3 recherche sur le mot-clé 'Quantitative trait'

Heritability of quantitative autism spectrum traits in adults: A family-based study / Sara C. TAYLOR in Autism Research, 14-8 (August 2021)  

Public ISBD [article]  inAutism Research > 14-8 (August 2021) . - p.1543-1553 Titre : Heritability of quantitative autism spectrum traits in adults: A family-based study Type de document : texte imprimé Auteurs : Sara C. TAYLOR, Auteur ; Samantha STEEMAN, Auteur ; Brielle N. GEHRINGER, Auteur ; Holly C. DOW, Auteur ; Allison LANGER, Auteur ; Eric RAWOT, Auteur ; Leat PEREZ, Auteur ; Matthew GOODMAN, Auteur ; Zoe SMERNOFF, Auteur ; Mahip GREWAL, Auteur ; Oceania ESHRAGHI, Auteur ; Ashley A. PALLATHRA, Auteur ; Catherine OKSAS, Auteur ; Melissa MENDEZ, Auteur ; Ruben C. GUR, Auteur ; Daniel J. RADER, Auteur ; Maja BUÄŒAN, Auteur ; Laura ALMASY, Auteur ; Edward S. BRODKIN, Auteur Article en page(s) : p.1543-1553 Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/genetics  Autistic Disorder  Executive Function  Humans  Phenotype  Surveys and Questionnaires  adult  autism spectrum disorder  family studies  heritability  phenotype  quantitative trait Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) comprises a multi-dimensional set of quantitative behavioral traits expressed along a continuum in autistic and neurotypical individuals. ASD diagnosis-a dichotomous trait-is known to be highly heritable and has been used as the phenotype for most ASD genetic studies. But less is known about the heritability of autism spectrum quantitative traits, especially in adults, an important prerequisite for gene discovery. We sought to measure the heritability of many autism-relevant quantitative traits in adults high in autism spectrum traits and their extended family members. Among adults high in autism spectrum traits (n = 158) and their extended family members (n = 245), we calculated univariate and bivariate heritability estimates for 19 autism spectrum traits across several behavioral domains. We found nearly all tested autism spectrum quantitative traits to be significantly heritable (h(2)  = 0.24-0.79), including overall ASD traits, restricted repetitive behaviors, broader autism phenotype traits, social anxiety, and executive functioning. The degree of shared heritability varied based on method and specificity of the assessment measure. We found high shared heritability for the self-report measures and for most of the informant-report measures, with little shared heritability among performance-based cognition tasks. These findings suggest that many autism spectrum quantitative traits would be good, feasible candidates for future genetics studies, allowing for an increase in the power of autism gene discovery. Our findings suggest that the degree of shared heritability between traits depends on the assessment method (self-report vs. informant-report vs. performance-based tasks), as well as trait-specificity. LAY SUMMARY: We found that the scores from questionnaires and tasks measuring different types of behaviors and abilities related to autism spectrum disorder (ASD) were heritable (strongly influenced by gene variants passed down through a family) among autistic adults and their family members. These findings mean that these scores can be used in future studies interested in identifying specific genes and gene variants that are associated with different behaviors and abilities related with ASD. En ligne : http://dx.doi.org/10.1002/aur.2571 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Heritability of quantitative autism spectrum traits in adults: A family-based study [texte imprimé] / Sara C. TAYLOR, Auteur ; Samantha STEEMAN, Auteur ; Brielle N. GEHRINGER, Auteur ; Holly C. DOW, Auteur ; Allison LANGER, Auteur ; Eric RAWOT, Auteur ; Leat PEREZ, Auteur ; Matthew GOODMAN, Auteur ; Zoe SMERNOFF, Auteur ; Mahip GREWAL, Auteur ; Oceania ESHRAGHI, Auteur ; Ashley A. PALLATHRA, Auteur ; Catherine OKSAS, Auteur ; Melissa MENDEZ, Auteur ; Ruben C. GUR, Auteur ; Daniel J. RADER, Auteur ; Maja BUÄŒAN, Auteur ; Laura ALMASY, Auteur ; Edward S. BRODKIN, Auteur . - p.1543-1553. Langues : Anglais (eng) in Autism Research > 14-8 (August 2021) . - p.1543-1553 Mots-clés : Adult  Autism Spectrum Disorder/genetics  Autistic Disorder  Executive Function  Humans  Phenotype  Surveys and Questionnaires  adult  autism spectrum disorder  family studies  heritability  phenotype  quantitative trait Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) comprises a multi-dimensional set of quantitative behavioral traits expressed along a continuum in autistic and neurotypical individuals. ASD diagnosis-a dichotomous trait-is known to be highly heritable and has been used as the phenotype for most ASD genetic studies. But less is known about the heritability of autism spectrum quantitative traits, especially in adults, an important prerequisite for gene discovery. We sought to measure the heritability of many autism-relevant quantitative traits in adults high in autism spectrum traits and their extended family members. Among adults high in autism spectrum traits (n = 158) and their extended family members (n = 245), we calculated