Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder / H. PEYRE in Journal of Child Psychology and Psychiatry, 62-11 (November 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1285-1296 Titre : Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder Type de document : Texte imprimé et/ou numérique Auteurs : H. PEYRE, Auteur ; T. SCHOELER, Auteur ; C. LIU, Auteur ; C. M. WILLIAMS, Auteur ; N. HOERTEL, Auteur ; A. HAVDAHL, Auteur ; J. B. PINGAULT, Auteur Article en page(s) : p.1285-1296 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/epidemiology/genetics  Autism Spectrum Disorder/epidemiology/genetics  Comorbidity  Genome-Wide Association Study  Genomics  Humans  Paired Box Transcription Factors/genetics  Polymorphism, Single Nucleotide  Repressor Proteins/genetics  Autism spectrum disorder  Gwas  Snp  attention deficit hyperactivity disorder  colocalization  common genetic variants  comorbidity  genomic structural equation modelling Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two highly heritable neurodevelopmental disorders. Several lines of evidence point towards the presence of shared genetic factors underlying ASD and ADHD. We conducted genomic analyses of common risk variants (i.e. single nucleotide polymorphisms, SNPs) shared by ASD and ADHD, and those specific to each disorder. METHODS: With the summary data from two GWAS, one on ASD (N = 46,350) and another on ADHD (N = 55,374) individuals, we used genomic structural equation modelling and colocalization analysis to identify SNPs shared by ASD and ADHD and SNPs specific to each disorder. Functional genomic analyses were then conducted on shared and specific common genetic variants. Finally, we performed a bidirectional Mendelian randomization analysis to test whether the shared genetic risk between ASD and ADHD was interpretable in terms of reciprocal relationships between ASD and ADHD. RESULTS: We found that 37.5% of the SNPs associated with ASD (at p < 1e-6) colocalized with ADHD SNPs and that 19.6% of the SNPs associated with ADHD colocalized with ASD SNPs. We identified genes mapped to SNPs that are specific to ASD or ADHD and that are shared by ASD and ADHD, including two novel genes INSM1 and PAX1. Our bidirectional Mendelian randomization analyses indicated that the risk of ASD was associated with an increased risk of ADHD and vice versa. CONCLUSIONS: Using multivariate genomic analyses, the present study uncovers shared and specific genetic variants associated with ASD and ADHD. Further functional investigation of genes mapped to those shared variants may help identify pathophysiological pathways and new targets for treatment. En ligne : http://dx.doi.org/10.1111/jcpp.13479 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder [Texte imprimé et/ou numérique] / H. PEYRE, Auteur ; T. SCHOELER, Auteur ; C. LIU, Auteur ; C. M. WILLIAMS, Auteur ; N. HOERTEL, Auteur ; A. HAVDAHL, Auteur ; J. B. PINGAULT, Auteur . - p.1285-1296. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1285-1296 Mots-clés : Attention Deficit Disorder with Hyperactivity/epidemiology/genetics  Autism Spectrum Disorder/epidemiology/genetics  Comorbidity  Genome-Wide Association Study  Genomics  Humans  Paired Box Transcription Factors/genetics  Polymorphism, Single Nucleotide  Repressor Proteins/genetics  Autism spectrum disorder  Gwas  Snp  attention deficit hyperactivity disorder  colocalization  common genetic variants  comorbidity  genomic structural equation modelling Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two highly heritable neurodevelopmental disorders. Several lines of evidence point towards the presence of shared genetic factors underlying ASD and ADHD. We conducted genomic analyses of common risk variants (i.e. single nucleotide polymorphisms, SNPs) shared by ASD and ADHD, and those specific to each disorder. METHODS: With the summary data from two GWAS, one on ASD (N = 46,350) and another on ADHD (N = 55,374) individuals, we used genomic structural equation modelling and colocalization analysis to identify SNPs shared by ASD and ADHD and SNPs specific to each disorder. Functional genomic analyses were then conducted on shared and specific common genetic variants. Finally, we performed a bidirectional Mendelian randomization analysis to test whether the shared genetic risk between ASD and ADHD was interpretable in terms of reciprocal relationships between ASD and ADHD. RESULTS: We found that 37.5% of the SNPs associated with ASD (at p < 1e-6) colocalized with ADHD SNPs and that 19.6% of the SNPs associated with ADHD colocalized with ASD SNPs. We identified genes mapped to SNPs that are specific to ASD or ADHD and that are shared by ASD and ADHD, including two novel genes INSM1 and PAX1. Our bidirectional Mendelian randomization analyses indicated that the risk of ASD was associated with an increased risk of ADHD and vice versa. CONCLUSIONS: Using multivariate genomic analyses, the present study uncovers shared and specific genetic variants associated with ASD and ADHD. Further functional investigation of genes mapped to those shared variants may help identify pathophysiological pathways and new targets for treatment. En ligne : http://dx.doi.org/10.1111/jcpp.13479 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456

