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Genome-wide association study of obsessive-compulsive disorder

(2013) MOLECULAR PSYCHIATRY. 18(7). p.788-798
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Organization
Abstract
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 x 10(-6) and P = 3.44 x 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 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 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.
Keywords
DLGAP, genetic, genomic, GWAS, neurodevelopmental disorder, obsessive-compulsive disorder, OCD COLLABORATIVE GENETICS, FAMILY-BASED ASSOCIATION, QUANTITATIVE TRAIT LOCI, TRANSPORTER GENE, LINKAGE, SLC1A1, SNPS, TWIN, REPLICATION, EXPRESSION

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Citation

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MLA
Stewart, SE, D Yu, JM Scharf, et al. “Genome-wide Association Study of Obsessive-compulsive Disorder.” MOLECULAR PSYCHIATRY 18.7 (2013): 788–798. Print.
APA
Stewart, S., Yu, D., Scharf, J., Neale, B., Fagerness, J., Mathews, C., Arnold, P., et al. (2013). Genome-wide association study of obsessive-compulsive disorder. MOLECULAR PSYCHIATRY, 18(7), 788–798.
Chicago author-date
Stewart, SE, D Yu, JM Scharf, BM Neale, JA Fagerness, CA Mathews, PD Arnold, et al. 2013. “Genome-wide Association Study of Obsessive-compulsive Disorder.” Molecular Psychiatry 18 (7): 788–798.
Chicago author-date (all authors)
Stewart, SE, D Yu, JM Scharf, BM Neale, JA Fagerness, CA Mathews, PD Arnold, PD Evans, ER Gamazon, L Osiecki, L McGrath, S Haddad, J Crane, D Hezel, C Illman, C Mayerfeld, A Konkashbaev, C Liu, A Pluzhnikov, A Tikhomirov, CK Edlund, SL Rauch, R Moessner, P Falkai, W Maier, S Ruhrmann, HJ Grabe, L Lennertz, M Wagner, L Bellodi, MC Cavallini, MA Richter, EH Cook, JL Kennedy, D Rosenberg, DJ Stein, SMJ Hemmings, C Lochner, A Azzam, DA Chavira, E Fournier, H Garrido, B Sheppard, P Umana, DL Murphy, JR Wendland, J Veenstra-VanderWeele, D Denys, R Blom, Dieter Deforce, Filip Van Nieuwerburgh, HGM Westenberg, S Walitza, K Egberts, T Renner, EC Miguel, C Cappi, AG Hounie, MC do Rosario, AS Sampaio, H Vallada, H Nicolini, N Lanzagorta, B Camarena, R Delorme, M Leboyer, CN Pato, MT Pato, E Voyiaziakis, P Heutink, DC Cath, D Posthuma, JH Smit, J Samuels, OJ Bienvenu, B Cullen, AJ Fyer, MA Grados, BD Greenberg, JT McCracken, MA Riddle, Y Wang, V Coric, JF Leckman, M Bloch, C Pittenger, V Eapen, DW Black, RA Ophoff, E Strengman, D Cusi, M Turiel, F Frau, F Macciardi, JR Gibbs, MR Cookson, A Singleton, J Hardy, AT Crenshaw, MA Parkin, DB Mirel, DV Conti, S Purcell, G Nestadt, GL Hanna, MA Jenike, JA Knowles, N Cox, and DL Pauls. 2013. “Genome-wide Association Study of Obsessive-compulsive Disorder.” Molecular Psychiatry 18 (7): 788–798.
Vancouver
1.
Stewart S, Yu D, Scharf J, Neale B, Fagerness J, Mathews C, et al. Genome-wide association study of obsessive-compulsive disorder. MOLECULAR PSYCHIATRY. 2013;18(7):788–98.
IEEE
[1]
S. Stewart et al., “Genome-wide association study of obsessive-compulsive disorder,” MOLECULAR PSYCHIATRY, vol. 18, no. 7, pp. 788–798, 2013.
@article{4241923,
  abstract     = {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 x 10(-6) and P = 3.44 x 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 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 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.},
  author       = {Stewart, SE and Yu, D and Scharf, JM and Neale, BM and Fagerness, JA and Mathews, CA and Arnold, PD and Evans, PD and Gamazon, ER and Osiecki, L and McGrath, L and Haddad, S and Crane, J and Hezel, D and Illman, C and Mayerfeld, C and Konkashbaev, A and Liu, C and Pluzhnikov, A and Tikhomirov, A and Edlund, CK and Rauch, SL and Moessner, R and Falkai, P and Maier, W and Ruhrmann, S and Grabe, HJ and Lennertz, L and Wagner, M and Bellodi, L and Cavallini, MC and Richter, MA and Cook, EH and Kennedy, JL and Rosenberg, D and Stein, DJ and Hemmings, SMJ and Lochner, C and Azzam, A and Chavira, DA and Fournier, E and Garrido, H and Sheppard, B and Umana, P and Murphy, DL and Wendland, JR and Veenstra-VanderWeele, J and Denys, D and Blom, R and Deforce, Dieter and Van Nieuwerburgh, Filip and Westenberg, HGM and Walitza, S and Egberts, K and Renner, T and Miguel, EC and Cappi, C and Hounie, AG and do Rosario, MC and Sampaio, AS and Vallada, H and Nicolini, H and Lanzagorta, N and Camarena, B and Delorme, R and Leboyer, M and Pato, CN and Pato, MT and Voyiaziakis, E and Heutink, P and Cath, DC and Posthuma, D and Smit, JH and Samuels, J and Bienvenu, OJ and Cullen, B and Fyer, AJ and Grados, MA and Greenberg, BD and McCracken, JT and Riddle, MA and Wang, Y and Coric, V and Leckman, JF and Bloch, M and Pittenger, C and Eapen, V and Black, DW and Ophoff, RA and Strengman, E and Cusi, D and Turiel, M and Frau, F and Macciardi, F and Gibbs, JR and Cookson, MR and Singleton, A and Hardy, J and Crenshaw, AT and Parkin, MA and Mirel, DB and Conti, DV and Purcell, S and Nestadt, G and Hanna, GL and Jenike, MA and Knowles, JA and Cox, N and Pauls, DL},
  issn         = {1359-4184},
  journal      = {MOLECULAR PSYCHIATRY},
  keywords     = {DLGAP,genetic,genomic,GWAS,neurodevelopmental disorder,obsessive-compulsive disorder,OCD COLLABORATIVE GENETICS,FAMILY-BASED ASSOCIATION,QUANTITATIVE TRAIT LOCI,TRANSPORTER GENE,LINKAGE,SLC1A1,SNPS,TWIN,REPLICATION,EXPRESSION},
  language     = {eng},
  number       = {7},
  pages        = {788--798},
  title        = {Genome-wide association study of obsessive-compulsive disorder},
  url          = {http://dx.doi.org/10.1038/mp.2012.85},
  volume       = {18},
  year         = {2013},
}

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