univariate and bivariate heritability estimates for 19 autism spectrum traits across several behavioral domains. We found nearly all tested autism spectrum quantitative traits to be significantly heritable (h(2)  = 0.24-0.79), including overall ASD traits, restricted repetitive behaviors, broader autism phenotype traits, social anxiety, and executive functioning. The degree of shared heritability varied based on method and specificity of the assessment measure. We found high shared heritability for the self-report measures and for most of the informant-report measures, with little shared heritability among performance-based cognition tasks. These findings suggest that many autism spectrum quantitative traits would be good, feasible candidates for future genetics studies, allowing for an increase in the power of autism gene discovery. Our findings suggest that the degree of shared heritability between traits depends on the assessment method (self-report vs. informant-report vs. performance-based tasks), as well as trait-specificity. LAY SUMMARY: We found that the scores from questionnaires and tasks measuring different types of behaviors and abilities related to autism spectrum disorder (ASD) were heritable (strongly influenced by gene variants passed down through a family) among autistic adults and their family members. These findings mean that these scores can be used in future studies interested in identifying specific genes and gene variants that are associated with different behaviors and abilities related with ASD. En ligne : http://dx.doi.org/10.1002/aur.2571 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits / Ellen M. HOWERTON in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits Type de document : texte imprimé Auteurs : Ellen M. HOWERTON, Auteur ; Valerie MORRILL, Auteur ; Rose SCHROTT, Auteur ; Jason DANIELS, Auteur ; Ashley Y. SONG, Auteur ; Kelly BENKE, Auteur ; Heather VOLK, Auteur ; Homayoon FARZADEGAN, Auteur ; Aimee ANIDO ALEXANDER, Auteur ; Amanda L. TAPIA, Auteur ; Gabriel S. DICHTER, Auteur ; Lisa A. CROEN, Auteur ; Lisa WIGGINS, Auteur ; Genevieve WOJCIK, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur Langues : Anglais (eng) Mots-clés : Humans  DNA Methylation/genetics  Male  Female  Case-Control Studies  Genome-Wide Association Study  Autism Spectrum Disorder/genetics  Child, Preschool  DNA-Binding Proteins/genetics  Transcription Factors/genetics  Epigenome  Quantitative Trait Loci  Repressor Proteins  Autism  DNA methylation  Quantitative trait  Social Responsiveness Scale  by the institutional review boards (IRBs) at each SEED site. SEED 1 recruitment  was approved by the IRB of each recruitment site: IRB-C, CDC Human Research  Protection Office  Kaiser Foundation Research Institute (KFRI) Kaiser Permanente  Northern California IRB, Colorado Multiple IRB, Emory University IRB, Georgia  Department of Public Health IRB, Maryland Department of Health and Mental Hygiene  IRB, Johns Hopkins Bloomberg School of Public Health IRB, University of North  Carolina IRB and Office of Human Research Ethics, IRB of The Children’s Hospital  of Philadelphia, and IRB of the University of Pennsylvania. All enrolled families  provided written consent for participation. Consent for publication: Not  applicable. Competing interests: CLA reports receiving consulting fees from the  University of Iowa for providing expertise on epigenetics outside of this work.  All other authors declare that they have no conflict of interest. The findings  and conclusions in this report are those of the authors and do not necessarily  represent the official position of the Centers for Disease Control and  Prevention. Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative measures of autism spectrum disorder (ASD)-related traits can provide insight into trait presentation across the population. Previous studies have identified epigenomic variation associated with ASD diagnosis, but few have evaluated quantitative traits. We sought to identify DNA methylation patterns in child blood associated with Social Responsiveness Scale score, Second Edition (SRS). METHODS: We conducted an epigenome-wide association study of SRS in child blood at approximately age 5 in the Study to Explore Early Development, a case-control study of ASD in the United States. We measured DNA methylation using the Illumina 450K array with 857 samples in our analysis after quality control. We performed regression of the M-value to identify single sites or differentially methylated regions (DMRs) associated with SRS scores, adjusting for sources of biological and technical variation. We examined methylation quantitative trait loci and conducted gene-ontology-term pathway analyses for regions of interest. RESULTS: We identified a region about 3.5 kb upstream of ZFP57 on chromosome 6 as differentially methylated (family-wise error rate [fwer] < 0.1) by continuous SRS T-score in the full sample (N = 857; fwer = 0.074) and among ASD cases only (N = 390; fwer = 0.021). ZFP57 encodes a transcription factor involved in imprinting regulation and maintenance, and this DMR has been previously associated with ASD in brain and buccal