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Genome-wide association study of obsessive-compulsive disorder.

Publication ,  Journal Article
Stewart, SE; Yu, D; Scharf, JM; Neale, BM; Fagerness, JA; Mathews, CA; Arnold, PD; Evans, PD; Gamazon, ER; Davis, LK; Osiecki, L; McGrath, L ...
Published in: Mol Psychiatry
July 2013

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

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Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

July 2013

Volume

18

Issue

7

Start / End Page

788 / 798

Location

England

Related Subject Headings

  • White People
  • SAP90-PSD95 Associated Proteins
  • Quantitative Trait Loci
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Parents
  • Obsessive-Compulsive Disorder
  • Nerve Tissue Proteins
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
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Stewart, S. E., Yu, D., Scharf, J. M., Neale, B. M., Fagerness, J. A., Mathews, C. A., … Pauls, D. L. (2013). Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry, 18(7), 788–798. https://doi.org/10.1038/mp.2012.85
Stewart, S. E., D. Yu, J. M. Scharf, B. M. Neale, J. A. Fagerness, C. A. Mathews, P. D. Arnold, et al. “Genome-wide association study of obsessive-compulsive disorder.Mol Psychiatry 18, no. 7 (July 2013): 788–98. https://doi.org/10.1038/mp.2012.85.
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, et al. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry. 2013 Jul;18(7):788–98.
Stewart, S. E., et al. “Genome-wide association study of obsessive-compulsive disorder.Mol Psychiatry, vol. 18, no. 7, July 2013, pp. 788–98. Pubmed, doi:10.1038/mp.2012.85.
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, Arnold PD, Evans PD, Gamazon ER, Davis LK, Osiecki L, McGrath L, Haddad S, Crane J, Hezel D, Illman C, Mayerfeld C, Konkashbaev A, Liu C, Pluzhnikov A, Tikhomirov A, Edlund CK, Rauch SL, Moessner R, Falkai P, Maier W, Ruhrmann S, Grabe H-J, Lennertz L, Wagner M, Bellodi L, Cavallini MC, Richter MA, Cook EH, Kennedy JL, Rosenberg D, Stein DJ, Hemmings SMJ, Lochner C, Azzam A, Chavira DA, Fournier E, Garrido H, Sheppard B, Umaña P, Murphy DL, Wendland JR, Veenstra-VanderWeele J, Denys D, Blom R, Deforce D, Van Nieuwerburgh F, Westenberg HGM, Walitza S, Egberts K, Renner T, Miguel EC, Cappi C, Hounie AG, Conceição do Rosário M, Sampaio AS, Vallada H, Nicolini H, Lanzagorta N, Camarena B, Delorme R, Leboyer M, Pato CN, Pato MT, Voyiaziakis E, Heutink P, Cath DC, Posthuma D, Smit JH, Samuels J, Bienvenu OJ, Cullen B, Fyer AJ, Grados MA, Greenberg BD, McCracken JT, Riddle MA, Wang Y, Coric V, Leckman JF, Bloch M, Pittenger C, Eapen V, Black DW, Ophoff RA, Strengman E, Cusi D, Turiel M, Frau F, Macciardi F, Gibbs JR, Cookson MR, Singleton A, North American Brain Expression Consortium, Hardy J, UK Brain Expression Database, Crenshaw AT, Parkin MA, Mirel DB, Conti DV, Purcell S, Nestadt G, Hanna GL, Jenike MA, Knowles JA, Cox N, Pauls DL. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry. 2013 Jul;18(7):788–798.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

July 2013

Volume

18

Issue

7

Start / End Page

788 / 798

Location

England

Related Subject Headings

  • White People
  • SAP90-PSD95 Associated Proteins
  • Quantitative Trait Loci
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Parents
  • Obsessive-Compulsive Disorder
  • Nerve Tissue Proteins
  • Humans
  • Genome-Wide Association Study