Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS
| Autor: | Abby J. Fyer, Jack Samuels, Benjamin D. Greenberg, David L. Pauls, Kung-Yee Liang, Ann E. Pulver, Kathleen D. Askland, Hai-De Qin, Yin Yao Shugart, Daniel A. Geller, Erika L. Nurmi, D. L. Murphy, Fernando S. Goes, Nicole C.R. McLaughlin, Mark A. Riddle, David Valle, S. A. Rasmussen, James T. McCracken, Yuchuan Wang, Brion S. Maher, Marco A. Grados, S. E. Stewart, Christoph Lange, Bernadette Cullen, John Piacentini, James A. Knowles, Manuel Mattheisen, Oscar J. Bienvenu, Gerald Nestadt |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Obsessive-Compulsive Disorder CDH10 Receptor-Like Protein Tyrosine Phosphatases Genome-wide association study protein tyrosine phosphatase delta Medical and Health Sciences 0302 clinical medicine Polymorphism (computer science) GRIA4 2.1 Biological and endogenous factors Cooperative Behavior Aetiology Oligonucleotide Array Sequence Analysis Genetics Psychiatry 0303 health sciences education.field_of_study biology Receptor-Like Protein Tyrosine Phosphatases Class 2 Single Nucleotide Biological Sciences 3. Good health Psychiatry and Mental health Mental Health Schizophrenia Female Psychology Chromosomes Human Pair 9 Clinical psychology Human Pair 9 Adult Genotype Population Polymorphism Single Nucleotide Article Chromosomes 03 medical and health sciences Cellular and Molecular Neuroscience Obsessive-Compulsive Young Adult GRIK2 Clinical Research medicine SNP Humans Genetic Predisposition to Disease Polymorphism education Molecular Biology 030304 developmental biology Family Health Gene Expression Profiling Human Genome Psychology and Cognitive Sciences CDH9 Class 2 medicine.disease schizophrenia Behavioral medicine biology.protein 030217 neurology & neurosurgery Follow-Up Studies Genome-Wide Association Study |
| Zdroj: | Molecular psychiatry, vol 20, iss 3 Molecular psychiatry 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 2014, ' Genome-wide association study in obsessive-compulsive disorder : results from the OCGAS ', Molecular Psychiatry . https://doi.org/10.1038/mp.2014.43 |
| DOI: | 10.1038/mp.2014.43 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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