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Whole-genome association analysis of treatment response in obsessive-compulsive disorder.
Qin, H; Samuels, J F; Wang, Y; Zhu, Y; Grados, M A; Riddle, M A; Greenberg, B D; Knowles, J A; Fyer, A J; McCracken, J T; Murphy, D L; Rasmussen, S A; Cullen, B A; Piacentini, J; Geller, D; Stewart, S E; Pauls, D; Bienvenu, O J; Goes, F S; Maher, B; Pulver, A E; Valle, D; Lange, C; Mattheisen, M; McLaughlin, N C; Liang, K-Y; Nurmi, E L; Askland, K D; Nestadt, G; Shugart, Y Y.
Afiliação
  • Qin H; Unit on Statistical Genomics, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
  • Samuels JF; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Wang Y; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Zhu Y; Department of Epidemiology, Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA.
  • Grados MA; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Riddle MA; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Greenberg BD; Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Brown University, Providence, RI, USA.
  • Knowles JA; Department of Psychiatry, Keck Medical School, University of Southern California, Los Angeles, CA, USA.
  • Fyer AJ; College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • McCracken JT; Department of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, CA, USA.
  • Murphy DL; Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD, USA.
  • Rasmussen SA; Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Brown University, Providence, RI, USA.
  • Cullen BA; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Piacentini J; Department of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, CA, USA.
  • Geller D; Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Stewart SE; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
  • Pauls D; Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Brown University, Providence, RI, USA.
  • Bienvenu OJ; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Goes FS; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Maher B; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Pulver AE; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Valle D; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lange C; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mattheisen M; Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Institute of Human Genetics, Baltimore, MD, USA.
  • McLaughlin NC; Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
  • Liang KY; Department of Genomic Mathematics, University of Bonn, Bonn, Germany.
  • Nurmi EL; Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
  • Askland KD; Department of Genomic Mathematics, University of Bonn, Bonn, Germany.
  • Nestadt G; Department of Biomedicine and Center for Integrated Sequencing (iSEQ), Aarhus University, Aarhus, Denmark.
  • Shugart YY; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
Mol Psychiatry ; 21(2): 270-6, 2016 Feb.
Article em En | MEDLINE | ID: mdl-25824302
ABSTRACT
Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Obsessivo-Compulsivo Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Obsessivo-Compulsivo Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos