54 recherche sur le mot-clé 'Case-Control Studies'

Risk factors for nonfatal self-harm and suicide among adolescents: two nested case-control studies conducted in the UK Clinical Practice Research Datalink / Lukasz CYBULSKI in Journal of Child Psychology and Psychiatry, 63-9 (September 2022)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 63-9 (September 2022) . - p.1078-1088 Titre : Risk factors for nonfatal self-harm and suicide among adolescents: two nested case-control studies conducted in the UK Clinical Practice Research Datalink Type de document : Texte imprimé et/ou numérique Auteurs : Lukasz CYBULSKI, Auteur ; Darren M. ASHCROFT, Auteur ; Matthew J. CARR, Auteur ; Shruti GARG, Auteur ; Carolyn A. CHEW-GRAHAM, Auteur ; Nav KAPUR, Auteur ; Roger T. WEBB, Auteur Article en page(s) : p.1078-1088 Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder  Case-Control Studies  Female  Humans  Male  Risk Factors  Self-Injurious Behavior/epidemiology/psychology  Suicide/prevention & control  United Kingdom/epidemiology  Adolescence  case-control  self-harm  suicide Index. décimale : PER Périodiques Résumé : BACKGROUND: The characteristics of adolescents who die by suicide have hitherto been examined in uncontrolled study designs, thereby precluding examination of risk factors. The degree to which antecedents of nonfatal self-harm and suicide at young age differ remains unknown. METHOD: We delineated two nested case-control studies of patients aged 10-19years using the Clinical Practice Research Datalink with interlinked hospital and national mortality records. Cases were adolescents who between 1st January 2003 and 31st December 2018 had died from suicide (N=324) - study 1; experienced their first self-harm episode (N=56,008) - study 2. In both studies, cases were matched on sex, age and practice-level deprivation quintile to 25 controls. By fitting conditional logistic regression, we examined how risks varied according to psychiatric diagnoses, prescribed psychotropic medication, patterns of clinical contact and area-level deprivation. RESULTS: Suicides occurred more often among boys (66%), but self-harm was more common in girls (68%). Most individuals who self-harmed or died from suicide presented to their GP at least once in the preceding year (85% and 75% respectively). Only a third of cases had one of the examined diagnostic categories recorded. Depression was most strongly associated with elevated risks for both outcomes (self-harm: OR 7.9; 95% CI 7.8-8.2; suicide: OR 7.4; 95% CI 5.5-9.9). Except for autism spectrum disorder, all other diagnostic categories were linked with similar risk elevations for self-harm as for suicide. Whilst self-harm risk rose incrementally with increasing levels of area-level deprivation, suicide risks did not. CONCLUSIONS: We observed few marked differences in risk factor profiles for nonfatal self-harm versus suicide. As most adolescents who had harmed themselves or died by suicide were known to services in the preceding year, their underlying pathology may not be adequately identified and treated. Our findings highlight the need for a multiagency approach to treatment and prevention. En ligne : http://dx.doi.org/10.1111/jcpp.13552 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 [article] Risk factors for nonfatal self-harm and suicide among adolescents: two nested case-control studies conducted in the UK Clinical Practice Research Datalink [Texte imprimé et/ou numérique] / Lukasz CYBULSKI, Auteur ; Darren M. ASHCROFT, Auteur ; Matthew J. CARR, Auteur ; Shruti GARG, Auteur ; Carolyn A. CHEW-GRAHAM, Auteur ; Nav KAPUR, Auteur ; Roger T. WEBB, Auteur . - p.1078-1088. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 63-9 (September 2022) . - p.1078-1088 Mots-clés : Adolescent  Autism Spectrum Disorder  Case-Control Studies  Female  Humans  Male  Risk Factors  Self-Injurious Behavior/epidemiology/psychology  Suicide/prevention & control  United Kingdom/epidemiology  Adolescence  case-control  self-harm  suicide Index. décimale : PER Périodiques Résumé : BACKGROUND: The characteristics of adolescents who die by suicide have hitherto been examined in uncontrolled study designs, thereby precluding examination of risk factors. The degree to which antecedents of nonfatal self-harm and suicide at young age differ remains unknown. METHOD: We delineated two nested case-control studies of patients aged 10-19years using the Clinical Practice Research Datalink with interlinked hospital and national mortality records. Cases were adolescents who between 1st January 2003 and 31st December 2018 had died from suicide (N=324) - study 1; experienced their first self-harm episode (N=56,008) - study 2. In both studies, cases were matched on sex, age and practice-level deprivation quintile to 25 controls. By fitting conditional logistic regression, we examined how risks varied according to psychiatric