Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk / Ron NUDEL in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.369-381 Titre : Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk Type de document : Texte imprimé et/ou numérique Auteurs : Ron NUDEL, Auteur ; Camilla A. J. CHRISTIANI, Auteur ; Jessica OHLAND, Auteur ; Md Jamal UDDIN, Auteur ; Nicoline HEMAGER, Auteur ; Ditte ELLERSGAARD, Auteur ; Katrine S. SPANG, Auteur ; Birgitte K. BURTON, Auteur ; Aja N. GREVE, Auteur ; Ditte L. GANTRIIS, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne A. E. THORUP, Auteur ; Ole MORS, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur Article en page(s) : p.369-381 Langues : Anglais (eng) Mots-clés : attention deficit hyperactivity disorder  autism spectrum disorder  genome-wide association study  polygenic risk score  specific language impairment Index. décimale : PER Périodiques Résumé : Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R(2) = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R(2) = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R(2) = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders. En ligne : http://dx.doi.org/10.1002/aur.2211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk [Texte imprimé et/ou numérique] / Ron NUDEL, Auteur ; Camilla A. J. CHRISTIANI, Auteur ; Jessica OHLAND, Auteur ; Md Jamal UDDIN, Auteur ; Nicoline HEMAGER, Auteur ; Ditte ELLERSGAARD, Auteur ; Katrine S. SPANG, Auteur ; Birgitte K. BURTON, Auteur ; Aja N. GREVE, Auteur ; Ditte L. GANTRIIS, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne A. E. THORUP, Auteur ; Ole MORS, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur . - p.369-381. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.369-381 Mots-clés : attention deficit hyperactivity disorder  autism spectrum disorder  genome-wide association study  polygenic risk score  specific language impairment Index. décimale : PER Périodiques Résumé : Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R(2) = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R(2) = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R(2) = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders. En ligne : http://dx.doi.org/10.1002/aur.2211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Research Review: Do motor deficits during development represent an endophenotype for schizophrenia? A meta-analysis / Birgitte K. BURTON 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.446-456 Titre : Research Review: Do motor deficits during development represent an endophenotype for schizophrenia? A meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : Birgitte K. BURTON, Auteur ; Carsten HJORTHØJ, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne THORUP, Auteur ; Merete NORDENTOFT, Auteur ; Kerstin J. PLESSEN, Auteur Article en page(s) : p.446-456 Langues : Anglais (eng) Mots-clés : Motor function  endophenotype  early detection  first-degree relatives  schizophrenia Index. décimale : PER Périodiques Résumé : Background Early detection of schizophrenia risk is a critical goal in the field. Endophenotypes in children to relatives of affected individuals may contribute to this early detection. One of the lowest cost and longest theorized domains is motor development in children. Methods A meta-analysis was conducted comparing individuals ?21 years old with affected first-degree relatives (FDR) with (1) individuals from unaffected families (controls), or (2) individuals with FDR having other psychiatric disorders. Studies were classified by motor outcome and separate meta-analyses were performed across six correlated domains, with available N varying by domain. Results Inclusion criteria were met by k = 23 independent studies with a total N = 18,582, and N across domains varying from 167 to 8619. The youth from affected families had delays in gross and fine motor development in infancy (k = 3, n = 167, Hedges'g = 0.644, confidence intervals (CI) = [0.328, 0.960], p < .001), walking milestones (k = 3, n = 608, g = 0.444, CI = [0.108, 0.780], p = .01), coordination (k = 8, n = 8619, g = 0.625, CI = [0.453, 0.797], p < .0001), and had more abnormal movements such as involuntary movements (k = 6, n = 8365, g = 0.291, CI = [0.041, 0.542], p = .02) compared with controls. However, not all effects survived correction for publication bias. Effects for neurological soft signs were small and not reliably different from zero (k = 4, n = 548, g = 0.238, CI = [?0.106, 0.583], p = .18). When comparing the FDR group to youth from families with other psychiatric disorders, the FDR group was distinguished by poorer gross and fine motor skills (k = 2, n = 275, g = 0.847, CI = [0.393, 1.300], p < .001). Conclusions Motor deficits during development likely represent an endophenotype for schizophrenia, although its specificity is limited in relation to other serious mental disorders. It holds promise as a low cost domain for early risk detection, although it will have to be combined with other indicators to achieve clinically usable prediction accuracy. Impaired coordination was the most robust result with a moderate effect size and lack of heterogeneity and publication bias. En ligne : http://dx.doi.org/10.1111/jcpp.12479 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285 [article] Research Review: Do motor deficits during development represent an endophenotype for schizophrenia? A meta-analysis [Texte imprimé et/ou numérique] / Birgitte K. BURTON, Auteur ; Carsten HJORTHØJ, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne THORUP, Auteur ; Merete NORDENTOFT, Auteur ; Kerstin J. PLESSEN, Auteur . - p.446-456. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 57-4 (April 2016) . - p.446-456 Mots-clés : Motor function  endophenotype  early detection  first-degree relatives  schizophrenia Index. décimale : PER Périodiques Résumé : Background Early detection of schizophrenia risk is a critical goal in the field. Endophenotypes in children to relatives of affected individuals may contribute to this early detection. One of the lowest cost and longest theorized domains is motor development in children. Methods A meta-analysis was conducted comparing individuals ?21 years old with affected first-degree relatives (FDR) with (1) individuals from unaffected families (controls), or (2) individuals with FDR having other psychiatric disorders. Studies were classified by motor outcome and separate meta-analyses were performed across six correlated domains, with available N varying by domain. Results Inclusion criteria were met by k = 23 independent studies with a total N = 18,582, and N across domains varying from 167 to 8619. The youth from affected families had delays in gross and fine motor development in infancy (k = 3, n = 167, Hedges'g = 0.644, confidence intervals (CI) = [0.328, 0.960], p < .001), walking milestones (k = 3, n = 608, g = 0.444, CI = [0.108, 0.780], p = .01), coordination (k = 8, n = 8619, g = 0.625, CI = [0.453, 0.797], p < .0001), and had more abnormal movements such as involuntary movements (k = 6, n = 8365, g = 0.291, CI = [0.041, 0.542], p = .02) compared with controls. However, not all effects survived correction for publication bias. Effects for neurological soft signs were small and not reliably different from zero (k = 4, n = 548, g = 0.238, CI = [?0.106, 0.583], p = .18). When comparing the FDR group to youth from families with other psychiatric disorders, the FDR group was distinguished by poorer gross and fine motor skills (k = 2, n = 275, g = 0.847, CI = [0.393, 1.300], p < .001). Conclusions Motor deficits during development likely represent an endophenotype for schizophrenia, although its specificity is limited in relation to other serious mental disorders. It holds promise as a low cost domain for early risk detection, although it will have to be combined with other indicators to achieve clinically usable prediction accuracy. Impaired coordination was the most robust result with a moderate effect size and lack of heterogeneity and publication bias. En ligne : http://dx.doi.org/10.1111/jcpp.12479 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285

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