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Gene-environment interplay in externalizing behavior from childhood through adulthood / Tina KRETSCHMER in Journal of Child Psychology and Psychiatry, 63-10 (October 2022)
[article]
Titre : Gene-environment interplay in externalizing behavior from childhood through adulthood Type de document : Texte imprimé et/ou numérique Auteurs : Tina KRETSCHMER, Auteur ; Charlotte VRIJEN, Auteur ; Ilja Maria NOLTE, Auteur ; Jasmin WERTZ, Auteur ; Catharina A. HARTMAN, Auteur Année de publication : 2022 Article en page(s) : p.1206-1213 Langues : Anglais (eng) Mots-clés : Adolescent Adult Antisocial Personality Disorder/genetics Child Child Behavior Genetic Predisposition to Disease Humans Longitudinal Studies Multifactorial Inheritance Prospective Studies Externalising disorder family functioning gene-environment interaction (GxE) molecular genetics Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene-environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene-environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior. METHOD: Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline=2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self-reports. Genome-wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring. RESULTS: Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene-environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture. CONCLUSIONS: A very small evocative gene-environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems. En ligne : http://dx.doi.org/10.1111/jcpp.13652 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1206-1213[article] Gene-environment interplay in externalizing behavior from childhood through adulthood [Texte imprimé et/ou numérique] / Tina KRETSCHMER, Auteur ; Charlotte VRIJEN, Auteur ; Ilja Maria NOLTE, Auteur ; Jasmin WERTZ, Auteur ; Catharina A. HARTMAN, Auteur . - 2022 . - p.1206-1213.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1206-1213
Mots-clés : Adolescent Adult Antisocial Personality Disorder/genetics Child Child Behavior Genetic Predisposition to Disease Humans Longitudinal Studies Multifactorial Inheritance Prospective Studies Externalising disorder family functioning gene-environment interaction (GxE) molecular genetics Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene-environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene-environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior. METHOD: Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline=2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self-reports. Genome-wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring. RESULTS: Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene-environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture. CONCLUSIONS: A very small evocative gene-environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems. En ligne : http://dx.doi.org/10.1111/jcpp.13652 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice / R. T. MOLENHUIS in Molecular Autism, 9 (2018)
[article]
Titre : Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice Type de document : Texte imprimé et/ou numérique Auteurs : R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; M. J. V. BRANDT, Auteur ; P. E. VAN SOLDT, Auteur ; H. J. ABU-TOAMIH ATAMNI, Auteur ; J. P. H. BURBACH, Auteur ; F. A. IRAQI, Auteur ; R. F. MOTT, Auteur ; M. J. H. KAS, Auteur Article en page(s) : 63 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/*genetics Genetics, Behavioral/*methods/standards Genome-Wide Association Study/*methods/standards Male Mice Mice, Inbred C57BL Multifactorial Inheritance Quantitative Trait Loci Reference Standards *Animal models *Autism *Behavioral neuroscience *Genetic reference population *Histamine 3 receptor *Neurodevelopmental disorders *Quantitative genetics *Repetitive behavior Care and Use Committee of Tel Aviv University.Not applicable.The 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: Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation on a fixed genetic background. Recent human genetic studies however indicate that a clinical diagnosis with ASDAutism Spectrum Disorder (ASD) is almost always associated with multiple genetic fore- and background changes. The translational value of animal model studies would be greatly enhanced if genetic insults could be studied in a more quantitative framework across genetic backgrounds. Methods: We used the Collaborative Cross (CC), a novel mouse genetic reference population, to investigate the quantitative genetic architecture of mouse behavioral phenotypes commonly used in animal models for NDD. Results: Classical tests of social recognition and grooming phenotypes appeared insufficient for quantitative studies due to genetic dilution and limited heritability. In contrast, digging, locomotor activity, and stereotyped exploratory patterns were characterized by continuous distribution across our CC sample and also mapped to quantitative trait loci containing genes associated with corresponding phenotypes in human populations. Conclusions: These findings show that the CC can move animal model studies beyond comparative single gene-single background designs, and point out which type of behavioral phenotypes are most suitable to quantify the effect of developmental etiologies across multiple genetic backgrounds. En ligne : https://dx.doi.org/10.1186/s13229-018-0252-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389
in Molecular Autism > 9 (2018) . - 63 p.[article] Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice [Texte imprimé et/ou numérique] / R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; M. J. V. BRANDT, Auteur ; P. E. VAN SOLDT, Auteur ; H. J. ABU-TOAMIH ATAMNI, Auteur ; J. P. H. BURBACH, Auteur ; F. A. IRAQI, Auteur ; R. F. MOTT, Auteur ; M. J. H. KAS, Auteur . - 63 p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 63 p.
Mots-clés : Animals Autism Spectrum Disorder/*genetics Genetics, Behavioral/*methods/standards Genome-Wide Association Study/*methods/standards Male Mice Mice, Inbred C57BL Multifactorial Inheritance Quantitative Trait Loci Reference Standards *Animal models *Autism *Behavioral neuroscience *Genetic reference population *Histamine 3 receptor *Neurodevelopmental disorders *Quantitative genetics *Repetitive behavior Care and Use Committee of Tel Aviv University.Not applicable.The 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: Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation on a fixed genetic background. Recent human genetic studies however indicate that a clinical diagnosis with ASDAutism Spectrum Disorder (ASD) is almost always associated with multiple genetic fore- and background changes. The translational value of animal model studies would be greatly enhanced if genetic insults could be studied in a more quantitative framework across genetic backgrounds. Methods: We used the Collaborative Cross (CC), a novel mouse genetic reference population, to investigate the quantitative genetic architecture of mouse behavioral phenotypes commonly used in animal models for NDD. Results: Classical tests of social recognition and grooming phenotypes appeared insufficient for quantitative studies due to genetic dilution and limited heritability. In contrast, digging, locomotor activity, and stereotyped exploratory patterns were characterized by continuous distribution across our CC sample and also mapped to quantitative trait loci containing genes associated with corresponding phenotypes in human populations. Conclusions: These findings show that the CC can move animal model studies beyond comparative single gene-single background designs, and point out which type of behavioral phenotypes are most suitable to quantify the effect of developmental etiologies across multiple genetic backgrounds. En ligne : https://dx.doi.org/10.1186/s13229-018-0252-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 Polygenic risks for joint developmental trajectories of internalizing and externalizing problems: findings from the ALSPAC cohort / Lydia Gabriela SPEYER in Journal of Child Psychology and Psychiatry, 63-8 (August 2022)
[article]
Titre : Polygenic risks for joint developmental trajectories of internalizing and externalizing problems: findings from the ALSPAC cohort Type de document : Texte imprimé et/ou numérique Auteurs : Lydia Gabriela SPEYER, Auteur ; Samuel NEAVES, Auteur ; Hildigunnur Anna HALL, Auteur ; Gibran HEMANI, Auteur ; Michael Vincent LOMBARDO, Auteur ; Aja Louise MURRAY, Auteur ; Bonnie AUYEUNG, Auteur ; Michelle LUCIANO, Auteur Article en page(s) : p.948-956 Langues : Anglais (eng) Mots-clés : Adolescent Child Child, Preschool Female Humans Longitudinal Studies Male Mothers Multifactorial Inheritance Pregnancy Risk Factors Smoking Alspac Joint mental health trajectories externalizing internalizing polygenic risk Index. décimale : PER Périodiques Résumé : BACKGROUND: Joint developmental trajectories of internalizing and externalizing problems show considerable heterogeneity; however, this can be parsed into a small number of meaningful subgroups. Doing so offered insights into risk factors that lead to different patterns of internalizing/externalizing trajectories. However, despite both domains of problems showing strong heritability, no study has yet considered genetic risks as predictors of joint internalizing/externalizing problem trajectories. METHODS: Using parallel process latent class growth analysis, we estimated joint developmental trajectories of internalizing and externalizing difficulties assessed across ages 4 to 16 using the Strengths and Difficulties Questionnaire. Multinomial logistic regression was used to evaluate a range of demographic, perinatal, maternal mental health, and child and maternal polygenic predictors of group membership. Participants included 11,049 children taking part in the Avon Longitudinal Study of Parents and Children. Polygenic data were available for 7,127 children and 6,836 mothers. RESULTS: A 5-class model was judged optimal: Unaffected, Moderate Externalizing Symptoms, High Externalizing Symptoms, Moderate Internalizing and Externalizing Symptoms and High Internalizing and Externalizing Symptoms. Male sex, lower maternal age, maternal mental health problems, maternal smoking during pregnancy, higher child polygenic risk scores for ADHD and lower polygenic scores for IQ distinguished affected classes from the unaffected class. CONCLUSIONS: While affected classes could be relatively well separated from the unaffected class, phenotypic and polygenic predictors were limited in their ability to distinguish between different affected classes. Results thus add to existing evidence that internalizing and externalizing problems have mostly shared risk factors. En ligne : http://dx.doi.org/10.1111/jcpp.13549 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486