diagnoses, prescribed psychotropic medication, patterns of clinical contact and area-level deprivation. RESULTS: Suicides occurred more often among boys (66%), but self-harm was more common in girls (68%). Most individuals who self-harmed or died from suicide presented to their GP at least once in the preceding year (85% and 75% respectively). Only a third of cases had one of the examined diagnostic categories recorded. Depression was most strongly associated with elevated risks for both outcomes (self-harm: OR 7.9; 95% CI 7.8-8.2; suicide: OR 7.4; 95% CI 5.5-9.9). Except for autism spectrum disorder, all other diagnostic categories were linked with similar risk elevations for self-harm as for suicide. Whilst self-harm risk rose incrementally with increasing levels of area-level deprivation, suicide risks did not. CONCLUSIONS: We observed few marked differences in risk factor profiles for nonfatal self-harm versus suicide. As most adolescents who had harmed themselves or died by suicide were known to services in the preceding year, their underlying pathology may not be adequately identified and treated. Our findings highlight the need for a multiagency approach to treatment and prevention. En ligne : http://dx.doi.org/10.1111/jcpp.13552 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486

An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study / O. W. H. WONG in Autism Research, 14-10 (October 2021)  

Public ISBD [article]  inAutism Research > 14-10 (October 2021) . - p.2131-2142 Titre : An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study Type de document : Texte imprimé et/ou numérique Auteurs : O. W. H. WONG, Auteur ; A. M. W. LAM, Auteur ; Kelly Y. C. LAI, Auteur ; S. L. MA, Auteur ; S. F. HUNG, Auteur ; S. CHAN, Auteur ; S. WONG, Auteur ; P. W. L. LEUNG, Auteur Article en page(s) : p.2131-2142 Langues : Anglais (eng) Mots-clés : Anxiety/complications  Autism Spectrum Disorder/complications/epidemiology  Autistic Disorder/complications/epidemiology  Case-Control Studies  Child  Child, Preschool  Gastrointestinal Diseases/complications/epidemiology  Humans  Male  abdominal pain  anxiety  autism  constipation  functional gastrointestinal disorder  gut-brain axis  nausea Index. décimale : PER Périodiques Résumé : Children with autism commonly suffer from comorbid functional gastrointestinal disorders (FGID) and anxiety. The raised prevalence of both conditions in autism suggests complex reciprocal relationships, which are seldom explored in non-treatment-seeking FGID. The relationships between subtypes of FGID and anxiety are also unclear. This study recruited boys with autism and age-matched typically developing (TD) boys, aged 4-11?years, who were not actively seeking help for gastrointestinal problems. Their parents completed the Rome IV Diagnostic Questionnaires for Pediatric FGID. Four groups of children with and without autism/FGID were identified and compared on their anxiety level using the Spence children's anxiety scale. In 69 boys with autism and 69 age-matched TD boys, FGID were identified in 22 and 16 boys, respectively. ANCOVA demonstrated a significant interaction effect of autism and FGID on anxiety (F[1, 129] = 5.43, p = 0.021), while conditional logistic regression identified an interaction effect of autism and anxiety on the odds of FGID (OR 1.038, 95% CI 1.002-1.075, p = 0.038). Explorative post hoc analysis showed higher anxiety in functional nausea and vomiting disorder (p = 0.033) and functional abdominal pain disorder (p = 0.029) among boys with autism than TD boys with the same respective subtypes of FGID. In summary, among prepubertal boys with autism, the presence of FGID that are non-treatment-seeking in nature, has a significantly stronger association with higher levels of anxiety than TD boys. The strength of association may be more prominent in subtypes of FGID. Possible pathomechanisms including the underlying microbiota spectra and inflammatory paths should be explored in future studies. LAY SUMMARY: Anxiety and gastrointestinal problems are common symptoms in autism. Given that gut health could be linked to emotions, their association in young boys with autism was studied. The presence of nausea vomiting, or abdominal pain were associated with raised anxiety among boys with autism, yet this was not observed in typically developing boys. This suggests that anxiety among autistic children could be partly explained by the presence of FGID. En ligne : http://dx.doi.org/10.1002/aur.2555 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study [Texte imprimé et/ou numérique] / O. W. H. WONG, Auteur ; A. M. W. LAM, Auteur ; Kelly Y. C. LAI, Auteur ; S. L. MA, Auteur ; S. F. HUNG, Auteur ; S. CHAN, Auteur ; S. WONG, Auteur ; P. W. L. LEUNG, Auteur . - p.2131-2142. Langues : Anglais (eng) in Autism Research > 14-10 (October 2021) . - p.2131-2142 Mots-clés : Anxiety/complications  Autism Spectrum