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Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD.
Guo, W; Samuels, J F; Wang, Y; Cao, H; Ritter, M; Nestadt, P S; Krasnow, J; Greenberg, B D; Fyer, A J; McCracken, J T; Geller, D A; Murphy, D L; Knowles, J A; Grados, M A; Riddle, M A; Rasmussen, S A; McLaughlin, N C; Nurmi, E L; Askland, K D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Goes, F S; Maher, B; Pulver, A E; Valle, D; Mattheisen, M; Qian, J; Nestadt, G; Shugart, Y Y.
Afiliação
  • Guo W; Unit on Statistical Genomics, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, USA.
  • Samuels JF; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wang Y; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Cao H; Elsevier Inc., Rockville, MD, USA.
  • Ritter M; Unit on Statistical Genomics, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, USA.
  • Nestadt PS; Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • Krasnow J; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Greenberg BD; Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA.
  • Fyer AJ; New York State Psychiatric Institute, College of Physicians and Surgeons at Columbia University, New York, NY, USA.
  • McCracken JT; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
  • Geller DA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Murphy DL; Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA.
  • Knowles JA; Department of Psychiatry and Behavioral Sciences Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
  • Grados MA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Riddle MA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rasmussen SA; Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA.
  • McLaughlin NC; Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA.
  • Nurmi EL; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
  • Askland KD; Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA.
  • Cullen BA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Piacentini J; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
  • Pauls DL; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Bienvenu OJ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Stewart SE; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
  • Goes FS; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Maher B; Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • Pulver AE; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Valle D; Institute of Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mattheisen M; Department of Biomedicine and Center for Integrated Sequencing (iSEQ), Aarhus University, Aarhus, Denmark; Harvard School of Public Health, Department of Biostatistics, Boston, MA, USA; Department of Genomic Mathematics, University of Bonn, Bonn, Germany.
  • Qian J; Life Science Institutes, Fudan University, Shanghai, China.
  • Nestadt G; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: gnestadt@jhmi.edu.
  • Shugart YY; Unit on Statistical Genomics, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, USA. Electronic address: yin.yao@nih.gov.
Eur Neuropsychopharmacol ; 27(7): 657-666, 2017 07.
Article em En | MEDLINE | ID: mdl-28641744
ABSTRACT
Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10-7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Característica Quantitativa Herdável / Herança Multifatorial / Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla / Transtorno do Espectro Autista / Transtorno Obsessivo-Compulsivo Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Característica Quantitativa Herdável / Herança Multifatorial / Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla / Transtorno do Espectro Autista / Transtorno Obsessivo-Compulsivo Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article