Evaluating the interrelations between the autism polygenic score and psychiatric family history in risk for autism / Diana SCHENDEL in Autism Research, 15-1 (January 2022)  

Public ISBD [article]  inAutism Research > 15-1 (January 2022) . - p.171-182 Titre : Evaluating the interrelations between the autism polygenic score and psychiatric family history in risk for autism Type de document : Texte imprimé et/ou numérique Auteurs : Diana SCHENDEL, Auteur ; T. MUNK LAURSEN, Auteur ; C. ALBIÑANA, Auteur ; B. VILHJALMSSON, Auteur ; Christine LADD-ACOSTA, Auteur ; M. D. FALLIN, Auteur ; Kelly S. BENKE, Auteur ; B. LEE, Auteur ; J. GROVE, Auteur ; Amy E. KALKBRENNER, Auteur ; L. EJLSKOV, Auteur ; D. HOUGAARD, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; M. BAEKVAD-HANSEN, Auteur ; A. D. BØRGLUM, Auteur ; T. WERGE, Auteur ; M. NORDENTOFT, Auteur ; P. B. MORTENSEN, Auteur ; E. AGERBO, Auteur Article en page(s) : p.171-182 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/genetics  Autistic Disorder/genetics  Case-Control Studies  Humans  Multifactorial Inheritance/genetics  Risk Factors  Siblings  autism spectrum disorder  case-control studies  family history  genetic risk factors  polygenic risk score Index. décimale : PER Périodiques Résumé : Psychiatric family history or a high autism polygenic risk score (PRS) have been separately linked to autism spectrum disorder (ASD) risk. The study aimed to simultaneously consider psychiatric family history and individual autism genetic liability (PRS) in autism risk. We performed a case-control study of all Denmark singleton births, May 1981-December 2005, in Denmark at their first birthday and a known mother. Cases were diagnosed with ASD before 2013 and controls comprised a random sample of 30,000 births without ASD, excluding persons with non-Denmark-born parents, missing ASD PRS, non-European ancestry. Adjusted odds ratios (aOR) were estimated for ASD by PRS decile and by psychiatric history in parents or full siblings (8 mutually-exclusive categories) using logistic regression. Adjusted ASD PRS z-score least-squares means were estimated by psychiatric family history category. ASD risk (11,339 ASD cases; 20,175 controls) from ASD PRS was not substantially altered after accounting for psychiatric family history (e.g., ASD PRS 10th decile aOR: 2.35 (95% CI 2.11-2.63) before vs 2.11 (95% CI 1.91-2.40) after adjustment) nor from psychiatric family history after accounting for ASD PRS (e.g., ASD family history aOR: 6.73 (95% CI 5.89-7.68) before vs 6.32 (95% CI 5.53-7.22) after adjustment). ASD risk from ASD PRS varied slightly by psychiatric family history. While ASD risk from psychiatric family history was not accounted for by ASD PRS and vice versa, risk overlap between the two factors will likely increase as measures of genetic risk improve. The two factors are best viewed as complementary measures of family-based autism risk. LAY SUMMARY: Autism risk from a history of mental disorders in the immediate family was not explained by a measure of individual genetic risk (autism polygenic risk score) and vice versa. That is, genetic risk did not appear to overlap family history risk. As genetic measures for autism improve then the overlap in autism risk from family history versus genetic factors will likely increase, but further study may be needed to fully determine the components of risk and how they are inter-related between these key family factors. Meanwhile, the two factors may be best viewed as complementary measures of autism family-based risk. En ligne : http://dx.doi.org/10.1002/aur.2629 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Evaluating the interrelations between the autism polygenic score and psychiatric family history in risk for autism [Texte imprimé et/ou numérique] / Diana SCHENDEL, Auteur ; T. MUNK LAURSEN, Auteur ; C. ALBIÑANA, Auteur ; B. VILHJALMSSON, Auteur ; Christine LADD-ACOSTA, Auteur ; M. D. FALLIN, Auteur ; Kelly S. BENKE, Auteur ; B. LEE, Auteur ; J. GROVE, Auteur ; Amy E. KALKBRENNER, Auteur ; L. EJLSKOV, Auteur ; D. HOUGAARD, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; M. BAEKVAD-HANSEN, Auteur ; A. D. BØRGLUM, Auteur ; T. WERGE, Auteur ; M. NORDENTOFT, Auteur ; P. B. MORTENSEN, Auteur ; E. AGERBO, Auteur . - p.171-182. Langues : Anglais (eng) in Autism Research > 15-1 (January 2022) . - p.171-182 Mots-clés : Autism Spectrum Disorder/genetics  Autistic Disorder/genetics  Case-Control Studies  Humans  Multifactorial Inheritance/genetics  Risk Factors  Siblings  autism spectrum disorder  case-control studies  family history  genetic risk factors  polygenic risk score Index. décimale : PER Périodiques Résumé : Psychiatric family history or a high autism polygenic risk score (PRS) have been separately linked to autism spectrum disorder (ASD) risk. The study aimed to simultaneously consider psychiatric family history and individual autism genetic liability (PRS) in autism risk. We performed a case-control study of all Denmark singleton births, May 1981-December 2005, in Denmark at their first birthday and a known mother. Cases were diagnosed with ASD before 2013 and controls comprised a random sample of 30,000 births without ASD, excluding persons with non-Denmark-born parents, missing ASD PRS, non-European ancestry. Adjusted odds ratios (aOR) were estimated for ASD by PRS decile and by psychiatric history in parents or full siblings (8 mutually-exclusive categories) using logistic regression. Adjusted ASD PRS z-score least-squares means were estimated by psychiatric family history category. ASD risk (11,339 ASD cases; 20,175 controls) from ASD PRS was not substantially altered after accounting for psychiatric family history (e.g., ASD PRS 10th decile aOR: 2.35 (95% CI 2.11-2.63) before vs 2.11 (95% CI 1.91-2.40) after adjustment) nor from psychiatric family history after accounting for ASD PRS (e.g., ASD family history aOR: 6.73 (95% CI 5.89-7.68) before vs 6.32 (95% CI 5.53-7.22) after adjustment). ASD risk from ASD PRS varied slightly by psychiatric family history. While ASD risk from psychiatric family history was not accounted for by ASD PRS and vice versa, risk overlap between the two factors will likely increase as measures of genetic risk improve. The two factors are best viewed as complementary measures of family-based autism risk. LAY SUMMARY: Autism risk from a history of mental disorders in the immediate family was not explained by a measure of individual genetic risk (autism polygenic risk score) and vice versa. That is, genetic risk did not appear to overlap family history risk. As genetic measures for autism improve then the overlap in autism risk from family history versus genetic factors will likely increase, but further study may be needed to fully determine the components of risk and how they are inter-related between these key family factors. Meanwhile, the two factors may be best viewed as complementary measures of autism family-based risk. En ligne : http://dx.doi.org/10.1002/aur.2629 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

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

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