Disorder/complications/epidemiology  Autistic Disorder/complications/epidemiology  Case-Control Studies  Child  Child, Preschool  Gastrointestinal Diseases/complications/epidemiology  Humans  Male  abdominal pain  anxiety  autism  constipation  functional gastrointestinal disorder  gut-brain axis  nausea Index. décimale : PER Périodiques Résumé : Children with autism commonly suffer from comorbid functional gastrointestinal disorders (FGID) and anxiety. The raised prevalence of both conditions in autism suggests complex reciprocal relationships, which are seldom explored in non-treatment-seeking FGID. The relationships between subtypes of FGID and anxiety are also unclear. This study recruited boys with autism and age-matched typically developing (TD) boys, aged 4-11?years, who were not actively seeking help for gastrointestinal problems. Their parents completed the Rome IV Diagnostic Questionnaires for Pediatric FGID. Four groups of children with and without autism/FGID were identified and compared on their anxiety level using the Spence children's anxiety scale. In 69 boys with autism and 69 age-matched TD boys, FGID were identified in 22 and 16 boys, respectively. ANCOVA demonstrated a significant interaction effect of autism and FGID on anxiety (F[1, 129] = 5.43, p = 0.021), while conditional logistic regression identified an interaction effect of autism and anxiety on the odds of FGID (OR 1.038, 95% CI 1.002-1.075, p = 0.038). Explorative post hoc analysis showed higher anxiety in functional nausea and vomiting disorder (p = 0.033) and functional abdominal pain disorder (p = 0.029) among boys with autism than TD boys with the same respective subtypes of FGID. In summary, among prepubertal boys with autism, the presence of FGID that are non-treatment-seeking in nature, has a significantly stronger association with higher levels of anxiety than TD boys. The strength of association may be more prominent in subtypes of FGID. Possible pathomechanisms including the underlying microbiota spectra and inflammatory paths should be explored in future studies. LAY SUMMARY: Anxiety and gastrointestinal problems are common symptoms in autism. Given that gut health could be linked to emotions, their association in young boys with autism was studied. The presence of nausea vomiting, or abdominal pain were associated with raised anxiety among boys with autism, yet this was not observed in typically developing boys. This suggests that anxiety among autistic children could be partly explained by the presence of FGID. En ligne : http://dx.doi.org/10.1002/aur.2555 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study / M. LONG in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 1 p. Titre : Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study Type de document : Texte imprimé et/ou numérique Auteurs : M. LONG, Auteur ; M. GHISARI, Auteur ; L. KJELDSEN, Auteur ; M. WIELSOE, Auteur ; B. NORGAARD-PEDERSEN, Auteur ; E. L. MORTENSEN, Auteur ; Morsi W. ABDALLAH, Auteur ; E. C. BONEFELD-JORGENSEN, Auteur Article en page(s) : 1 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Amniotic Fluid/*chemistry  Animals  Autism Spectrum Disorder/epidemiology/*etiology  CHO Cells  Case-Control Studies  Child  Cricetinae  Cricetulus  Endocrine Disruptors/*analysis/toxicity  Female  Humans  Infant, Newborn  Male  Metals, Heavy/*analysis/toxicity  Middle Aged  *Amniotic fluid  *Autism  *Endocrine disrupting compounds  *Receptor activity  Newborn Screening Biobank and the Danish Data Protection Agency (Record No.  2009-41-3173) as well as the Central Denmark Region Ethics Committee on Health  Research (Record No. M-20090066). Since all data were obtained retrospectively in  an anonymized manner, there was no need to obtain consent from any of the  participants.Not applicableThe authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Evidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk. Methods: In this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance. Results: PFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p = 0.042; FDR q value = 0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR = 0.100; 95% CI 0.016, 0.630; p = 0.014; FDR q value = 0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR = 1.002; 95% CI 1.000, 1.004; p = 0.05). However, after multiple comparison correction, the association was not significant (FDR q value = 0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity. Conclusions: The presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0253-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study [Texte imprimé et/ou numérique] / M. LONG, Auteur ; M. GHISARI, Auteur ; L. KJELDSEN, Auteur ; M. WIELSOE, Auteur ; B. NORGAARD-PEDERSEN, Auteur ; E. L. MORTENSEN, Auteur ; Morsi W. ABDALLAH, Auteur ; E. C. BONEFELD-JORGENSEN, Auteur . - 1 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 1 p. Mots-clés : Adolescent  