Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study / V. M. SINOPOLI in Journal of Child Psychology and Psychiatry, 60-12 (December 2019)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 60-12 (December 2019) . - p.1289-1299 Titre : Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study Type de document : Texte imprimé et/ou numérique Auteurs : V. M. SINOPOLI, Auteur ; L. ERDMAN, Auteur ; C. L. BURTON, Auteur ; L. S. PARK, Auteur ; A. DUPUIS, Auteur ; J. SHAN, Auteur ; T. GOODALE, Auteur ; S. M. SHAHEEN, Auteur ; J. CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; P. D. ARNOLD, Auteur Article en page(s) : p.1289-1299 Langues : Anglais (eng) Mots-clés : 5-httlpr  Htr1b  Htr2a  Obsessive-compulsive disorder  Slc6a4  genetic association  phenotypic heterogeneity  population-based  serotonin genes  serotonin system  symptom dimensions Index. décimale : PER Périodiques Résumé : BACKGROUND: Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. METHODS: Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. RESULTS: The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). CONCLUSIONS: This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group. En ligne : http://dx.doi.org/10.1111/jcpp.13079 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=412 [article] Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study [Texte imprimé et/ou numérique] / V. M. SINOPOLI, Auteur ; L. ERDMAN, Auteur ; C. L. BURTON, Auteur ; L. S. PARK, Auteur ; A. DUPUIS, Auteur ; J. SHAN, Auteur ; T. GOODALE, Auteur ; S. M. SHAHEEN, Auteur ; J. CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; P. D. ARNOLD, Auteur . - p.1289-1299. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 60-12 (December 2019) . - p.1289-1299 Mots-clés : 5-httlpr  Htr1b  Htr2a  Obsessive-compulsive disorder  Slc6a4  genetic association  phenotypic heterogeneity  population-based  serotonin genes  serotonin system  symptom dimensions Index. décimale : PER Périodiques Résumé : BACKGROUND: Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. METHODS: Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. RESULTS: The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). CONCLUSIONS: This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group. En ligne : http://dx.doi.org/10.1111/jcpp.13079 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=412

SWAN scale for ADHD trait-based genetic research: a validity and polygenic risk study / C. L. BURTON in Journal of Child Psychology and Psychiatry, 60-9 (September 2019)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 60-9 (September 2019) . - p.988-997 Titre : SWAN scale for ADHD trait-based genetic research: a validity and polygenic risk study Type de document : Texte imprimé et/ou numérique Auteurs : C. L. BURTON, Auteur ; L. WRIGHT, Auteur ; J. SHAN, Auteur ; B. XIAO, Auteur ; A. DUPUIS, Auteur ; T. GOODALE, Auteur ; S. M. SHAHEEN, Auteur ; E. C. CORFIELD, Auteur ; P. D. ARNOLD, Auteur ; Russell SCHACHAR, Auteur ; J. CROSBIE, Auteur Article en page(s) : p.988-997 Langues : Anglais (eng) Mots-clés : Adhd  Swan  polygenic risk score  psychometric validity  standardized norms Index. décimale : PER Périodiques Résumé : BACKGROUND: Population-based samples with valid, quantitative and genetically informative trait measures of psychopathology could be a powerful complement to case/control genetic designs. We report the convergent and predictive validity of the parent- and self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN). We tested if SWAN scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as traits and polygenic risk for disorders that co-occur with ADHD: anxiety and obsessive-compulsive disorder (OCD). METHODS: We collected parent- and self-report SWAN scores in a sample of 15,560 children and adolescents (6-17 years) recruited at a science museum (Spit for Science sample). We established age and sex norms for the SWAN. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with and without a reported ADHD diagnosis. These cut-points were validated in a clinic sample (266 ADHD cases; 36 controls). Convergent validity was established using the Conners' parent- and self-report scales. Using Spit for Science participants with genome-wide data (n = 5,154), we tested if low, medium and high SWAN scores were associated with polygenic risk for ADHD, OCD and anxiety disorders. RESULTS: Parent- and self-report SWAN scores showed high convergent validity with Conners' scales and distinguished ADHD participants with high sensitivity and specificity in the Spit for Science sample. In a clinic sample, the Spit for Science cut-points discriminated ADHD cases from controls with a sensitivity of 84% and specificity of 92%. High SWAN scores and scores above the Spit for Science cut-points were significantly associated with polygenic risk for ADHD. SWAN scores were not associated with polygenic risk for OCD or anxiety disorders. CONCLUSIONS: Our study supports the validity of the parent- and self-report SWAN scales and their potential in ADHD population-based genetic research. En ligne : http://dx.doi.org/10.1111/jcpp.13032 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405 [article] SWAN scale for ADHD trait-based genetic research: a validity and polygenic risk study [Texte imprimé et/ou numérique] / C. L. BURTON, Auteur ; L. WRIGHT, Auteur ; J. SHAN, Auteur ; B. XIAO, Auteur ; A. DUPUIS, Auteur ; T. GOODALE, Auteur ; S. M. SHAHEEN, Auteur ; E. C. CORFIELD, Auteur ; P. D. ARNOLD, Auteur ; Russell SCHACHAR, Auteur ; J. CROSBIE, Auteur . - p.988-997. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 60-9 (September 2019) . - p.988-997 Mots-clés : Adhd  Swan  polygenic risk score  psychometric validity  standardized norms Index. décimale : PER Périodiques Résumé : BACKGROUND: Population-based samples with valid, quantitative and genetically informative trait measures of psychopathology could be a powerful complement to case/control genetic designs. We report the convergent and predictive validity of the parent- and self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN). We tested if SWAN scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as traits and polygenic risk for disorders that co-occur with ADHD: anxiety and obsessive-compulsive disorder (OCD). METHODS: We collected parent- and self-report SWAN scores in a sample of 15,560 children and adolescents (6-17 years) recruited at a science museum (Spit for Science sample). We established age and sex norms for the SWAN. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with and without a reported ADHD diagnosis. These cut-points were validated in a clinic sample (266 ADHD cases; 36 controls). Convergent validity was established using the Conners' parent- and self-report scales. Using Spit for Science participants with genome-wide data (n = 5,154), we tested if low, medium and high SWAN scores were associated with polygenic risk for ADHD, OCD and anxiety disorders. RESULTS: Parent- and self-report SWAN scores showed high convergent validity with Conners' scales and distinguished ADHD participants with high sensitivity and specificity in the Spit for Science sample. In a clinic sample, the Spit for Science cut-points discriminated ADHD cases from controls with a sensitivity of 84% and specificity of 92%. High SWAN scores and scores above the Spit for Science cut-points were significantly associated with polygenic risk for ADHD. SWAN scores were not associated with polygenic risk for OCD or anxiety disorders. CONCLUSIONS: Our study supports the validity of the parent- and self-report SWAN scales and their potential in ADHD population-based genetic research. En ligne : http://dx.doi.org/10.1111/jcpp.13032 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405

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