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

被引：198

作者：

Mattheisen, M. ^{[1
,2
,3
,4
]}

Samuels, J. F. ^{[5
]}

Wang, Y. ^{[5
]}

Greenberg, B. D. ^{[6
]}

Fyer, A. J. ^{[7
]}

McCracken, J. T. ^{[8
]}

Geller, D. A. ^{[9
,10
]}

Murphy, D. L. ^{[11
]}

Knowles, J. A. ^{[12
]}

Grados, M. A. ^{[5
]}

Riddle, M. A. ^{[5
]}

Rasmussen, S. A. ^{[6
]}

McLaughlin, N. C. ^{[6
]}

Nurmi, E. L.

Askland, K. D. ^{[6
]}

Qin, H-D ^{[13
]}

Cullen, B. A. ^{[5
]}

Piacentini, J.

Pauls, D. L. ^{[9
,10
]}

Bienvenu, O. J. ^{[5
]}

Stewart, S. E. ^{[9
,10
,14
]}

Liang, K-Y ^{[15
]}

Goes, F. S. ^{[5
]}

Maher, B. ^{[15
]}

Pulver, A. E. ^{[5
]}

Shugart, Y. Y.

Valle, D. ^{[16
]}

Lange, C. ^{[3
,4
]}

Nestadt, G. ^{[5
]}

机构：

[1] Aarhus Univ, Dept Biomed, iPSYCH, Wilhjelm Meyers 4, DK-8000 Aarhus C, Denmark

[2] Aarhus Univ, Ctr Integrated Sequencing iSEQ, iPSYCH, DK-8000 Aarhus C, Denmark

[3] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[4] Univ Bonn, Dept Genom Math, Bonn, Germany

[5] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[6] Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA

[7] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA

[8] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA

[9] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA

[12] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA

[13] NIMH, Div Intramural Res Program, Unit Stat Genom, Intramural Res Program, Bethesda, MD 20892 USA

[14] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada

[15] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA

[16] Johns Hopkins Univ, Sch Med, Inst Human Genet, Baltimore, MD USA

来源：

MOLECULAR PSYCHIATRY | 2015年 / 20卷 / 03期

关键词：

FAMILY-BASED ASSOCIATION; TRANSPORTER GENE SLC1A1; TYROSINE PHOSPHATASES; PTP-SIGMA; VARIANTS; LINKAGE; LAR; BEHAVIORS; DELTA; LOCI;

D O I：

10.1038/mp.2014.43

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 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 x 10(-6), experiment-wide significant), as well as OFCC1 (P = 6.29 x 10(-5)). The suggestive findings in this study await replication in larger samples.

引用

页码：337 / 344

页数：8

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