17128312, located in the FBXW9 gene, had a natural indirect effect of 1.05 (95% CI: 1.01,1.13, PM: 27%) as a mediator of obesity and SMFQ score. Potential biologically plausible mechanisms involving these identified molecular features include neurotransmitter regulation, inflammation, and gut microbiome modulation. These results require replication in further observational and mechanistic studies.https://www.frontiersin.org/articles/10.3389/fgene.2022.947591/fullchildobesitydepressionmultiomicsALSPAC |
| spellingShingle | Evangelos Handakas Yiwen Xu Alexa Blair Segal Maria Carmen Huerta Kirsty Bowman Kirsty Bowman Laura D. Howe Laura D. Howe Franco Sassi Oliver Robinson Molecular mediators of the association between child obesity and mental health Frontiers in Genetics child obesity depression multiomics ALSPAC |
| title | Molecular mediators of the association between child obesity and mental health |
| title_full | Molecular mediators of the association between child obesity and mental health |
| title_fullStr | Molecular mediators of the association between child obesity and mental health |
| title_full_unstemmed | Molecular mediators of the association between child obesity and mental health |
| title_short | Molecular mediators of the association between child obesity and mental health |
| title_sort | molecular mediators of the association between child obesity and mental health |
| topic | child obesity depression multiomics ALSPAC |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.947591/full |
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