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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 Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis / P. ELLUL in Molecular Autism, 12 (2021)
[article]
Titre : Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : P. ELLUL, Auteur ; M. ROSENZWAJG, Auteur ; H. PEYRE, Auteur ; G. FOURCADE, Auteur ; E. MARIOTTI-FERRANDIZ, Auteur ; V. TREBOSSEN, Auteur ; D. KLATZMANN, Auteur ; R. DELORME, Auteur Article en page(s) : 68 p. Langues : Anglais (eng) Mots-clés : Asd Immunology Peripheral blood Regulatory T lymphocyte Th17 lymphocytes Index. décimale : PER Périodiques Résumé : BACKGROUND: Immune system dysfunction has been proposed to play a critical role in the pathophysiology of autism spectrum disorders (ASD). Conflicting reports of lymphocyte subpopulation abnormalities have been described in numerous studies of patients with ASD. To better define lymphocytes abnormalities in ASD, we performed a meta-analysis of the lymphocyte profiles from subjects with ASD. METHODS: We used the PRISMA recommendations to query PubMed, Embase, PsychoINFO, BIOSIS, Science Direct, Cochrane CENTRAL, and Clinicaltrials.gov for terms related to clinical diagnosis of ASD and to lymphocytes' populations. We selected studies exploring lymphocyte subpopulations in children with ASD. The search protocol has been registered in the international Prospective Register of Systematic Reviews (CRD42019121473). RESULTS: We selected 13 studies gathering 388 ASD patients and 326 healthy controls. A significant decrease in the CD4+?lymphocyte was found in ASD patients compared to controls [-?1.51 (95% CI?-?2.99;?-?0.04) p?=?0.04] (I(2)?=?96% [95% CI 94.6, 97.7], p?0.01). No significant difference was found for the CD8+?T, B and natural killer lymphocytes. Considering the CD4+?subpopulation, there was a significant decrease in regulatory T lymphocytes (Tregs) in ASD patients (n?=?114) compared to controls (n?=?107) [-?3.09 (95% CI?-?4.41;?-?1.76) p?=?0.0001]; (I(2)?=?90.9%, [95% CI 76.2, 96.5], p?0.0001) associated with an increase oin the Th17 lymphocytes (ASD; n?=?147 controls; n?=?128) [2.23 (95% CI 0.79; 3.66) p?=?0,002] (I(2)?=?95.1% [95% CI 90.4, 97.5], p?0.0001). LIMITATIONS: Several factors inducing heterogeneity should be considered. First, differences in the staining method may be responsible for a part in the heterogeneity of results. Second, ASD population is also by itself heterogeneous, underlying the need of studying sub-groups that are more homogeneous. CONCLUSION: Our meta-analysis indicates defects in CD4+?lymphocytes, specifically decrease oin Tregs and increase in Th17 in ASD patients and supports the development of targeted immunotherapies in the field of ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00472-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 68 p.[article] Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis [Texte imprimé et/ou numérique] / P. ELLUL, Auteur ; M. ROSENZWAJG, Auteur ; H. PEYRE, Auteur ; G. FOURCADE, Auteur ; E. MARIOTTI-FERRANDIZ, Auteur ; V. TREBOSSEN, Auteur ; D. KLATZMANN, Auteur ; R. DELORME, Auteur . - 68 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 68 p.
Mots-clés : Asd Immunology Peripheral blood Regulatory T lymphocyte Th17 lymphocytes Index. décimale : PER Périodiques Résumé : BACKGROUND: Immune system dysfunction has been proposed to play a critical role in the pathophysiology of autism spectrum disorders (ASD). Conflicting reports of lymphocyte subpopulation abnormalities have been described in numerous studies of patients with ASD. To better define lymphocytes abnormalities in ASD, we performed a meta-analysis of the lymphocyte profiles from subjects with ASD. METHODS: We used the PRISMA recommendations to query PubMed, Embase, PsychoINFO, BIOSIS, Science Direct, Cochrane CENTRAL, and Clinicaltrials.gov for terms related to clinical diagnosis of ASD and to lymphocytes' populations. We selected studies exploring lymphocyte subpopulations in children with ASD. The search protocol has been registered in the international Prospective Register of Systematic Reviews (CRD42019121473). RESULTS: We selected 13 studies gathering 388 ASD patients and 326 healthy controls. A significant decrease in the CD4+?lymphocyte was found in ASD patients compared to controls [-?1.51 (95% CI?-?2.99;?-?0.04) p?=?0.04] (I(2)?=?96% [95% CI 94.6, 97.7], p?0.01). No significant difference was found for the CD8+?T, B and natural killer lymphocytes. Considering the CD4+?subpopulation, there was a significant decrease in regulatory T lymphocytes (Tregs) in ASD patients (n?=?114) compared to controls (n?=?107) [-?3.09 (95% CI?-?4.41;?-?1.76) p?=?0.0001]; (I(2)?=?90.9%, [95% CI 76.2, 96.5], p?0.0001) associated with an increase oin the Th17 lymphocytes (ASD; n?=?147 controls; n?=?128) [2.23 (95% CI 0.79; 3.66) p?=?0,002] (I(2)?=?95.1% [95% CI 90.4, 97.5], p?0.0001). LIMITATIONS: Several factors inducing heterogeneity should be considered. First, differences in the staining method may be responsible for a part in the heterogeneity of results. Second, ASD population is also by itself heterogeneous, underlying the need of studying sub-groups that are more homogeneous. CONCLUSION: Our meta-analysis indicates defects in CD4+?lymphocytes, specifically decrease oin Tregs and increase in Th17 in ASD patients and supports the development of targeted immunotherapies in the field of ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00472-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459