Heightened amygdala reactivity and increased stress generation predict internalizing symptoms in adults following childhood maltreatment / M. I. GERIN in Journal of Child Psychology and Psychiatry, 60-7 (July 2019)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 60-7 (July 2019) . - p.752-761 Titre : Heightened amygdala reactivity and increased stress generation predict internalizing symptoms in adults following childhood maltreatment Type de document : Texte imprimé et/ou numérique Auteurs : M. I. GERIN, Auteur ; E. VIDING, Auteur ; J. B. PINGAULT, Auteur ; V. B. PUETZ, Auteur ; A. R. KNODT, Auteur ; S. R. RADTKE, Auteur ; Bartholomew D. BRIGIDI, Auteur ; J. R. SWARTZ, Auteur ; A. R. HARIRI, Auteur ; E. J. MCCRORY, Auteur Article en page(s) : p.752-761 Langues : Anglais (eng) Mots-clés : Maltreatment  amygdala  child abuse  internalizing disorder  stress Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood maltreatment is one of the most potent predictors of future psychopathology, including internalizing disorders. It remains unclear whether heightened amygdala reactivity to threat and elevated stress exposure may be implicated in the pathogenesis and maintenance of internalizing disorders among individuals with a history of childhood maltreatment. METHODS: Using data from a sample of 1,144 young adults, we investigated the contribution of baseline threat-related amygdala reactivity and prospective major stressful life events to internalizing symptoms severity 1 year later (on average) in individuals with a history of maltreatment (n = 100) and propensity score matched nonmaltreated peers (n = 96). RESULTS: Even after stringently matching for several potentially confounding variables - including baseline internalizing symptoms, socioeconomic status and IQ - childhood maltreatment status predicted increased amygdala reactivity at baseline, elevated post-baseline exposure to major stressful life events and internalizing symptoms at follow-up. We also showed, for the first time, that amygdala reactivity at baseline and also post-baseline exposure to major stressful life events mediated the association between a history of maltreatment and future internalizing symptoms. CONCLUSIONS: These findings provide support for the view that maltreatment is a potent developmental insult leading to long-lasting neurocognitive recalibrations of the threat processing system. It is possible that such alterations, over time, may impact mental health functioning by compromising the ability to effectively negotiate everyday challenges (stress susceptibility). These alterations were not, however, found to sensitize an individual to the impact of major stressful life events. The results of this study also lend compelling support to the view that increased psychiatric risk, in the context of childhood maltreatment, follows from an increased propensity to experience major stressful life events (stress generation). En ligne : http://dx.doi.org/10.1111/jcpp.13041 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=401 [article] Heightened amygdala reactivity and increased stress generation predict internalizing symptoms in adults following childhood maltreatment [Texte imprimé et/ou numérique] / M. I. GERIN, Auteur ; E. VIDING, Auteur ; J. B. PINGAULT, Auteur ; V. B. PUETZ, Auteur ; A. R. KNODT, Auteur ; S. R. RADTKE, Auteur ; Bartholomew D. BRIGIDI, Auteur ; J. R. SWARTZ, Auteur ; A. R. HARIRI, Auteur ; E. J. MCCRORY, Auteur . - p.752-761. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 60-7 (July 2019) . - p.752-761 Mots-clés : Maltreatment  amygdala  child abuse  internalizing disorder  stress Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood maltreatment is one of the most potent predictors of future psychopathology, including internalizing disorders. It remains unclear whether heightened amygdala reactivity to threat and elevated stress exposure may be implicated in the pathogenesis and maintenance of internalizing disorders among individuals with a history of childhood maltreatment. METHODS: Using data from a sample of 1,144 young adults, we investigated the contribution of baseline threat-related amygdala reactivity and prospective major stressful life events to internalizing symptoms severity 1 year later (on average) in individuals with a history of maltreatment (n = 100) and propensity score matched nonmaltreated peers (n = 96). RESULTS: Even after stringently matching