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Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour.

Lillycrop KA, Costello PM, Teh AL, Murray RJ, Clarke-Harris R, Barton SJ, Garratt ES, Ngo S, Sheppard AM, Wong J, Dogra S, Burdge GC, Cooper C, Inskip HM, Gale CR, Gluckman PD, Harvey NC, Chong YS, Yap F, Meaney MJ, Rifkin-Graboi A, Holbrook JD, Epigen Global Research ConsortiumGodfrey KM - Int J Epidemiol (2015)

Bottom Line: Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS 7-year-olds.Here, HES1 DMROI methylation predicted differences in early infant behaviour, known to be associated with academic success.Thus, our findings suggest that perinatal epigenetic processes mark later neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biological Sciences, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK, kal@soton.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Methylation of HES1 DMR in cord at birth is associated with WPPSI IQ at 4 years of age. a) Manhattan plot of epigenome-wide methylation analysis. The X-axis indicates chromosomal position, the Y-axis the –log 10 P-value of the Fishers Exact test. The black dots represent DMROIs and those associated with HES1, NR4A2, ETS1 and TCF4 are shown in red. b) Diencephalon development pathway. Genes contained in the diencephalon development GO process were connected to each other by using the direct interactions algorithm in GeneGoMetacoreTM. Genes containing DMROIs (HES1, NURR1, ETS1 and TCF4) are denoted by green circles (NR4A2 is denoted by its alternative name NURR1). This figure is generated in Cytoscape. c) DMROI plot for HES1 (Chr 3: 193848528–193853872). X-axis shows chromosomal coordinates (hg19), Y-axis shows absolute % methylation difference between WPSSI Groups 1 and 4. Green and red circles represent start and end of each 100-nucleotide region returned from BATMAN, respectively; 100 nucleotide regions in the dotted box were found to have >20% absolute methylation difference between WPSSI Groups 1 and 4 and this region was selected for pyrosequencing in the extended sample set. The lower panel shows the positions of the HES1 transcript and the upstream DMROI. d) Concordance of methylation values with WPSSI scores for the 100-nt region within the HES1 ROI selected for pyrosequencing (containing CpGs 2–8), upstream of the HES1 coding sequence. X-axis shows WPSSI scores and Y-axis shows % methylation as estimated by the Bayesian algorithm BATMAN. Sample data points are coloured by WPSSI groups (red = Group 1, lowest WPSSI scores; blue = Group 2, low WPSSI scores; green = Group 3, high WPSSI scores; yellow = Group 4, highest WPSSI scores). Chromosomal coordinates of the region are detailed above the figure. WPPSI = Wechsler Pre-School and Primary Scale of Intelligence (full-scale IQ).
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dyv052-F2: Methylation of HES1 DMR in cord at birth is associated with WPPSI IQ at 4 years of age. a) Manhattan plot of epigenome-wide methylation analysis. The X-axis indicates chromosomal position, the Y-axis the –log 10 P-value of the Fishers Exact test. The black dots represent DMROIs and those associated with HES1, NR4A2, ETS1 and TCF4 are shown in red. b) Diencephalon development pathway. Genes contained in the diencephalon development GO process were connected to each other by using the direct interactions algorithm in GeneGoMetacoreTM. Genes containing DMROIs (HES1, NURR1, ETS1 and TCF4) are denoted by green circles (NR4A2 is denoted by its alternative name NURR1). This figure is generated in Cytoscape. c) DMROI plot for HES1 (Chr 3: 193848528–193853872). X-axis shows chromosomal coordinates (hg19), Y-axis shows absolute % methylation difference between WPSSI Groups 1 and 4. Green and red circles represent start and end of each 100-nucleotide region returned from BATMAN, respectively; 100 nucleotide regions in the dotted box were found to have >20% absolute methylation difference between WPSSI Groups 1 and 4 and this region was selected for pyrosequencing in the extended sample set. The lower panel shows the positions of the HES1 transcript and the upstream DMROI. d) Concordance of methylation values with WPSSI scores for the 100-nt region within the HES1 ROI selected for pyrosequencing (containing CpGs 2–8), upstream of the HES1 coding sequence. X-axis shows WPSSI scores and Y-axis shows % methylation as estimated by the Bayesian algorithm BATMAN. Sample data points are coloured by WPSSI groups (red = Group 1, lowest WPSSI scores; blue = Group 2, low WPSSI scores; green = Group 3, high WPSSI scores; yellow = Group 4, highest WPSSI scores). Chromosomal coordinates of the region are detailed above the figure. WPPSI = Wechsler Pre-School and Primary Scale of Intelligence (full-scale IQ).

Mentions: Genomic umbilical cord DNA from 24 SWS children was screened using the MBD array for differences in DNA methylation at birth associated with WPPSI IQ age 4 years (Figure 1). The subjects selected were representative of the range of WPPSI IQ measurements within the whole cohort. Statistical analysis of the data identified 41 DMROIs associated with IQ at age 4 years (Supplementary Table 4, available as Supplementary data at IJE online; Figure 2a).Figure 1.


Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour.

Lillycrop KA, Costello PM, Teh AL, Murray RJ, Clarke-Harris R, Barton SJ, Garratt ES, Ngo S, Sheppard AM, Wong J, Dogra S, Burdge GC, Cooper C, Inskip HM, Gale CR, Gluckman PD, Harvey NC, Chong YS, Yap F, Meaney MJ, Rifkin-Graboi A, Holbrook JD, Epigen Global Research ConsortiumGodfrey KM - Int J Epidemiol (2015)

Methylation of HES1 DMR in cord at birth is associated with WPPSI IQ at 4 years of age. a) Manhattan plot of epigenome-wide methylation analysis. The X-axis indicates chromosomal position, the Y-axis the –log 10 P-value of the Fishers Exact test. The black dots represent DMROIs and those associated with HES1, NR4A2, ETS1 and TCF4 are shown in red. b) Diencephalon development pathway. Genes contained in the diencephalon development GO process were connected to each other by using the direct interactions algorithm in GeneGoMetacoreTM. Genes containing DMROIs (HES1, NURR1, ETS1 and TCF4) are denoted by green circles (NR4A2 is denoted by its alternative name NURR1). This figure is generated in Cytoscape. c) DMROI plot for HES1 (Chr 3: 193848528–193853872). X-axis shows chromosomal coordinates (hg19), Y-axis shows absolute % methylation difference between WPSSI Groups 1 and 4. Green and red circles represent start and end of each 100-nucleotide region returned from BATMAN, respectively; 100 nucleotide regions in the dotted box were found to have >20% absolute methylation difference between WPSSI Groups 1 and 4 and this region was selected for pyrosequencing in the extended sample set. The lower panel shows the positions of the HES1 transcript and the upstream DMROI. d) Concordance of methylation values with WPSSI scores for the 100-nt region within the HES1 ROI selected for pyrosequencing (containing CpGs 2–8), upstream of the HES1 coding sequence. X-axis shows WPSSI scores and Y-axis shows % methylation as estimated by the Bayesian algorithm BATMAN. Sample data points are coloured by WPSSI groups (red = Group 1, lowest WPSSI scores; blue = Group 2, low WPSSI scores; green = Group 3, high WPSSI scores; yellow = Group 4, highest WPSSI scores). Chromosomal coordinates of the region are detailed above the figure. WPPSI = Wechsler Pre-School and Primary Scale of Intelligence (full-scale IQ).
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dyv052-F2: Methylation of HES1 DMR in cord at birth is associated with WPPSI IQ at 4 years of age. a) Manhattan plot of epigenome-wide methylation analysis. The X-axis indicates chromosomal position, the Y-axis the –log 10 P-value of the Fishers Exact test. The black dots represent DMROIs and those associated with HES1, NR4A2, ETS1 and TCF4 are shown in red. b) Diencephalon development pathway. Genes contained in the diencephalon development GO process were connected to each other by using the direct interactions algorithm in GeneGoMetacoreTM. Genes containing DMROIs (HES1, NURR1, ETS1 and TCF4) are denoted by green circles (NR4A2 is denoted by its alternative name NURR1). This figure is generated in Cytoscape. c) DMROI plot for HES1 (Chr 3: 193848528–193853872). X-axis shows chromosomal coordinates (hg19), Y-axis shows absolute % methylation difference between WPSSI Groups 1 and 4. Green and red circles represent start and end of each 100-nucleotide region returned from BATMAN, respectively; 100 nucleotide regions in the dotted box were found to have >20% absolute methylation difference between WPSSI Groups 1 and 4 and this region was selected for pyrosequencing in the extended sample set. The lower panel shows the positions of the HES1 transcript and the upstream DMROI. d) Concordance of methylation values with WPSSI scores for the 100-nt region within the HES1 ROI selected for pyrosequencing (containing CpGs 2–8), upstream of the HES1 coding sequence. X-axis shows WPSSI scores and Y-axis shows % methylation as estimated by the Bayesian algorithm BATMAN. Sample data points are coloured by WPSSI groups (red = Group 1, lowest WPSSI scores; blue = Group 2, low WPSSI scores; green = Group 3, high WPSSI scores; yellow = Group 4, highest WPSSI scores). Chromosomal coordinates of the region are detailed above the figure. WPPSI = Wechsler Pre-School and Primary Scale of Intelligence (full-scale IQ).
Mentions: Genomic umbilical cord DNA from 24 SWS children was screened using the MBD array for differences in DNA methylation at birth associated with WPPSI IQ age 4 years (Figure 1). The subjects selected were representative of the range of WPPSI IQ measurements within the whole cohort. Statistical analysis of the data identified 41 DMROIs associated with IQ at age 4 years (Supplementary Table 4, available as Supplementary data at IJE online; Figure 2a).Figure 1.

Bottom Line: Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS 7-year-olds.Here, HES1 DMROI methylation predicted differences in early infant behaviour, known to be associated with academic success.Thus, our findings suggest that perinatal epigenetic processes mark later neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biological Sciences, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK, kal@soton.ac.uk.

No MeSH data available.


Related in: MedlinePlus