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

M. Mattheisen; J. F. Samuels; Y. Wang; B. D. Greenberg; A. J. Fyer; J. T. Mccracken; D. A. Geller; D. L. Murphy; J. A. Knowles; M. A. Grados; M. A. Riddle; S. A. Rasmussen; N. C. Mclaughlin; E. L. Nurmi; K. D. Askland; H. D. Qin; B. A. Cullen; J. Piacentini; D. L. Pauls; O. J. Bienvenu; S. E. Stewart; K. Y. Liang; F. S. Goes; B. Maher; A. E. Pulver; Y. Y. Shugart; D. Valle; C. Lange; G. Nestadt

doi:10.1038/mp.2014.43

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

M. Mattheisen, J. F. Samuels, Y. Wang, B. D. Greenberg, A. J. Fyer, J. T. Mccracken, D. A. Geller, D. L. Murphy, J. A. Knowles, M. A. Grados, M. A. Riddle, S. A. Rasmussen, N. C. Mclaughlin, E. L. Nurmi, K. D. Askland, H. D. Qin, B. A. Cullen, J. Piacentini, D. L. Pauls, O. J. BienvenuS. E. Stewart, K. Y. Liang, F. S. Goes, B. Maher, A. E. Pulver, Y. Y. Shugart, D. Valle, C. Lange, G. Nestadt

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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.

Original language	English (US)
Pages (from-to)	337-344
Number of pages	8
Journal	Molecular psychiatry
Volume	20
Issue number	3
DOIs	https://doi.org/10.1038/mp.2014.43
State	Published - Mar 12 2015

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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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., ... Nestadt, G. (2015). Genome-wide association study in obsessive-compulsive disorder: Results from the OCGAS. Molecular psychiatry, 20(3), 337-344. https://doi.org/10.1038/mp.2014.43

Mattheisen, M, Samuels, JF, Wang, Y, Greenberg, BD, Fyer, AJ, Mccracken, JT, Geller, DA, Murphy, DL, Knowles, JA, Grados, MA, Riddle, MA, Rasmussen, SA, Mclaughlin, NC, Nurmi, EL, Askland, KD, Qin, HD, Cullen, BA, Piacentini, J, Pauls, DL, Bienvenu, OJ, Stewart, SE, Liang, KY, Goes, FS , Maher, B, Pulver, AE, Shugart, YY, Valle, D, Lange, C & Nestadt, G 2015, 'Genome-wide association study in obsessive-compulsive disorder: Results from the OCGAS', Molecular psychiatry, vol. 20, no. 3, pp. 337-344. https://doi.org/10.1038/mp.2014.43

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title = "Genome-wide association study in obsessive-compulsive disorder: Results from the OCGAS",

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.",

author = "M. Mattheisen and Samuels, {J. F.} and Y. Wang and Greenberg, {B. D.} and Fyer, {A. J.} and Mccracken, {J. T.} and Geller, {D. A.} and Murphy, {D. L.} and Knowles, {J. A.} and Grados, {M. A.} and Riddle, {M. A.} and Rasmussen, {S. A.} and Mclaughlin, {N. C.} and Nurmi, {E. L.} and Askland, {K. D.} and Qin, {H. D.} and Cullen, {B. A.} and J. Piacentini and Pauls, {D. L.} and Bienvenu, {O. J.} and Stewart, {S. E.} and Liang, {K. Y.} and Goes, {F. S.} and B. Maher and Pulver, {A. E.} and Shugart, {Y. Y.} and D. Valle and C. Lange and G. Nestadt",

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doi = "10.1038/mp.2014.43",

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AU - Mattheisen, M.

AU - Samuels, J. F.

AU - Wang, Y.

AU - Greenberg, B. D.

AU - Fyer, A. J.

AU - Mccracken, J. T.

AU - Geller, D. A.

AU - Murphy, D. L.

AU - Knowles, J. A.

AU - Grados, M. A.

AU - Riddle, M. A.

AU - Rasmussen, S. A.

AU - Mclaughlin, N. C.

AU - Nurmi, E. L.

AU - Askland, K. D.

AU - Qin, H. D.

AU - Cullen, B. A.

AU - Piacentini, J.

AU - Pauls, D. L.

AU - Bienvenu, O. J.

AU - Stewart, S. E.

AU - Liang, K. Y.

AU - Goes, F. S.

AU - Maher, B.

AU - Pulver, A. E.

AU - Shugart, Y. Y.

AU - Valle, D.

AU - Lange, C.

AU - Nestadt, G.

PY - 2015/3/12

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

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