Newborn differential DNA methylation and subcortical brain volumes as early signs of severe neurodevelopmental delay in a South African Birth Cohort Study.

Autor: Hüls A; Department of Epidemiology and Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Wedderburn CJ; Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.; Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Groenewold NA; Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.; South African Medical Research Council (SAMRC) Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa., Gladish N; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.; BC Children's Hospital Research Institute, Vancouver, Canada.; Centre for Molecular Medicine and Therapeutics, Vancouver, Canada., Jones MJ; Department of Biochemistry and Medical Genetics, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, Canada., Koen N; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.; South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa., MacIsaac JL; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.; BC Children's Hospital Research Institute, Vancouver, Canada.; Centre for Molecular Medicine and Therapeutics, Vancouver, Canada., Lin DTS; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.; BC Children's Hospital Research Institute, Vancouver, Canada.; Centre for Molecular Medicine and Therapeutics, Vancouver, Canada., Ramadori KE; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.; BC Children's Hospital Research Institute, Vancouver, Canada.; Centre for Molecular Medicine and Therapeutics, Vancouver, Canada., Epstein MP; Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA., Donald KA; Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.; Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Kobor MS; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.; BC Children's Hospital Research Institute, Vancouver, Canada.; Centre for Molecular Medicine and Therapeutics, Vancouver, Canada., Zar HJ; Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.; South African Medical Research Council (SAMRC) Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa., Stein DJ; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.; South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry [World J Biol Psychiatry] 2022 Oct; Vol. 23 (8), pp. 601-612. Date of Electronic Publication: 2022 Jan 12.
DOI: 10.1080/15622975.2021.2016955
Abstrakt: 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, Δ beta = -0.024, p -value = 3.28 × 10 -08 ), and two intergenic regions (chromosome 11: cg00490349, Δ beta = -0.036, p -value = 3.02 × 10 -08 ; chromosome 17: cg15660740, Δ beta = -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 ( Δ caudate volume = 165.30 mm 3 , p  = 0.0443) and motor ( Δ caudate volume = 365.36 mm 3 , 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje