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Case-control meta-analysis of blood DNA methylation and autism spectrum disorder / S. V. ANDREWS in Molecular Autism, 9 (2018)
[article]
Titre : Case-control meta-analysis of blood DNA methylation and autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : S. V. ANDREWS, Auteur ; B. SHEPPARD, Auteur ; G. C. WINDHAM, Auteur ; Laura A. SCHIEVE, Auteur ; Diana SCHENDEL, Auteur ; Lisa A. CROEN, Auteur ; P. CHOPRA, Auteur ; R. S. ALISCH, Auteur ; C. J. NEWSCHAFFER, Auteur ; S. T. WARREN, Auteur ; A. P. FEINBERG, Auteur ; M. D. FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur Article en page(s) : 40p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/blood/genetics Case-Control Studies Child, Preschool CpG Islands DNA Methylation Epigenesis, Genetic Female Genome-Wide Association Study Humans Male Autism spectrum disorders Epigenome Peripheral blood Simons Simplex Collection Study to Explore Early Development Index. décimale : PER Périodiques Résumé : Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 x 10(- 7). Seven CpGs showed differences at p < 1 x 10(- 5) and 48 at 1 x 10(- 4). Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0224-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 40p.[article] Case-control meta-analysis of blood DNA methylation and autism spectrum disorder [Texte imprimé et/ou numérique] / S. V. ANDREWS, Auteur ; B. SHEPPARD, Auteur ; G. C. WINDHAM, Auteur ; Laura A. SCHIEVE, Auteur ; Diana SCHENDEL, Auteur ; Lisa A. CROEN, Auteur ; P. CHOPRA, Auteur ; R. S. ALISCH, Auteur ; C. J. NEWSCHAFFER, Auteur ; S. T. WARREN, Auteur ; A. P. FEINBERG, Auteur ; M. D. FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur . - 40p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 40p.
Mots-clés : Autism Spectrum Disorder/blood/genetics Case-Control Studies Child, Preschool CpG Islands DNA Methylation Epigenesis, Genetic Female Genome-Wide Association Study Humans Male Autism spectrum disorders Epigenome Peripheral blood Simons Simplex Collection Study to Explore Early Development Index. décimale : PER Périodiques Résumé : Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 x 10(- 7). Seven CpGs showed differences at p < 1 x 10(- 5) and 48 at 1 x 10(- 4). Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0224-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Genome-wide DNA methylation patterns associated with sleep and mental health in children: a population-based study / Maria Elisabeth KOOPMAN-VERHOEFF in Journal of Child Psychology and Psychiatry, 61-10 (October 2020)
[article]
Titre : Genome-wide DNA methylation patterns associated with sleep and mental health in children: a population-based study Type de document : Texte imprimé et/ou numérique Auteurs : Maria Elisabeth KOOPMAN-VERHOEFF, Auteur ; Rosa H. MULDER, Auteur ; Jared M. SALETIN, Auteur ; Irwin REISS, Auteur ; Gijsbertus T. J. VAN DER HORST, Auteur ; Janine F. FELIX, Auteur ; Mary A. CARSKADON, Auteur ; Henning TIEMEIER, Auteur ; Charlotte A. M. CECIL, Auteur Article en page(s) : p.1061-1069 Langues : Anglais (eng) Mots-clés : DNA methylation accelerometer epigenetics epigenome psychopathology sleep Index. décimale : PER Périodiques Résumé : BACKGROUND: DNA methylation (DNAm) has been implicated in the biology of sleep. Yet, how DNAm patterns across the genome relate to different sleep outcomes, and whether these associations overlap with mental health is currently unknown. Here, we investigated associations of DNAm with sleep and mental health in a pediatric population. METHODS: This cross-sectional study included 465 10-year-old children (51.3% female) from the Generation R Study. Genome-wide DNAm levels were measured using the Illumina 450K array (peripheral blood). Sleep problems were assessed from self-report and mental health outcomes from maternal questionnaires. Wrist actigraphy was used in 188 11-year-old children to calculate sleep duration and midpoint sleep. Weighted gene co-expression network analysis was used to identify highly comethylated DNAm 'modules', which were tested for associations with sleep and mental health outcomes. RESULTS: We identified 64 DNAm modules, one of which associated with sleep duration after covariate and multiple testing adjustment. This module included CpG sites spanning 9 genes on chromosome 17, including MAPT - a key regulator of Tau proteins in the brain involved in neuronal function - as well as genes previously implicated in sleep duration. Follow-up analyses suggested that DNAm variation in this region is under considerable genetic control and shows strong blood-brain concordance. DNAm modules associated with sleep did not overlap with those associated with mental health. CONCLUSIONS: We identified one DNAm region associated with sleep duration, including genes previously reported by recent GWAS studies. Further research is warranted to examine the functional role of this region and its longitudinal association with sleep. En ligne : http://dx.doi.org/10.1111/jcpp.13252 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432
in Journal of Child Psychology and Psychiatry > 61-10 (October 2020) . - p.1061-1069[article] Genome-wide DNA methylation patterns associated with sleep and mental health in children: a population-based study [Texte imprimé et/ou numérique] / Maria Elisabeth KOOPMAN-VERHOEFF, Auteur ; Rosa H. MULDER, Auteur ; Jared M. SALETIN, Auteur ; Irwin REISS, Auteur ; Gijsbertus T. J. VAN DER HORST, Auteur ; Janine F. FELIX, Auteur ; Mary A. CARSKADON, Auteur ; Henning TIEMEIER, Auteur ; Charlotte A. M. CECIL, Auteur . - p.1061-1069.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 61-10 (October 2020) . - p.1061-1069
Mots-clés : DNA methylation accelerometer epigenetics epigenome psychopathology sleep Index. décimale : PER Périodiques Résumé : BACKGROUND: DNA methylation (DNAm) has been implicated in the biology of sleep. Yet, how DNAm patterns across the genome relate to different sleep outcomes, and whether these associations overlap with mental health is currently unknown. Here, we investigated associations of DNAm with sleep and mental health in a pediatric population. METHODS: This cross-sectional study included 465 10-year-old children (51.3% female) from the Generation R Study. Genome-wide DNAm levels were measured using the Illumina 450K array (peripheral blood). Sleep problems were assessed from self-report and mental health outcomes from maternal questionnaires. Wrist actigraphy was used in 188 11-year-old children to calculate sleep duration and midpoint sleep. Weighted gene co-expression network analysis was used to identify highly comethylated DNAm 'modules', which were tested for associations with sleep and mental health outcomes. RESULTS: We identified 64 DNAm modules, one of which associated with sleep duration after covariate and multiple testing adjustment. This module included CpG sites spanning 9 genes on chromosome 17, including MAPT - a key regulator of Tau proteins in the brain involved in neuronal function - as well as genes previously implicated in sleep duration. Follow-up analyses suggested that DNAm variation in this region is under considerable genetic control and shows strong blood-brain concordance. DNAm modules associated with sleep did not overlap with those associated with mental health. CONCLUSIONS: We identified one DNAm region associated with sleep duration, including genes previously reported by recent GWAS studies. Further research is warranted to examine the functional role of this region and its longitudinal association with sleep. En ligne : http://dx.doi.org/10.1111/jcpp.13252 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432