Commentary: What is the case for candidate gene approaches in the era of high-throughput genomics? A response to Border and Keller (2017) / Sarah R. MOORE in Journal of Child Psychology and Psychiatry, 58-3 (March 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-3 (March 2017) . - p.331-334 Titre : Commentary: What is the case for candidate gene approaches in the era of high-throughput genomics? A response to Border and Keller (2017) Type de document : Texte imprimé et/ou numérique Auteurs : Sarah R. MOORE, Auteur Article en page(s) : p.331-334 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Border and Keller argue that candidate gene approaches are outdated and out-of-touch with the current understanding of the genetic architecture of complex behavioral traits and should be abandoned in favor of unbiased, genome-wide approaches. Border and Keller further suggest that a candidate gene should not be selected for in-depth investigation unless identified by a well-powered genome-wide association study (GWAS). An alternative perspective is offered that candidate approaches can be sensible for developmental and deep-phenotyping studies aimed at elucidating particular biological pathways responsible for the emergence of psychological phenotypes, and that candidates should not necessarily be expected to be confirmed by, or solely selected based on, GWAS. Both candidate and whole genome strategies have limitations, and each approach is useful and valid in the quest to identify the elusive genetic architecture of complex behavioral phenotypes. En ligne : http://dx.doi.org/10.1111/jcpp.12697 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304 [article] Commentary: What is the case for candidate gene approaches in the era of high-throughput genomics? A response to Border and Keller (2017) [Texte imprimé et/ou numérique] / Sarah R. MOORE, Auteur . - p.331-334. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-3 (March 2017) . - p.331-334 Index. décimale : PER Périodiques Résumé : Border and Keller argue that candidate gene approaches are outdated and out-of-touch with the current understanding of the genetic architecture of complex behavioral traits and should be abandoned in favor of unbiased, genome-wide approaches. Border and Keller further suggest that a candidate gene should not be selected for in-depth investigation unless identified by a well-powered genome-wide association study (GWAS). An alternative perspective is offered that candidate approaches can be sensible for developmental and deep-phenotyping studies aimed at elucidating particular biological pathways responsible for the emergence of psychological phenotypes, and that candidates should not necessarily be expected to be confirmed by, or solely selected based on, GWAS. Both candidate and whole genome strategies have limitations, and each approach is useful and valid in the quest to identify the elusive genetic architecture of complex behavioral phenotypes. En ligne : http://dx.doi.org/10.1111/jcpp.12697 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304

Epigenetic correlates of neonatal contact in humans / Sarah R. MOORE in Development and Psychopathology, 29-5 (December 2017)  

Public ISBD [article]  inDevelopment and Psychopathology > 29-5 (December 2017) . - p.1517-1538 Titre : Epigenetic correlates of neonatal contact in humans Type de document : Texte imprimé et/ou numérique Auteurs : Sarah R. MOORE, Auteur ; Lisa M. MCEWEN, Auteur ; Jill QUIRT, Auteur ; Alex MORIN, Auteur ; Sarah M. MAH, Auteur ; Ronald G. BARR, Auteur ; W. Thomas BOYCE, Auteur ; Michael S. KOBOR, Auteur Article en page(s) : p.1517-1538 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), ?-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology. En ligne : http://dx.doi.org/10.1017/S0954579417001213 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=323 [article] Epigenetic correlates of neonatal contact in humans [Texte imprimé et/ou numérique] / Sarah R. MOORE, Auteur ; Lisa M. MCEWEN, Auteur ; Jill QUIRT, Auteur ; Alex MORIN, Auteur ; Sarah M. MAH, Auteur ; Ronald G. BARR, Auteur ; W. Thomas BOYCE, Auteur ; Michael S. KOBOR, Auteur . - p.1517-1538. Langues : Anglais (eng) in Development and Psychopathology > 29-5 (December 2017) . - p.1517-1538 Index. décimale : PER Périodiques Résumé : Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), ?-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology. En ligne : http://dx.doi.org/10.1017/S0954579417001213 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=323