Adult  Amniotic Fluid/*chemistry  Animals  Autism Spectrum Disorder/epidemiology/*etiology  CHO Cells  Case-Control Studies  Child  Cricetinae  Cricetulus  Endocrine Disruptors/*analysis/toxicity  Female  Humans  Infant, Newborn  Male  Metals, Heavy/*analysis/toxicity  Middle Aged  *Amniotic fluid  *Autism  *Endocrine disrupting compounds  *Receptor activity  Newborn Screening Biobank and the Danish Data Protection Agency (Record No.  2009-41-3173) as well as the Central Denmark Region Ethics Committee on Health  Research (Record No. M-20090066). Since all data were obtained retrospectively in  an anonymized manner, there was no need to obtain consent from any of the  participants.Not applicableThe authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Evidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk. Methods: In this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance. Results: PFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p = 0.042; FDR q value = 0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR = 0.100; 95% CI 0.016, 0.630; p = 0.014; FDR q value = 0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR = 1.002; 95% CI 1.000, 1.004; p = 0.05). However, after multiple comparison correction, the association was not significant (FDR q value = 0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity. Conclusions: The presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0253-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Case-control meta-analysis of blood DNA methylation and autism spectrum disorder / S. V. ANDREWS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 40p. 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 [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

A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California / K. LYALL in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 24 p. Titre : A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California Type de document : Texte imprimé et/ou numérique Auteurs : K. LYALL, Auteur ; Jennifer L. AMES, Auteur ; M. PEARL, Auteur ; M. TRAGLIA, Auteur ; L. A. WEISS, Auteur ; G. C. WINDHAM, Auteur ; M. KHARRAZI, Auteur ; C. K. YOSHIDA, Auteur ; R. YOLKEN, Auteur ; Heather E. VOLK, Auteur ; Paul ASHWOOD, Auteur ; J. VAN DE WATER, Auteur ; Lisa A. CROEN, Auteur Article en page(s) : 24 p. Langues : Anglais (eng) Mots-clés : Adult  Autistic Disorder/blood/epidemiology/immunology  Biomarkers/blood  California/epidemiology  Case-Control Studies  Child  Cytokines/immunology  Endocrine Disruptors  Environmental Exposure  Environmental Pollutants  Female  Humans  Male  Pregnancy/immunology  Thyroid Hormones/blood  Vitamin D/blood  Young Adult  Autism  Early Markers for Autism  Immune response  Risk factors Index. décimale : PER Périodiques Résumé : BACKGROUND: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. METHODS: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n?=?629) and intellectual disability without ASD (ID, n?=?230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n?=?599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. RESULTS: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. LIMITATIONS: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. CONCLUSIONS: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures. En ligne : http://dx.doi.org/10.1186/s13229-021-00429-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California [Texte imprimé et/ou numérique] / K. LYALL, Auteur ; Jennifer L. AMES, Auteur ; M. PEARL, Auteur ; M. TRAGLIA, Auteur ; L. A. WEISS, Auteur ; G. C. WINDHAM, Auteur ; M. KHARRAZI, Auteur ; C. K. YOSHIDA, Auteur ; R. YOLKEN, Auteur ; Heather E. VOLK, Auteur ; Paul ASHWOOD, Auteur ; J. VAN DE WATER, Auteur ; Lisa A. CROEN, Auteur . - 24 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 24 p. Mots-clés : Adult  Autistic Disorder/blood/epidemiology/immunology  Biomarkers/blood  California/epidemiology  Case-Control Studies  Child  Cytokines/immunology  Endocrine Disruptors  Environmental Exposure  Environmental Pollutants  Female  Humans  Male  Pregnancy/immunology  Thyroid Hormones/blood  Vitamin D/blood  Young Adult  Autism  Early Markers for Autism  Immune response  Risk factors Index. décimale : PER Périodiques Résumé : BACKGROUND: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. METHODS: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n?=?629) and intellectual disability without ASD (ID, n?=?230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n?=?599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. RESULTS: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. LIMITATIONS: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. CONCLUSIONS: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures. En ligne : http://dx.doi.org/10.1186/s13229-021-00429-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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