Gene variants associated with antisocial behaviour: a latent variable approach / Mary Jane BENTLEY in Journal of Child Psychology and Psychiatry, 54-10 (October 2013)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 54-10 (October 2013) . - p.1074-1085 Titre : Gene variants associated with antisocial behaviour: a latent variable approach Type de document : texte imprimé Auteurs : Mary Jane BENTLEY, Auteur ; Haiqun LIN, Auteur ; Thomas V. FERNANDEZ, Auteur ; Maria LEE, Auteur ; Carolyn M. YRIGOLLEN, Auteur ; Andrew J. PAKSTIS, Auteur ; Liliya KATSOVICH, Auteur ; David L. OLDS, Auteur ; Elena L. GRIGORENKO, Auteur ; James F. LECKMAN, Auteur Article en page(s) : p.1074-1085 Langues : Anglais (eng) Mots-clés : Antisocial behaviour  latent variable analysis  shared variance  co-action of gene variants Index. décimale : PER Périodiques Résumé : Objective The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Results Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. Conclusions This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential ‘co-action’ of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a ‘shared’ variance across genetic risk alleles associated with complex neuropsychiatric dimensional phenotypes using relatively small numbers of well-characterized research participants. En ligne : http://dx.doi.org/10.1111/jcpp.12109 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=212 [article] Gene variants associated with antisocial behaviour: a latent variable approach [texte imprimé] / Mary Jane BENTLEY, Auteur ; Haiqun LIN, Auteur ; Thomas V. FERNANDEZ, Auteur ; Maria LEE, Auteur ; Carolyn M. YRIGOLLEN, Auteur ; Andrew J. PAKSTIS, Auteur ; Liliya KATSOVICH, Auteur ; David L. OLDS, Auteur ; Elena L. GRIGORENKO, Auteur ; James F. LECKMAN, Auteur . - p.1074-1085. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 54-10 (October 2013) . - p.1074-1085 Mots-clés : Antisocial behaviour  latent variable analysis  shared variance  co-action of gene variants Index. décimale : PER Périodiques Résumé : Objective The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Results Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. Conclusions This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential ‘co-action’ of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a ‘shared’ variance across genetic risk alleles associated with complex neuropsychiatric dimensional phenotypes using relatively small numbers of well-characterized research participants. En ligne : http://dx.doi.org/10.1111/jcpp.12109 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=212

