Dataset Information

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

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.

SUBMITTER: Huls A

PROVIDER: S-EPMC9273810 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Hüls Anke A Wedderburn Catherine J CJ Groenewold Nynke A NA Gladish Nicole N Jones Meaghan J MJ Koen Nastassja N MacIsaac Julia L JL Lin David T S DTS Ramadori Katia E KE Epstein Michael P MP Donald Kirsten A KA Kobor Michael S MS Zar Heather J HJ Stein Dan J DJ

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 20220112 8

<h4>Objectives</h4>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.<h4>Methods</h4>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 associat ...[more]

PMID: 34895032

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Project description:BackgroundExposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother to child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10 μm or less (PM10) was measured inside participants' homes during the second trimester of pregnancy.ResultsA total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM10 and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01, 0.86] for cg00694520 to 0.54 [0.11, 1.56] for cg05023582.ConclusionsOur findings suggest that DNAm may mediate the association between prenatal PM10 exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.

Project description:PurposeIn an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of aging. Thus, we investigated sex, age, and their interactions on subcortical volumes, including the basal ganglia (caudate, putamen, accumbens, and pallidum), thalamus, hippocampus, and amygdala.MethodsWe analyzed the adult lifespan trajectory of subcortical volumes and asymmetries in 563 healthy subjects aged from 19 to 86 using magnetic resonance imaging (MRI) data from the publicly available 7IXI data set.ResultsThe sex made strong contributions to the trajectories of subcortical volumes with aging, including the right putamen, right pallidum, bilateral thalamus, hippocampus, and amygdala. The volume of the right putamen, right pallidum, and right thalamus decreased more rapidly in males than in females, and the volume of the left thalamus, bilateral hippocampus, and amygdala in males followed a quadratic model, while those in females followed a linear decline model. The asymmetries in the caudate and hippocampus showed a linear decline, and a sex and age interaction was found in the hippocampus; that is, the asymmetry in the hippocampus decreased only in the males and not in the females. Changes in the accumbens and pallidum fit quadratic trajectories, in which females increased until 39.26 years old in the accumbens asymmetry and then began to rapidly decline, and males showed a linear decline. The asymmetry in the pallidum in males and females showed a slow decreasing period until almost 45 years of age and then increased.ConclusionThe results suggest that compared with females, males have a faster decline in the volume of the right putamen, right pallidum, and right thalamus, while aging occurred later but also faster in the left thalamus, bilateral hippocampus, and amygdala. Interestingly, we found the inflection point in the thalamus, bilateral hippocampus, and amygdala volume in the quadratic model, and after this point, the volume change accelerated with aging, which may have resulted from the stronger work pressure in the middle-aged men and the low levels of testosterone in the older adults. The interaction of age and sex on individual subcortical structures provides evidence to support the impact of sex on psychopathologies associated with degenerative brain disorders in the elderly. The findings may be significant to investigate the occurrence and prevalence of degenerative brain disorders in males and females. Future studies can focus on the functional and behavioral relations with subcortical structures for preventive measures of related disorders.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

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