for several potentially confounding variables - including baseline internalizing symptoms, socioeconomic status and IQ - childhood maltreatment status predicted increased amygdala reactivity at baseline, elevated post-baseline exposure to major stressful life events and internalizing symptoms at follow-up. We also showed, for the first time, that amygdala reactivity at baseline and also post-baseline exposure to major stressful life events mediated the association between a history of maltreatment and future internalizing symptoms. CONCLUSIONS: These findings provide support for the view that maltreatment is a potent developmental insult leading to long-lasting neurocognitive recalibrations of the threat processing system. It is possible that such alterations, over time, may impact mental health functioning by compromising the ability to effectively negotiate everyday challenges (stress susceptibility). These alterations were not, however, found to sensitize an individual to the impact of major stressful life events. The results of this study also lend compelling support to the view that increased psychiatric risk, in the context of childhood maltreatment, follows from an increased propensity to experience major stressful life events (stress generation). En ligne : http://dx.doi.org/10.1111/jcpp.13041 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=401

The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence / Andrea G. ALLEGRINI in Journal of Child Psychology and Psychiatry, 61-1 (January 2020)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 61-1 (January 2020) . - p.30-39 Titre : The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence Type de document : Texte imprimé et/ou numérique Auteurs : Andrea G. ALLEGRINI, Auteur ; Rosa CHEESMAN, Auteur ; K. RIMFELD, Auteur ; S. SELZAM, Auteur ; J. B. PINGAULT, Auteur ; T. C. ELEY, Auteur ; R. PLOMIN, Auteur Article en page(s) : p.30-39 Langues : Anglais (eng) Mots-clés : Childhood psychopathology  behavioural genetics  genomics Index. décimale : PER Périodiques Résumé : BACKGROUND: Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self-, parent- and teacher-rated measures in childhood and adolescence. METHODS: The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p. RESULTS: Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%-60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%-78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%-0.9%). CONCLUSIONS: Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far-reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems. En ligne : http://dx.doi.org/10.1111/jcpp.13113 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=413 [article] The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence [Texte imprimé et/ou numérique] / Andrea G. ALLEGRINI, Auteur ; Rosa CHEESMAN, Auteur ; K. RIMFELD, Auteur ; S. SELZAM, Auteur ; J. B. PINGAULT, Auteur ; T. C. ELEY, Auteur ; R. PLOMIN, Auteur . - p.30-39. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 61-1 (January 2020) . - p.30-39 Mots-clés : Childhood psychopathology  behavioural genetics  genomics Index. décimale : PER Périodiques Résumé : BACKGROUND: Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self-, parent- and teacher-rated measures in childhood and adolescence. METHODS: The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p. RESULTS: Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%-60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%-78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%-0.9%). CONCLUSIONS: Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far-reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems. En ligne : http://dx.doi.org/10.1111/jcpp.13113 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=413

The role of birth weight on the causal pathway to child and adolescent ADHD symptomatology: a population-based twin differences longitudinal design / K. X. LIM in Journal of Child Psychology and Psychiatry, 59-10 (October 2018)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 59-10 (October 2018) . - p.1036-1043 Titre : The role of birth weight on the causal pathway to child and adolescent ADHD symptomatology: a population-based twin differences longitudinal design Type de document : Texte imprimé et/ou numérique Auteurs : K. X. LIM, Auteur ; C. Y. LIU, Auteur ; T. SCHOELER, Auteur ; Charlotte A. M. CECIL, Auteur ; Edward D. BARKER, Auteur ; E. VIDING, Auteur ; C. U. GREVEN, Auteur ; J. B. PINGAULT, Auteur Article en page(s) : p.1036-1043 Langues : Anglais (eng) Mots-clés : Attention-deficit/hyperactivity disorder birth weight hyperactivity/impulsivity inattention twin differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Available evidence points towards lower birth weight as a risk factor for the development of attention deficit/hyperactivity disorder (ADHD) symptoms. We probed the causal nature of this putative effect of birth weight on ADHD symptoms using the twin differences design, which accounts for genetic and shared environmental confounds. METHOD: In a large population-based twin sample - 3,499 monozygotic (MZ) and 6,698 dizygotic (DZ) pairs - parents, teachers or twins rated the twins' ADHD symptoms at nine assessment waves (2-16 years). We implemented the twin differences design, which completely accounts for shared environmental and genetic confounding in MZ twins. We tested whether: (a) the lighter-born twins had elevated ADHD symptoms compared to the heavier-born twins, by regressing within-pair differences of ADHD symptoms on within-pair differences of birth weight among MZ twins; (b) the effect of birth weight on ADHD was moderated by gender, gestational age and low birth weight; (c) this effect changed with age at ADHD assessment using adapted latent growth curve models; and (d) results differed for inattention and hyperactivity/impulsivity. RESULTS: Birth weight significantly predicted ADHD symptoms from early childhood to late adolescence. The lighter-born twin had more ADHD symptoms than the heavier-born cotwin among MZ twins across assessment waves and raters. No moderation effect was detected. The magnitude of the effect of birth weight decreased significantly across time for hyperactivity/impulsivity, but the decrease failed to reach significance for inattention. Estimates for inattention were significantly larger than for hyperactivity/impulsivity at each time point, implying stronger effect of birth weight on inattention symptoms. CONCLUSIONS: Our findings provide stringent evidence for environmental effect of lower birth weight on the causal pathway to elevated ADHD symptoms. Effect of birth weight persists across a 14-year period from childhood into late adolescence, in particular for inattention symptoms. En ligne : http://dx.doi.org/10.1111/jcpp.12949 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=369 [article] The role of birth weight on the causal pathway to child and adolescent ADHD symptomatology: a population-based twin differences longitudinal design [Texte imprimé et/ou numérique] / K. X. LIM, Auteur ; C. Y. LIU, Auteur ; T. SCHOELER, Auteur ; Charlotte A. M. CECIL, Auteur ; Edward D. BARKER, Auteur ; E. VIDING, Auteur ; C. U. GREVEN, Auteur ; J. B. PINGAULT, Auteur . - p.1036-1043. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 59-10 (October 2018) . - p.1036-1043 Mots-clés : Attention-deficit/hyperactivity disorder birth weight hyperactivity/impulsivity inattention twin differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Available evidence points towards lower birth weight as a risk factor for the development of attention deficit/hyperactivity disorder (ADHD) symptoms. We probed the causal nature of this putative effect of birth weight on ADHD symptoms using the twin differences design, which accounts for genetic and shared environmental confounds. METHOD: In a large population-based twin sample - 3,499 monozygotic (MZ) and 6,698 dizygotic (DZ) pairs - parents, teachers or twins rated the twins' ADHD symptoms at nine assessment waves (2-16 years). We implemented the twin differences design, which completely accounts for shared environmental and genetic confounding in MZ twins. We tested whether: (a) the lighter-born twins had elevated ADHD symptoms compared to the heavier-born twins, by regressing within-pair differences of ADHD symptoms on within-pair differences of birth weight among MZ twins; (b) the effect of birth weight on ADHD was moderated by gender, gestational age and low birth weight; (c) this effect changed with age at ADHD assessment using adapted latent growth curve models; and (d) results differed for inattention and hyperactivity/impulsivity. RESULTS: Birth weight significantly predicted ADHD symptoms from early childhood to late adolescence. The lighter-born twin had more ADHD symptoms than the heavier-born cotwin among MZ twins across assessment waves and raters. No moderation effect was detected. The magnitude of the effect of birth weight decreased significantly across time for hyperactivity/impulsivity, but the decrease failed to reach significance for inattention. Estimates for inattention were significantly larger than for hyperactivity/impulsivity at each time point, implying stronger effect of birth weight on inattention symptoms. CONCLUSIONS: Our findings provide stringent evidence for environmental effect of lower birth weight on the causal pathway to elevated ADHD symptoms. Effect of birth weight persists across a 14-year period from childhood into late adolescence, in particular for inattention symptoms. En ligne : http://dx.doi.org/10.1111/jcpp.12949 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=369

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