Genome-wide association study of obsessive-compulsive disorder

S. E. Stewart; D. Yu; J. M. Scharf; B. M. Neale; J. A. Fagerness; C. A. Mathews; P. D. Arnold; P. D. Evans; E. R. Gamazon; L. Osiecki; L. McGrath; S. Haddad; J. Crane; D. Hezel; C. Illman; C. Mayerfeld; A. Konkashbaev; C. Liu; A. Pluzhnikov; A. Tikhomirov; C. K. Edlund; S. L. Rauch; R. Moessner; P. Falkai; W. Maier; S. Ruhrmann; H. J. Grabe; L. Lennertz; M. Wagner; L. Bellodi; M. C. Cavallini; M. A. Richter; E. H. Cook; J. L. Kennedy; D. Rosenberg; D. J. Stein; S. M J Hemmings; C. Lochner; A. Azzam; D. A. Chavira; E. Fournier; H. Garrido; B. Sheppard; P. Umaña; D. L. Murphy; J. R. Wendland; J. Veenstra-Vanderweele; D. Denys; R. Blom; D. Deforce; F. Van Nieuwerburgh; H. G M Westenberg; S. Walitza; K. Egberts; T. Renner; E. C. Miguel; C. Cappi; A. G. Hounie; M. Conceição Do Rosário; A. S. Sampaio; H. Vallada; H. Nicolini; N. Lanzagorta; B. Camarena; R. Delorme; M. Leboyer; C. N. Pato; M. T. Pato; E. Voyiaziakis; P. Heutink; D. C. Cath; D. Posthuma; J. H. Smit; J. Samuels; O. J. Bienvenu; B. Cullen; A. J. Fyer; M. A. Grados; B. D. Greenberg; J. T. McCracken; M. A. Riddle; Y. Wang; V. Coric; J. F. Leckman; M. Bloch; C. Pittenger; V. Eapen; D. W. Black; R. A. Ophoff; E. Strengman; D. Cusi; M. Turiel; F. Frau; F. MacCiardi; J. R. Gibbs; M. R. Cookson; A. Singleton; S. Arepalli; M. R. Cookson; A. Dillman; L. Ferrucci; J. R. Gibbs; D. G. Hernandez; R. Johnson; D. L. Longo; M. A. Nalls; R. O'Brien; A. Singleton; B. Traynor; J. Troncoso; M. Van Der Brug; H. R. Zielke; A. Zonderman; J. Hardy; A. T. Crenshaw; M. A. Parkin; D. B. Mirel; D. V. Conti; S. Purcell; G. Nestadt; G. L. Hanna; M. A. Jenike; J. A. Knowles; N. Cox; D. L. Pauls; J. A. Hardy; M. Ryten; C. Smith; D. Trabzuni; R. Walker; Mike Weale