samples. CONCLUSIONS: Blood DNA methylation near ZFP57 was associated (fwer < 0.1) with SRS in the full population sample and appears to be largely driven by trait heterogeneity within the autism case group. Our results indicate DNA methylation associations with ASD quantitative traits are observable in a population and provide insights into specific biologic changes related to autism trait heterogeneity. En ligne : https://dx.doi.org/10.1186/s11689-025-09637-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits [texte imprimé] / Ellen M. HOWERTON, Auteur ; Valerie MORRILL, Auteur ; Rose SCHROTT, Auteur ; Jason DANIELS, Auteur ; Ashley Y. SONG, Auteur ; Kelly BENKE, Auteur ; Heather VOLK, Auteur ; Homayoon FARZADEGAN, Auteur ; Aimee ANIDO ALEXANDER, Auteur ; Amanda L. TAPIA, Auteur ; Gabriel S. DICHTER, Auteur ; Lisa A. CROEN, Auteur ; Lisa WIGGINS, Auteur ; Genevieve WOJCIK, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  DNA Methylation/genetics  Male  Female  Case-Control Studies  Genome-Wide Association Study  Autism Spectrum Disorder/genetics  Child, Preschool  DNA-Binding Proteins/genetics  Transcription Factors/genetics  Epigenome  Quantitative Trait Loci  Repressor Proteins  Autism  DNA methylation  Quantitative trait  Social Responsiveness Scale  by the institutional review boards (IRBs) at each SEED site. SEED 1 recruitment  was approved by the IRB of each recruitment site: IRB-C, CDC Human Research  Protection Office  Kaiser Foundation Research Institute (KFRI) Kaiser Permanente  Northern California IRB, Colorado Multiple IRB, Emory University IRB, Georgia  Department of Public Health IRB, Maryland Department of Health and Mental Hygiene  IRB, Johns Hopkins Bloomberg School of Public Health IRB, University of North  Carolina IRB and Office of Human Research Ethics, IRB of The Children’s Hospital  of Philadelphia, and IRB of the University of Pennsylvania. All enrolled families  provided written consent for participation. Consent for publication: Not  applicable. Competing interests: CLA reports receiving consulting fees from the  University of Iowa for providing expertise on epigenetics outside of this work.  All other authors declare that they have no conflict of interest. The findings  and conclusions in this report are those of the authors and do not necessarily  represent the official position of the Centers for Disease Control and  Prevention. Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative measures of autism spectrum disorder (ASD)-related traits can provide insight into trait presentation across the population. Previous studies have identified epigenomic variation associated with ASD diagnosis, but few have evaluated quantitative traits. We sought to identify DNA methylation patterns in child blood associated with Social Responsiveness Scale score, Second Edition (SRS). METHODS: We conducted an epigenome-wide association study of SRS in child blood at approximately age 5 in the Study to Explore Early Development, a case-control study of ASD in the United States. We measured DNA methylation using the Illumina 450K array with 857 samples in our analysis after quality control. We performed regression of the M-value to identify single sites or differentially methylated regions (DMRs) associated with SRS scores, adjusting for sources of biological and technical variation. We examined methylation quantitative trait loci and conducted gene-ontology-term pathway analyses for regions of interest. RESULTS: We identified a region about 3.5 kb upstream of ZFP57 on chromosome 6 as differentially methylated (family-wise error rate [fwer] < 0.1) by continuous SRS T-score in the full sample (N = 857; fwer = 0.074) and among ASD cases only (N = 390; fwer = 0.021). ZFP57 encodes a transcription factor involved in imprinting regulation and maintenance, and this DMR has been previously associated with ASD in brain and buccal samples. CONCLUSIONS: Blood DNA methylation near ZFP57 was associated (fwer < 0.1) with SRS in the full population sample and appears to be largely driven by trait heterogeneity within the autism case group. Our results indicate DNA methylation associations with ASD quantitative traits are observable in a population and provide insights into specific biologic changes related to autism trait heterogeneity. En ligne : https://dx.doi.org/10.1186/s11689-025-09637-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