in Journal of Child Psychology and Psychiatry > 63-8 (August 2022) . - p.948-956[article] Polygenic risks for joint developmental trajectories of internalizing and externalizing problems: findings from the ALSPAC cohort [Texte imprimé et/ou numérique] / Lydia Gabriela SPEYER, Auteur ; Samuel NEAVES, Auteur ; Hildigunnur Anna HALL, Auteur ; Gibran HEMANI, Auteur ; Michael Vincent LOMBARDO, Auteur ; Aja Louise MURRAY, Auteur ; Bonnie AUYEUNG, Auteur ; Michelle LUCIANO, Auteur . - p.948-956.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 63-8 (August 2022) . - p.948-956
Mots-clés : Adolescent Child Child, Preschool Female Humans Longitudinal Studies Male Mothers Multifactorial Inheritance Pregnancy Risk Factors Smoking Alspac Joint mental health trajectories externalizing internalizing polygenic risk Index. décimale : PER Périodiques Résumé : BACKGROUND: Joint developmental trajectories of internalizing and externalizing problems show considerable heterogeneity; however, this can be parsed into a small number of meaningful subgroups. Doing so offered insights into risk factors that lead to different patterns of internalizing/externalizing trajectories. However, despite both domains of problems showing strong heritability, no study has yet considered genetic risks as predictors of joint internalizing/externalizing problem trajectories. METHODS: Using parallel process latent class growth analysis, we estimated joint developmental trajectories of internalizing and externalizing difficulties assessed across ages 4 to 16 using the Strengths and Difficulties Questionnaire. Multinomial logistic regression was used to evaluate a range of demographic, perinatal, maternal mental health, and child and maternal polygenic predictors of group membership. Participants included 11,049 children taking part in the Avon Longitudinal Study of Parents and Children. Polygenic data were available for 7,127 children and 6,836 mothers. RESULTS: A 5-class model was judged optimal: Unaffected, Moderate Externalizing Symptoms, High Externalizing Symptoms, Moderate Internalizing and Externalizing Symptoms and High Internalizing and Externalizing Symptoms. Male sex, lower maternal age, maternal mental health problems, maternal smoking during pregnancy, higher child polygenic risk scores for ADHD and lower polygenic scores for IQ distinguished affected classes from the unaffected class. CONCLUSIONS: While affected classes could be relatively well separated from the unaffected class, phenotypic and polygenic predictors were limited in their ability to distinguish between different affected classes. Results thus add to existing evidence that internalizing and externalizing problems have mostly shared risk factors. En ligne : http://dx.doi.org/10.1111/jcpp.13549 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene-environment correlation / Sandra MACHLITT-NORTHEN in Journal of Child Psychology and Psychiatry, 63-10 (October 2022)
[article]
Titre : Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene-environment correlation Type de document : Texte imprimé et/ou numérique Auteurs : Sandra MACHLITT-NORTHEN, Auteur ; Robert KEERS, Auteur ; Patricia B. MUNROE, Auteur ; David M. HOWARD, Auteur ; Vassily TRUBETSKOY, Auteur ; Michael PLUESS, Auteur Année de publication : 2022 Article en page(s) : p.1140-1152 Langues : Anglais (eng) Mots-clés : Cohort Studies Depression Depressive Disorder, Major/etiology/genetics Gene-Environment Interaction Genetic Predisposition to Disease Genome-Wide Association Study Humans Multifactorial Inheritance Risk Factors Schizophrenia/epidemiology/genetics Environment genetics major depressive disorder schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Whilst genetic and environmental risk factors for schizophrenia (SCZ) and major depressive disorder (MDD) have been established, it is unclear whether exposure to environmental risk factors is genetically confounded by passive, evocative or active gene-environment correlation (rGE). STUDY OBJECTIVE: This study aims to investigate: (a) whether the genetic risk for SCZ/MDD in children is correlated with established environmental and psychosocial risk factors in two British community samples, the 1958 National Child Development Study (NCDS) and the Millennium Cohort Study (MCS), (b) whether these associations vary between both psychopathologies, and (c) whether findings differ across the two cohorts which were born 42years apart. METHODS: Polygenic risk scores (PRS) from existing large genome-wide associations studies (GWAS) were applied to test the correlation between the child genetic risk for SCZ/MDD and known environmental risk factors. In addition, parental and child genetic data from MCS were used to distinguish between passive and evocative rGE. RESULTS: The child polygenic risk for SCZ and MDD was correlated with single parenthood in MCS. Moreover, the lack of father's