Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context
Summary: Background: The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways. Methods: In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mas...
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Elsevier
2025-03-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000234 |
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| author | Jian Huang Jinyi Che Michelle Z.L. Kee Ai Peng Tan Evelyn C. Law Patricia Pelufo Silveira Irina Pokhvisneva Sachin Patel Keith M. Godfrey Lourdes Mary Daniel Kok Hian Tan Yap Seng Chong Shiao-Yng Chan Johan G. Eriksson Dennis Wang Jonathan Yinhao Huang |
| author_facet | Jian Huang Jinyi Che Michelle Z.L. Kee Ai Peng Tan Evelyn C. Law Patricia Pelufo Silveira Irina Pokhvisneva Sachin Patel Keith M. Godfrey Lourdes Mary Daniel Kok Hian Tan Yap Seng Chong Shiao-Yng Chan Johan G. Eriksson Dennis Wang Jonathan Yinhao Huang |
| author_sort | Jian Huang |
| collection | DOAJ |
| description | Summary: Background: The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways. Methods: In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mass index (BMI) to interrogate the causal effects of early-life BMI on child language development and its effects on molecular and neuroimaging measures. Leveraging large genome-wide association studies, we examined whether the link between obesity and language development is causal or due to a shared genetic basis. Findings: We found an inverse association between polygenic risk for obesity, which is less susceptible to confounding, and language ability assessed at age 9. Our findings suggested a shared genetic basis between obesity and language development rather than a causal effect of obesity on language development. Interrogating early-life mechanisms including neurology-related proteomics and language-related white matter microstructure, we found that EFNA4 and VWC2 expressions were associated with language ability as well as fractional anisotropy of language-related white matter tracts, suggesting a role in brain myelination. Additionally, the expression of the EPH-Ephrin signalling pathway in the hippocampus might contribute to language development. Polygenic risk for obesity was nominally associated with EFNA4 and VWC2 expression. However, we did not find support for mediating mechanisms via these proteins. Interpretation: This study demonstrates the potential of examining early-life proteomics in conjunction with deep genotyping and phenotyping and provides biological insights into the shared genomic links between obesity and language development. Funding: Singapore National Research Foundation and Agency for Science, Technology and Research. |
| format | Article |
| id | doaj-art-16caa388f8b440499b8d0e6d5983a586 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-16caa388f8b440499b8d0e6d5983a5862025-02-12T05:31:18ZengElsevierEBioMedicine2352-39642025-03-01113105579Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in contextJian Huang0Jinyi Che1Michelle Z.L. Kee2Ai Peng Tan3Evelyn C. Law4Patricia Pelufo Silveira5Irina Pokhvisneva6Sachin Patel7Keith M. Godfrey8Lourdes Mary Daniel9Kok Hian Tan10Yap Seng Chong11Shiao-Yng Chan12Johan G. Eriksson13Dennis Wang14Jonathan Yinhao Huang15Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Bioinformatics Institute, Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Human Potential Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK; Corresponding author. Institute for Human Development and Potential (IHDP), Brenner Centre for Molecular Medicine, 30 Medical Drive, 117609, Republic of Singapore.Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Bioinformatics Institute, Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Republic of SingaporeInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of SingaporeInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Department of Diagnostic Imaging, National University Hospital, Singapore, Republic of Singapore; Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, NUS, Singapore, Republic of SingaporeInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Republic of SingaporeDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; Department of Psychiatry, Faculty of Medicine and Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, Montreal, CanadaDepartment of Psychiatry, Faculty of Medicine and Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, Montreal, CanadaDepartment of Psychiatry, Faculty of Medicine and Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, Montreal, CanadaMRC Lifecourse Epidemiology Centre and NIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, United KingdomDepartment of Child Development, KK Women's and Children's Hospital, Singapore, Republic of SingaporeDepartment of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Republic of SingaporeInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of SingaporeInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Human Potential Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of SingaporeInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Human Potential Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, FinlandInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Bioinformatics Institute, Agency for Science, Technology and Research (A∗STAR), Singapore, Republic of Singapore; Human Potential Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore; National Heart and Lung Institute, Imperial College London, London, UK; Department of Computer Science, University of Sheffield, Sheffield, UKCentre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Republic of Singapore; Thompson School of Social Work & Public Health, Office of Public Health Studies, University of Hawai'i at Mānoa, Honolulu, Hawaii, USASummary: Background: The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways. Methods: In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mass index (BMI) to interrogate the causal effects of early-life BMI on child language development and its effects on molecular and neuroimaging measures. Leveraging large genome-wide association studies, we examined whether the link between obesity and language development is causal or due to a shared genetic basis. Findings: We found an inverse association between polygenic risk for obesity, which is less susceptible to confounding, and language ability assessed at age 9. Our findings suggested a shared genetic basis between obesity and language development rather than a causal effect of obesity on language development. Interrogating early-life mechanisms including neurology-related proteomics and language-related white matter microstructure, we found that EFNA4 and VWC2 expressions were associated with language ability as well as fractional anisotropy of language-related white matter tracts, suggesting a role in brain myelination. Additionally, the expression of the EPH-Ephrin signalling pathway in the hippocampus might contribute to language development. Polygenic risk for obesity was nominally associated with EFNA4 and VWC2 expression. However, we did not find support for mediating mechanisms via these proteins. Interpretation: This study demonstrates the potential of examining early-life proteomics in conjunction with deep genotyping and phenotyping and provides biological insights into the shared genomic links between obesity and language development. Funding: Singapore National Research Foundation and Agency for Science, Technology and Research.http://www.sciencedirect.com/science/article/pii/S2352396425000234Polygenic risk scoreObesityLanguage developmentNeurology-related protein |
| spellingShingle | Jian Huang Jinyi Che Michelle Z.L. Kee Ai Peng Tan Evelyn C. Law Patricia Pelufo Silveira Irina Pokhvisneva Sachin Patel Keith M. Godfrey Lourdes Mary Daniel Kok Hian Tan Yap Seng Chong Shiao-Yng Chan Johan G. Eriksson Dennis Wang Jonathan Yinhao Huang Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context EBioMedicine Polygenic risk score Obesity Language development Neurology-related protein |
| title | Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context |
| title_full | Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context |
| title_fullStr | Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context |
| title_full_unstemmed | Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context |
| title_short | Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelinationResearch in context |
| title_sort | linking obesity associated genotype to child language development the role of early life neurology related proteomics and brain myelinationresearch in context |
| topic | Polygenic risk score Obesity Language development Neurology-related protein |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000234 |
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