What is the biological reality of gene–environment interaction estimates? An assessment of bias in developmental models / Sarah R. MOORE in Journal of Child Psychology and Psychiatry, 57-11 (November 2016)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 57-11 (November 2016) . - p.1258-1267 Titre : What is the biological reality of gene–environment interaction estimates? An assessment of bias in developmental models Type de document : Texte imprimé et/ou numérique Auteurs : Sarah R. MOORE, Auteur ; Felix THOEMMES, Auteur Article en page(s) : p.1258-1267 Langues : Anglais (eng) Mots-clés : Gene–environment interaction  methodology  child development  neural development  molecular genetics Index. décimale : PER Périodiques Résumé : Background Standard models used to test gene–environment interaction (G × E) hypotheses make the causal assumption that there are no unobserved variables that could be biasing the interaction estimate. Whether this assumption can be met in nonexperimental studies is unclear because the interactive biological pathways from genetic polymorphisms and environments to behavior, and the confounders that can be introduced along these pathways, are often not delineated. This is problematic in the context of studies focused on caregiver–child dyads, in which common genes and environments induce gene–environment correlation. To address the impact of sources of bias in G × E models specifically assessing the interaction between child genotype and caregiver behavior, we provide a causal framework that integrates biological and statistical concepts of G × E, and assess the magnitude of bias introduced by various confounding pathways in different causal circumstances. Methods A simulation assessed the magnitude of bias introduced by four types of confounding pathways in different causal models. Unadjusted and adjusted statistical models were then applied to the simulated data to assess the efficacy of these procedures to capture unbiased G × E estimates. Finally, the simulation was run under null effects of the genotype to assess the impact of biasing sources on the false-positive rate. Results Common environmental pathways between caregiver and child inflated G × E estimates and raised the false-positive rate. Evocative effects of the child also inflated G × E estimates. Conclusions Gene–environment interaction studies should be approached with consideration to the causal pathways at play and the confounding opportunities along these pathways to facilitate the inclusion of adequate statistical controls and correct inferences from study findings. Bridging biological and statistical concepts of G × E can significantly improve research design and the communication of how a G × E process fits into a broader developmental framework. En ligne : http://dx.doi.org/10.1111/jcpp.12579 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=295 [article] What is the biological reality of gene–environment interaction estimates? An assessment of bias in developmental models [Texte imprimé et/ou numérique] / Sarah R. MOORE, Auteur ; Felix THOEMMES, Auteur . - p.1258-1267. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 57-11 (November 2016) . - p.1258-1267 Mots-clés : Gene–environment interaction  methodology  child development  neural development  molecular genetics Index. décimale : PER Périodiques Résumé : Background Standard models used to test gene–environment interaction (G × E) hypotheses make the causal assumption that there are no unobserved variables that could be biasing the interaction estimate. Whether this assumption can be met in nonexperimental studies is unclear because the interactive biological pathways from genetic polymorphisms and environments to behavior, and the confounders that can be introduced along these pathways, are often not delineated. This is problematic in the context of studies focused on caregiver–child dyads, in which common genes and environments induce gene–environment correlation. To address the impact of sources of bias in G × E models specifically assessing the interaction between child genotype and caregiver behavior, we provide a causal framework that integrates biological and statistical concepts of G × E, and assess the magnitude of bias introduced by various confounding pathways in different causal circumstances. Methods A simulation assessed the magnitude of bias introduced by four types of confounding pathways in different causal models. Unadjusted and adjusted statistical models were then applied to the simulated data to assess the efficacy of these procedures to capture unbiased G × E estimates. Finally, the simulation was run under null effects of the genotype to assess the impact of biasing sources on the false-positive rate. Results Common environmental pathways between caregiver and child inflated G × E estimates and raised the false-positive rate. Evocative effects of the child also inflated G × E estimates. Conclusions Gene–environment interaction studies should be approached with consideration to the causal pathways at play and the confounding opportunities along these pathways to facilitate the inclusion of adequate statistical controls and correct inferences from study findings. Bridging biological and statistical concepts of G × E can significantly improve research design and the communication of how a G × E process fits into a broader developmental framework. En ligne : http://dx.doi.org/10.1111/jcpp.12579 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=295

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