Neurogenetic analysis of childhood disintegrative disorder / Abha R. GUPTA in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 19p. Titre : Neurogenetic analysis of childhood disintegrative disorder Type de document : texte imprimé Auteurs : Abha R. GUPTA, Auteur ; Alexander WESTPHAL, Auteur ; Daniel Y.J. YANG, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Jeffrey EILBOTT, Auteur ; Samir ZAIDI, Auteur ; Avery VOOS, Auteur ; Brent C. VANDER WYK, Auteur ; Pamela VENTOLA, Auteur ; Zainulabedin WAQAR, Auteur ; Thomas V. FERNANDEZ, Auteur ; Adife Gulhan ERCAN-SENCICEK, Auteur ; Michael F. WALKER, Auteur ; M. CHOI, Auteur ; Andrea SCHNEIDER, Auteur ; Tammy HEDDERLY, Auteur ; Gillian BAIRD, Auteur ; Hannah FRIEDMAN, Auteur ; Cara CORDEAUX, Auteur ; Alexandra RISTOW, Auteur ; Frederick SHIC, Auteur ; Fred R. VOLKMAR, Auteur ; Kevin A. PELPHREY, Auteur Article en page(s) : 19p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Childhood disintegrative disorder (CDD)  Eye tracking  Functional magnetic resonance imaging (fMRI)  Genetics  Intellectual disability (ID)  Regression Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences. METHODS: We pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces. RESULTS: We observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces. CONCLUSIONS: Given that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level. En ligne : http://dx.doi.org/10.1186/s13229-017-0133-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Neurogenetic analysis of childhood disintegrative disorder [texte imprimé] / Abha R. GUPTA, Auteur ; Alexander WESTPHAL, Auteur ; Daniel Y.J. YANG, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Jeffrey EILBOTT, Auteur ; Samir ZAIDI, Auteur ; Avery VOOS, Auteur ; Brent C. VANDER WYK, Auteur ; Pamela VENTOLA, Auteur ; Zainulabedin WAQAR, Auteur ; Thomas V. FERNANDEZ, Auteur ; Adife Gulhan ERCAN-SENCICEK, Auteur ; Michael F. WALKER, Auteur ; M. CHOI, Auteur ; Andrea SCHNEIDER, Auteur ; Tammy HEDDERLY, Auteur ; Gillian BAIRD, Auteur ; Hannah FRIEDMAN, Auteur ; Cara CORDEAUX, Auteur ; Alexandra RISTOW, Auteur ; Frederick SHIC, Auteur ; Fred R. VOLKMAR, Auteur ; Kevin A. PELPHREY, Auteur . - 19p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 19p. Mots-clés : Autism spectrum disorder (ASD)  Childhood disintegrative disorder (CDD)  Eye tracking  Functional magnetic resonance imaging (fMRI)  Genetics  Intellectual disability (ID)  Regression Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences. METHODS: We pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces. RESULTS: We observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces. CONCLUSIONS: Given that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level. En ligne : http://dx.doi.org/10.1186/s13229-017-0133-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Rare deleterious mutations of the gene EFR3A in autism spectrum disorders / Abha R. GUPTA in Molecular Autism, (April 2014)  

Public ISBD [article]  inMolecular Autism > (April 2014) . - p.1-14 Titre : Rare deleterious mutations of the gene EFR3A in autism spectrum disorders Type de document : texte imprimé Auteurs : Abha R. GUPTA, Auteur ; Michelle PIRRUCCELLO, Auteur ; Feng CHENG, Auteur ; Hyo Jung KANG, Auteur ; Thomas V. FERNANDEZ, Auteur ; Jeremy M. BASKIN, Auteur ; Murim CHOI, Auteur ; Li LIU, Auteur ; Adife Gulhan ERCAN-SENCICEK, Auteur ; John D. MURDOCH, Auteur ; Lambertus KLEI, Auteur ; Benjamin M. NEALE, Auteur ; Daniel FRANJIC, Auteur ; Mark J. DALY, Auteur ; Richard P. LIFTON, Auteur ; Pietro DE CAMILLI, Auteur ; Hongyu ZHAO, Auteur ; Nenad Å ESTAN, Auteur ; Matthew W. STATE, Auteur Article en page(s) : p.1-14 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-31 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] Rare deleterious mutations of the gene EFR3A in autism spectrum disorders [texte imprimé] / Abha R. GUPTA, Auteur ; Michelle PIRRUCCELLO, Auteur ; Feng CHENG, Auteur ; Hyo Jung KANG, Auteur ; Thomas V. FERNANDEZ, Auteur ; Jeremy M. BASKIN, Auteur ; Murim CHOI, Auteur ; Li LIU, Auteur ; Adife Gulhan ERCAN-SENCICEK, Auteur ; John D. MURDOCH, Auteur ; Lambertus KLEI, Auteur ; Benjamin M. NEALE, Auteur ; Daniel FRANJIC, Auteur ; Mark J. DALY, Auteur ; Richard P. LIFTON, Auteur ; Pietro DE CAMILLI, Auteur ; Hongyu ZHAO, Auteur ; Nenad Å ESTAN, Auteur ; Matthew W. STATE, Auteur . - p.1-14. Langues : Anglais (eng) in Molecular Autism > (April 2014) . - p.1-14 Index. décimale : PER Périodiques Résumé : Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-31 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

---

1 (1 - 3 / 3) Par page : 25 50 100 200