The opposite end of the attention deficit hyperactivity disorder continuum: genetic and environmental aetiologies of extremely low ADHD traits / Corina U. GREVEN in Journal of Child Psychology and Psychiatry, 57-4 (April 2016)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 57-4 (April 2016) . - p.523-531 Titre : The opposite end of the attention deficit hyperactivity disorder continuum: genetic and environmental aetiologies of extremely low ADHD traits Type de document : texte imprimé Auteurs : Corina U. GREVEN, Auteur ; Andrew MERWOOD, Auteur ; Jolanda M.J. VAN DER MEER, Auteur ; Claire Margaret Alison HAWORTH, Auteur ; Nanda N. ROMMELSE, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : p.523-531 Langues : Anglais (eng) Mots-clés : Attention deficit hyperactivity disorder  quantitative trait  twin  extremes  positive genetics Index. décimale : PER Périodiques Résumé : Background Although attention deficit hyperactivity disorder (ADHD) is thought to reflect a continuously distributed quantitative trait, it is assessed through binary diagnosis or skewed measures biased towards its high, symptomatic extreme. A growing trend is to study the positive tail of normally distributed traits, a promising avenue, for example, to study high intelligence to increase power for gene-hunting for intelligence. However, the emergence of such a ‘positive genetics’ model has been tempered for ADHD due to poor phenotypic resolution at the low extreme. Overcoming this methodological limitation, we conduct the first study to assess the aetiologies of low extreme ADHD traits. Methods In a population-representative sample of 2,143 twins, the Strength and Weaknesses of ADHD Symptoms and Normal behaviour (SWAN) questionnaire was used to assess ADHD traits on a continuum from low to high. Aetiological influences on extreme ADHD traits were estimated using DeFries–Fulker extremes analysis. ADHD traits were related to behavioural, cognitive and home environmental outcomes using regression. Results Low extreme ADHD traits were significantly influenced by shared environmental factors (23–35%) but were not significantly heritable. In contrast, high-extreme ADHD traits showed significant heritability (39–51%) but no shared environmental influences. Compared to individuals with high extreme or with average levels of ADHD traits, individuals with low extreme ADHD traits showed fewer internalizing and externalizing behaviour problems, better cognitive performance and more positive behaviours and positive home environmental outcomes. Conclusions Shared environmental influences on low extreme ADHD traits may reflect passive gene-environment correlation, which arises because parents provide environments as well as passing on genes. Studying the low extreme opens new avenues to study mechanisms underlying previously neglected positive behaviours. This is different from the current deficit-based model of intervention, but congruent with a population-level approach to improving youth wellbeing. En ligne : http://dx.doi.org/10.1111/jcpp.12475 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285 [article] The opposite end of the attention deficit hyperactivity disorder continuum: genetic and environmental aetiologies of extremely low ADHD traits [texte imprimé] / Corina U. GREVEN, Auteur ; Andrew MERWOOD, Auteur ; Jolanda M.J. VAN DER MEER, Auteur ; Claire Margaret Alison HAWORTH, Auteur ; Nanda N. ROMMELSE, Auteur ; Jan K. BUITELAAR, Auteur . - p.523-531. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 57-4 (April 2016) . - p.523-531 Mots-clés : Attention deficit hyperactivity disorder  quantitative trait  twin  extremes  positive genetics Index. décimale : PER Périodiques Résumé : Background Although attention deficit hyperactivity disorder (ADHD) is thought to reflect a continuously distributed quantitative trait, it is assessed through binary diagnosis or skewed measures biased towards its high, symptomatic extreme. A growing trend is to study the positive tail of normally distributed traits, a promising avenue, for example, to study high intelligence to increase power for gene-hunting for intelligence. However, the emergence of such a ‘positive genetics’ model has been tempered for ADHD due to poor phenotypic resolution at the low extreme. Overcoming this methodological limitation, we conduct the first study to assess the aetiologies of low extreme ADHD traits. Methods In a population-representative sample of 2,143 twins, the Strength and Weaknesses of ADHD Symptoms and Normal behaviour (SWAN) questionnaire was used to assess ADHD traits on a continuum from low to high. Aetiological influences on extreme ADHD traits were estimated using DeFries–Fulker extremes analysis. ADHD traits were related to behavioural, cognitive and home environmental outcomes using regression. Results Low extreme ADHD traits were significantly influenced by shared environmental factors (23–35%) but were not significantly heritable. In contrast, high-extreme ADHD traits showed significant heritability (39–51%) but no shared environmental influences. Compared to individuals with high extreme or with average levels of ADHD traits, individuals with low extreme ADHD traits showed fewer internalizing and externalizing behaviour problems, better cognitive performance and more positive behaviours and positive home environmental outcomes. Conclusions Shared environmental influences on low extreme ADHD traits may reflect passive gene-environment correlation, which arises because parents provide environments as well as passing on genes. Studying the low extreme opens new avenues to study mechanisms underlying previously neglected positive behaviours. This is different from the current deficit-based model of intervention, but congruent with a population-level approach to improving youth wellbeing. En ligne : http://dx.doi.org/10.1111/jcpp.12475 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285