doi:10.1038/mp.2012.85

Genome-wide association study of obsessive-compulsive disorder

S. E. Stewart, D. Yu, J. M. Scharf, B. M. Neale, J. A. Fagerness, C. A. Mathews, P. D. Arnold, P. D. Evans, E. R. Gamazon, L. Osiecki, L. McGrath, S. Haddad, J. Crane, D. Hezel, C. Illman, C. Mayerfeld, A. Konkashbaev, C. Liu, A. Pluzhnikov, A. TikhomirovC. K. Edlund, S. L. Rauch, R. Moessner, P. Falkai, W. Maier, S. Ruhrmann, H. J. Grabe, L. Lennertz, M. Wagner, L. Bellodi, M. C. Cavallini, M. A. Richter, E. H. Cook, J. L. Kennedy, D. Rosenberg, D. J. Stein, S. M J Hemmings, C. Lochner, A. Azzam, D. A. Chavira, E. Fournier, H. Garrido, B. Sheppard, P. Umaña, D. L. Murphy, J. R. Wendland, J. Veenstra-Vanderweele, D. Denys, R. Blom, D. Deforce, F. Van Nieuwerburgh, H. G M Westenberg, S. Walitza, K. Egberts, T. Renner, E. C. Miguel, C. Cappi, A. G. Hounie, M. Conceição Do Rosário, A. S. Sampaio, H. Vallada, H. Nicolini, N. Lanzagorta, B. Camarena, R. Delorme, M. Leboyer, C. N. Pato, M. T. Pato, E. Voyiaziakis, P. Heutink, D. C. Cath, D. Posthuma, J. H. Smit, J. Samuels, O. J. Bienvenu, B. Cullen, A. J. Fyer, M. A. Grados, B. D. Greenberg, J. T. McCracken, M. A. Riddle, Y. Wang, V. Coric, J. F. Leckman, M. Bloch, C. Pittenger, V. Eapen, D. W. Black, R. A. Ophoff, E. Strengman, D. Cusi, M. Turiel, F. Frau, F. MacCiardi, J. R. Gibbs, M. R. Cookson, A. Singleton, S. Arepalli, M. R. Cookson, A. Dillman, L. Ferrucci, J. R. Gibbs, D. G. Hernandez, R. Johnson, D. L. Longo, M. A. Nalls, R. O'Brien, A. Singleton, B. Traynor, J. Troncoso, M. Van Der Brug, H. R. Zielke, A. Zonderman, J. Hardy, A. T. Crenshaw, M. A. Parkin, D. B. Mirel, D. V. Conti, S. Purcell, G. Nestadt, G. L. Hanna, M. A. Jenike, J. A. Knowles, N. Cox, D. L. Pauls, J. A. Hardy, M. Ryten, C. Smith, D. Trabzuni, R. Walker, Mike Weale

Research output: Contribution to journal › Article › peer-review

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 × 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

Original language	English
Pages (from-to)	788-798
Number of pages	11
Journal	Molecular Psychiatry
Volume	18
Issue number	7
DOIs	https://doi.org/10.1038/mp.2012.85
Publication status	Published - Jul 2013

Keywords

DLGAP
genetic
genomic
GWAS
neurodevelopmental disorder
obsessive-compulsive disorder

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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10.1038/mp.2012.85

Cite this

Stewart, S. E., Yu, D., Scharf, J. M., Neale, B. M., Fagerness, J. A., Mathews, C. A., Arnold, P. D., Evans, P. D., Gamazon, E. R., Osiecki, L., McGrath, L., Haddad, S., Crane, J., Hezel, D., Illman, C., Mayerfeld, C., Konkashbaev, A., Liu, C., Pluzhnikov, A., ... Weale, M. (2013). Genome-wide association study of obsessive-compulsive disorder. Molecular Psychiatry, 18(7), 788-798. https://doi.org/10.1038/mp.2012.85

Stewart, SE, Yu, D, Scharf, JM, Neale, BM, Fagerness, JA, Mathews, CA, Arnold, PD, Evans, PD, Gamazon, ER, 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, HJ, 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, Arepalli, S, Cookson, MR, Dillman, A, Ferrucci, L, Gibbs, JR, Hernandez, DG, Johnson, R, Longo, DL, Nalls, MA, O'Brien, R, Singleton, A, Traynor, B, Troncoso, J, Van Der Brug, M, Zielke, HR, Zonderman, A, Hardy, J, Crenshaw, AT, Parkin, MA, Mirel, DB, Conti, DV, Purcell, S, Nestadt, G, Hanna, GL, Jenike, MA, Knowles, JA, Cox, N, Pauls, DL, Hardy, JA, Ryten, M, Smith, C, Trabzuni, D, Walker, R & Weale, M 2013, 'Genome-wide association study of obsessive-compulsive disorder', Molecular Psychiatry, vol. 18, no. 7, pp. 788-798. https://doi.org/10.1038/mp.2012.85

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title = "Genome-wide association study of obsessive-compulsive disorder",

