Anke Hüls1, Catherine J Wedderburn2,3,4, Nynke A Groenewold2,4,5,6, Nicole Gladish7,8,9, Meaghan J Jones10, Nastassja Koen4,5,11, Julia L MacIsaac7,8,9, David T S Lin7,8,9, Katia E Ramadori7,8,9, Michael P Epstein12, Kirsten A Donald2,4, Michael S Kobor7,8,9, Heather J Zar2,6, Dan J Stein4,5,11. 1. Department of Epidemiology and Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 2. Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa. 3. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. 4. Neuroscience Institute, University of Cape Town, Cape Town, South Africa. 5. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. 6. South African Medical Research Council (SAMRC) Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa. 7. Department of Medical Genetics, University of British Columbia, Vancouver, Canada. 8. BC Children's Hospital Research Institute, Vancouver, Canada. 9. Centre for Molecular Medicine and Therapeutics, Vancouver, Canada. 10. Department of Biochemistry and Medical Genetics, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, Canada. 11. South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa. 12. Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
Abstract
OBJECTIVES: Early detection of neurodevelopmental delay is crucial for intervention and treatment strategies. We analysed associations between newborn DNA methylation (DNAm), neonatal magnetic resonance imaging (MRI) neuroimaging data, and neurodevelopment. METHODS: Neurodevelopment was assessed in 161 children from the South African Drakenstein Child Health Study at 2 years of age using the Bayley Scales of Infant and Toddler Development III. We performed an epigenome-wide association study of neurodevelopmental delay using DNAm from cord blood. Subsequently, we analysed if associations between DNAm and neurodevelopmental delay were mediated by altered neonatal brain volumes (subset of 51 children). RESULTS: Differential DNAm at SPTBN4 (cg26971411, Δbeta = -0.024, p-value = 3.28 × 10-08), and two intergenic regions (chromosome 11: cg00490349, Δbeta = -0.036, p-value = 3.02 × 10-08; chromosome 17: cg15660740, Δbeta = -0.078, p-value = 6.49 × 10-08) were significantly associated with severe neurodevelopmental delay. While these associations were not mediated by neonatal brain volume, neonatal caudate volumes were independently associated with neurodevelopmental delay, particularly in language (Δcaudate volume = 165.30 mm3, p = 0.0443) and motor (Δcaudate volume = 365.36 mm3, p-value = 0.0082) domains. CONCLUSIONS: Differential DNAm from cord blood and increased neonatal caudate volumes were independently associated with severe neurodevelopmental delay at 2 years of age. These findings suggest that neurobiological signals for severe developmental delay may be detectable in very early life.
OBJECTIVES: Early detection of neurodevelopmental delay is crucial for intervention and treatment strategies. We analysed associations between newborn DNA methylation (DNAm), neonatal magnetic resonance imaging (MRI) neuroimaging data, and neurodevelopment. METHODS: Neurodevelopment was assessed in 161 children from the South African Drakenstein Child Health Study at 2 years of age using the Bayley Scales of Infant and Toddler Development III. We performed an epigenome-wide association study of neurodevelopmental delay using DNAm from cord blood. Subsequently, we analysed if associations between DNAm and neurodevelopmental delay were mediated by altered neonatal brain volumes (subset of 51 children). RESULTS: Differential DNAm at SPTBN4 (cg26971411, Δbeta = -0.024, p-value = 3.28 × 10-08), and two intergenic regions (chromosome 11: cg00490349, Δbeta = -0.036, p-value = 3.02 × 10-08; chromosome 17: cg15660740, Δbeta = -0.078, p-value = 6.49 × 10-08) were significantly associated with severe neurodevelopmental delay. While these associations were not mediated by neonatal brain volume, neonatal caudate volumes were independently associated with neurodevelopmental delay, particularly in language (Δcaudate volume = 165.30 mm3, p = 0.0443) and motor (Δcaudate volume = 365.36 mm3, p-value = 0.0082) domains. CONCLUSIONS: Differential DNAm from cord blood and increased neonatal caudate volumes were independently associated with severe neurodevelopmental delay at 2 years of age. These findings suggest that neurobiological signals for severe developmental delay may be detectable in very early life.
Entities:
Keywords:
Early child development; MRI imaging data; brain development; early biomarkers; methylome-wide association study
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