Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS

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  • Manuel Mattheisen
  • J F Samuels, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • Y Wang, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • B D Greenberg, Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA., Denmark
  • A J Fyer, New York State Psychiatric Institute, College of Physicians and Surgeons at Columbia University, New York, NY, USA., Denmark
  • J T McCracken, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA., Denmark
  • D A Geller, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Denmark
  • D L Murphy, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA., Denmark
  • J A Knowles, Department of Psychiatry and Behavioral SciencesKeck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
  • ,
  • M A Grados, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • M A Riddle, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • S A Rasmussen, Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA., Denmark
  • N C McLaughlin, Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA., Denmark
  • E L Nurmi, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA., Denmark
  • K D Askland, Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA., Denmark
  • H-D Qin, Division of Intramural Research Program, National Institute of Mental Health, Unit of Statistical Genomics, Intramural Research Program, Bethesda, MD, USA., Denmark
  • B A Cullen, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • J Piacentini, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA., Denmark
  • D L Pauls, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Denmark
  • O J Bienvenu, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • S E Stewart, 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., Denmark
  • K-Y Liang, Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • ,
  • F S Goes, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Denmark
  • B Maher, Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • ,
  • A E Pulver, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • ,
  • Y Y Shugart, Division of Intramural Research Program, National Institute of Mental Health, Unit of Statistical Genomics, Intramural Research Program, Bethesda, MD, USA., Denmark
  • D Valle, Institute of Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • ,
  • C Lange, 1] Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA [2] Department of Genomic Mathematics, University of Bonn, Bonn, Germany., Denmark
  • G Nestadt, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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.Molecular Psychiatry advance online publication, 13 May 2014; doi:10.1038/mp.2014.43.

Original languageEnglish
JournalMolecular Psychiatry
ISSN1359-4184
DOIs
Publication statusPublished - 13 May 2014

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