involvement in child care was associated with the genetic risk for SCZ in NCDS. However, we also found associations between several indicators of low socioeconomic status and heightened genetic risk for MDD in children in both cohorts. Further, the genetic risk for MDD was associated with parental lack of interest in the child's education in NCDS as well as more maternal smoking and less maternal alcohol consumption during childhood in MCS. According to sensitivity analyses in MCS (controlling for parental genotype), more than half of our significant correlations reflected passive rGE. CONCLUSIONS: Findings suggest that several established environmental and psychosocial risk factors for SCZ and MDD are at least partially associated with children's genetic risk for these psychiatric disorders. En ligne : http://dx.doi.org/10.1111/jcpp.13657 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1140-1152[article] Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene-environment correlation [Texte imprimé et/ou numérique] / Sandra MACHLITT-NORTHEN, Auteur ; Robert KEERS, Auteur ; Patricia B. MUNROE, Auteur ; David M. HOWARD, Auteur ; Vassily TRUBETSKOY, Auteur ; Michael PLUESS, Auteur . - 2022 . - p.1140-1152.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1140-1152
Mots-clés : Cohort Studies Depression Depressive Disorder, Major/etiology/genetics Gene-Environment Interaction Genetic Predisposition to Disease Genome-Wide Association Study Humans Multifactorial Inheritance Risk Factors Schizophrenia/epidemiology/genetics Environment genetics major depressive disorder schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Whilst genetic and environmental risk factors for schizophrenia (SCZ) and major depressive disorder (MDD) have been established, it is unclear whether exposure to environmental risk factors is genetically confounded by passive, evocative or active gene-environment correlation (rGE). STUDY OBJECTIVE: This study aims to investigate: (a) whether the genetic risk for SCZ/MDD in children is correlated with established environmental and psychosocial risk factors in two British community samples, the 1958 National Child Development Study (NCDS) and the Millennium Cohort Study (MCS), (b) whether these associations vary between both psychopathologies, and (c) whether findings differ across the two cohorts which were born 42years apart. METHODS: Polygenic risk scores (PRS) from existing large genome-wide associations studies (GWAS) were applied to test the correlation between the child genetic risk for SCZ/MDD and known environmental risk factors. In addition, parental and child genetic data from MCS were used to distinguish between passive and evocative rGE. RESULTS: The child polygenic risk for SCZ and MDD was correlated with single parenthood in MCS. Moreover, the lack of father's involvement in child care was associated with the genetic risk for SCZ in NCDS. However, we also found associations between several indicators of low socioeconomic status and heightened genetic risk for MDD in children in both cohorts. Further, the genetic risk for MDD was associated with parental lack of interest in the child's education in NCDS as well as more maternal smoking and less maternal alcohol consumption during childhood in MCS. According to sensitivity analyses in MCS (controlling for parental genotype), more than half of our significant correlations reflected passive rGE. CONCLUSIONS: Findings suggest that several established environmental and psychosocial risk factors for SCZ and MDD are at least partially associated with children's genetic risk for these psychiatric disorders. En ligne : http://dx.doi.org/10.1111/jcpp.13657 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes / Jean-Baptiste PINGAULT in Journal of Child Psychology and Psychiatry, 63-10 (October 2022)
[article]
Titre : Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : Jean-Baptiste PINGAULT, Auteur ; Andrea G. ALLEGRINI, Auteur ; Tracy ODIGIE, Auteur ; Leonard FRACH, Auteur ; Jessie R. BALDWIN, Auteur ; Frühling V. RIJSDIJK, Auteur ; Frank DUDBRIDGE, Auteur Année de publication : 2022 Article en page(s) : p.1125-1139 Langues : Anglais (eng) Mots-clés : Cohort Studies Environmental Exposure/adverse effects Genetic Predisposition to Disease Genome-Wide Association Study Humans Midazolam Multifactorial Inheritance Phenotype Polygenic scores biases environment epidemiology phenotypes Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic influences are ubiquitous as virtually all phenotypes and most exposures typically classified as environmental have been found to be heritable. A polygenic score summarises the associations between millions of genetic variants and an outcome in a single value for each individual. Ever lowering costs have enabled the genotyping of many samples relevant to child psychology and psychiatry research, including cohort studies, leading to the proliferation of polygenic score studies. It is tempting to assume that associations detected between polygenic scores and phenotypes in those studies only reflect genetic effects. However, such associations can reflect many pathways (e.g. via environmental mediation) and biases. METHODS: Here, we provide a comprehensive overview of the many reasons why associations between polygenic scores, environmental exposures, and phenotypes exist. We include formal representations of common analyses in polygenic score studies using structural equation modelling. We derive biases, provide illustrative empirical examples and, when possible, mention steps that can be taken to alleviate those biases. RESULTS: Structural equation models and derivations show the many complexities arising from jointly modelling polygenic scores with environmental exposures and phenotypes. Counter-intuitive examples include that: (a) associations between polygenic scores and phenotypes may exist even in the absence of direct genetic effects; (b) associations between child polygenic scores and environmental exposures can exist in the absence of evocative/active gene-environment correlations; and (c) adjusting an exposure-outcome association for a polygenic score can increase rather than decrease bias. CONCLUSIONS: Strikingly, using polygenic scores may, in some cases, lead to more bias than not using them. Appropriately conducting and interpreting polygenic score studies thus requires researchers in child psychology and psychiatry and beyond to be versed in both epidemiological and genetic methods or build on interdisciplinary collaborations. En ligne : http://dx.doi.org/10.1111/jcpp.13607 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1125-1139[article] Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes [Texte imprimé et/ou numérique] / Jean-Baptiste PINGAULT, Auteur ; Andrea G. ALLEGRINI, Auteur ; Tracy ODIGIE, Auteur ; Leonard FRACH, Auteur ; Jessie R. BALDWIN, Auteur ; Frühling V. RIJSDIJK, Auteur ; Frank DUDBRIDGE, Auteur . - 2022 . - p.1125-1139.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1125-1139
Mots-clés : Cohort Studies Environmental Exposure/adverse effects Genetic Predisposition to Disease Genome-Wide Association Study Humans Midazolam Multifactorial Inheritance Phenotype Polygenic scores biases environment epidemiology phenotypes Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic influences are ubiquitous as virtually all phenotypes and most exposures typically classified as environmental have been found to be heritable. A polygenic score summarises the associations between millions of genetic variants and an outcome in a single value for each individual. Ever lowering costs have enabled the genotyping of many samples relevant to child psychology and psychiatry research, including cohort studies, leading to the proliferation of polygenic score studies. It is tempting to assume that associations detected between polygenic scores and phenotypes in those studies only reflect genetic effects. However, such associations can reflect many pathways (e.g. via environmental mediation) and biases. METHODS: Here, we provide a comprehensive overview of the many reasons why associations between polygenic scores, environmental exposures, and phenotypes exist. We include formal representations of common analyses in polygenic score studies using structural equation modelling. We derive biases, provide illustrative empirical examples and, when possible, mention steps that can be taken to alleviate those biases. RESULTS: Structural equation models and derivations show the many complexities arising from jointly modelling polygenic scores with environmental exposures and phenotypes. Counter-intuitive examples include that: (a) associations between polygenic scores and phenotypes may exist even in the absence of direct genetic effects; (b) associations between child polygenic scores and environmental exposures can exist in the absence of evocative/active gene-environment correlations; and (c) adjusting an exposure-outcome association for a polygenic score can increase rather than decrease bias. CONCLUSIONS: Strikingly, using polygenic scores may, in some cases, lead to more bias than not using them. Appropriately conducting and interpreting polygenic score studies thus requires researchers in child psychology and psychiatry and beyond to be versed in both epidemiological and genetic methods or build on interdisciplinary collaborations. En ligne : http://dx.doi.org/10.1111/jcpp.13607 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 Unique prediction of developmental psychopathology from genetic and familial risk / Robert J. LOUGHNAN in Journal of Child Psychology and Psychiatry, 63-12 (December 2022)
PermalinkUsing DNA to predict behaviour problems from preschool to adulthood / Agnieszka GIDZIELA in Journal of Child Psychology and Psychiatry, 63-7 (July 2022)
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