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 × 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",

keywords = "DLGAP, genetic, genomic, GWAS, neurodevelopmental disorder, obsessive-compulsive disorder",

author = "Stewart, {S. E.} and D. Yu and Scharf, {J. M.} and Neale, {B. M.} and Fagerness, {J. A.} and Mathews, {C. A.} and Arnold, {P. D.} and Evans, {P. D.} and Gamazon, {E. R.} and L. Osiecki and L. McGrath and S. Haddad and J. Crane and D. Hezel and C. Illman and C. Mayerfeld and A. Konkashbaev and C. Liu and A. Pluzhnikov and A. Tikhomirov and Edlund, {C. K.} and Rauch, {S. L.} and R. Moessner and P. Falkai and W. Maier and S. Ruhrmann and Grabe, {H. J.} and L. Lennertz and M. Wagner and L. Bellodi and Cavallini, {M. C.} and Richter, {M. A.} and Cook, {E. H.} and Kennedy, {J. L.} and D. Rosenberg and Stein, {D. J.} and Hemmings, {S. M J} and C. Lochner and A. Azzam and Chavira, {D. A.} and E. Fournier and H. Garrido and B. Sheppard and P. Uma{\~n}a and Murphy, {D. L.} and Wendland, {J. R.} and J. Veenstra-Vanderweele and D. Denys and R. Blom and D. Deforce and {Van Nieuwerburgh}, F. and Westenberg, {H. G M} and S. Walitza and K. Egberts and T. Renner and Miguel, {E. C.} and C. Cappi and Hounie, {A. G.} and {Concei{\c c}{\~a}o Do Ros{\'a}rio}, M. and Sampaio, {A. S.} and H. Vallada and H. Nicolini and N. Lanzagorta and B. Camarena and R. Delorme and M. Leboyer and Pato, {C. N.} and Pato, {M. T.} and E. Voyiaziakis and P. Heutink and Cath, {D. C.} and D. Posthuma and Smit, {J. H.} and J. Samuels and Bienvenu, {O. J.} and B. Cullen and Fyer, {A. J.} and Grados, {M. A.} and Greenberg, {B. D.} and McCracken, {J. T.} and Riddle, {M. A.} and Y. Wang and V. Coric and Leckman, {J. F.} and M. Bloch and C. Pittenger and V. Eapen and Black, {D. W.} and Ophoff, {R. A.} and E. Strengman and D. Cusi and M. Turiel and F. Frau and F. MacCiardi and Gibbs, {J. R.} and Cookson, {M. R.} and A. Singleton and S. Arepalli and Cookson, {M. R.} and A. Dillman and L. Ferrucci and Gibbs, {J. R.} and Hernandez, {D. G.} and R. Johnson and Longo, {D. L.} and Nalls, {M. A.} and R. O'Brien and A. Singleton and B. Traynor and J. Troncoso and {Van Der Brug}, M. and Zielke, {H. R.} and A. Zonderman and J. Hardy and Crenshaw, {A. T.} and Parkin, {M. A.} and Mirel, {D. B.} and Conti, {D. V.} and S. Purcell and G. Nestadt and Hanna, {G. L.} and Jenike, {M. A.} and Knowles, {J. A.} and N. Cox and Pauls, {D. L.} and Hardy, {J. A.} and M. Ryten and C. Smith and D. Trabzuni and R. Walker and Mike Weale",

year = "2013",

month = jul,

doi = "10.1038/mp.2012.85",

language = "English",

volume = "18",

pages = "788--798",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "7",

}

TY - JOUR

T1 - Genome-wide association study of obsessive-compulsive disorder

AU - Stewart, S. E.

AU - Yu, D.

AU - Scharf, J. M.

AU - Neale, B. M.

AU - Fagerness, J. A.

AU - Mathews, C. A.

AU - Arnold, P. D.

AU - Evans, P. D.

AU - Gamazon, E. R.

AU - Osiecki, L.

AU - McGrath, L.

AU - Haddad, S.

AU - Crane, J.

AU - Hezel, D.

AU - Illman, C.

AU - Mayerfeld, C.

AU - Konkashbaev, A.

AU - Liu, C.

AU - Pluzhnikov, A.

AU - Tikhomirov, A.

