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Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.
Mattheisen, M; Samuels, J F; Wang, Y; 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; Qin, H-D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Liang, K-Y; Goes, F S; Maher, B; Pulver, A E; Shugart, Y Y; Valle, D; Lange, C; Nestadt, G.
Afiliação
  • Mattheisen M; 1] Department of Biomedicine and Center for Integrated Sequencing (iSEQ), Aarhus University, Aarhus, Denmark [2] Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA [3] Department of Genomic Mathematics, University of Bonn, Bonn, Germany.
  • 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.
  • 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 SciencesKeck 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.
  • Qin HD; Division of Intramural Research Program, National Institute of Mental Health, Unit of Statistical Genomics, Intramural Research Program, Bethesda, MD, 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; 1] Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA [2] Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
  • Liang KY; Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • 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.
  • Shugart YY; Division of Intramural Research Program, National Institute of Mental Health, Unit of Statistical Genomics, Intramural Research Program, Bethesda, MD, USA.
  • Valle D; Institute of Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lange C; 1] Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA [2] Department of Genomic Mathematics, University of Bonn, Bonn, Germany.
  • Nestadt G; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mol Psychiatry ; 20(3): 337-44, 2015 Mar.
Article em En | MEDLINE | ID: mdl-24821223
ABSTRACT
Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saúde da Família / Predisposição Genética para Doença / Transtorno Obsessivo-Compulsivo Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saúde da Família / Predisposição Genética para Doença / Transtorno Obsessivo-Compulsivo Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Alemanha