AU - Edlund, C. K.

AU - Rauch, S. L.

AU - Moessner, R.

AU - Falkai, P.

AU - Maier, W.

AU - Ruhrmann, S.

AU - Grabe, H. J.

AU - Lennertz, L.

AU - Wagner, M.

AU - Bellodi, L.

AU - Cavallini, M. C.

AU - Richter, M. A.

AU - Cook, E. H.

AU - Kennedy, J. L.

AU - Rosenberg, D.

AU - Stein, D. J.

AU - Hemmings, S. M J

AU - Lochner, C.

AU - Azzam, A.

AU - Chavira, D. A.

AU - Fournier, E.

AU - Garrido, H.

AU - Sheppard, B.

AU - Umaña, P.

AU - Murphy, D. L.

AU - Wendland, J. R.

AU - Veenstra-Vanderweele, J.

AU - Denys, D.

AU - Blom, R.

AU - Deforce, D.

AU - Van Nieuwerburgh, F.

AU - Westenberg, H. G M

AU - Walitza, S.

AU - Egberts, K.

AU - Renner, T.

AU - Miguel, E. C.

AU - Cappi, C.

AU - Hounie, A. G.

AU - Conceição Do Rosário, M.

AU - Sampaio, A. S.

AU - Vallada, H.

AU - Nicolini, H.

AU - Lanzagorta, N.

AU - Camarena, B.

AU - Delorme, R.

AU - Leboyer, M.

AU - Pato, C. N.

AU - Pato, M. T.

AU - Voyiaziakis, E.

AU - Heutink, P.

AU - Cath, D. C.

AU - Posthuma, D.

AU - Smit, J. H.

AU - Samuels, J.

AU - Bienvenu, O. J.

AU - Cullen, B.

AU - Fyer, A. J.

AU - Grados, M. A.

AU - Greenberg, B. D.

AU - McCracken, J. T.

AU - Riddle, M. A.

AU - Wang, Y.

AU - Coric, V.

AU - Leckman, J. F.

AU - Bloch, M.

AU - Pittenger, C.

AU - Eapen, V.

AU - Black, D. W.

AU - Ophoff, R. A.

AU - Strengman, E.

AU - Cusi, D.

AU - Turiel, M.

AU - Frau, F.

AU - MacCiardi, F.

AU - Gibbs, J. R.

AU - Cookson, M. R.

AU - Singleton, A.

AU - Arepalli, S.

AU - Cookson, M. R.

AU - Dillman, A.

AU - Ferrucci, L.

AU - Gibbs, J. R.

AU - Hernandez, D. G.

AU - Johnson, R.

AU - Longo, D. L.

AU - Nalls, M. A.

AU - O'Brien, R.

AU - Singleton, A.

AU - Traynor, B.

AU - Troncoso, J.

AU - Van Der Brug, M.

AU - Zielke, H. R.

AU - Zonderman, A.

AU - Hardy, J.

AU - Crenshaw, A. T.

AU - Parkin, M. A.

AU - Mirel, D. B.

AU - Conti, D. V.

AU - Purcell, S.

AU - Nestadt, G.

AU - Hanna, G. L.

AU - Jenike, M. A.

AU - Knowles, J. A.

AU - Cox, N.

AU - Pauls, D. L.

AU - Hardy, J. A.

AU - Ryten, M.

AU - Smith, C.

AU - Trabzuni, D.

AU - Walker, R.

AU - Weale, Mike

PY - 2013/7

Y1 - 2013/7

N2 - 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

AB - 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

KW - DLGAP

KW - genetic

KW - genomic

KW - GWAS

KW - neurodevelopmental disorder

KW - obsessive-compulsive disorder

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U2 - 10.1038/mp.2012.85

DO - 10.1038/mp.2012.85

M3 - Article

C2 - 22889921

AN - SCOPUS:84879422520

SN - 1359-4184

VL - 18

SP - 788

EP - 798

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 7

ER -

Genome-wide association study of obsessive-compulsive disorder

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