Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

D.M. Yu; C.A. Mathews; J.M. Scharf; B.M. Neale; L.K. Davis; E.R. Gamazon; E.M. Derks; P. Evans; C.K. Edlund; J. Crane; L. Osiecki; P. Gallagher; G. Gerber; S. Haddad; C. Illmann; L.M. McGrath; C. Mayerfeld; S. Arepalli; C. Barlassina; C.L. Barr; L. Bellodi; F. Benarroch; G.B. Berrio; O.J. Bienvenu; D.W. Black; M.H. Bloch; H. Brentani; R.D. Bruun; C.L. Budman; B. Camarena; D.D. Campbell; C. Cappi; J.C.C. Silgado; M.C. Cavallini; D.A. Chavira; S. Chouinard; E.H. Cook; M.R. Cookson; V. Coric; B. Cullen; D. Cusi; R. Delorme; D. Denys; Y. Dion; V. Eapen; K. Egberts; P. Falkai; T. Fernandez; E. Fournier; H. Garrido; D. Geller; D.L. Gilbert; S.L. Girard; H.J. Grabe; M.A. Grados; B.D. Greenberg; V. Gross-Tsur; E. Grunblatt; J. Hardy; G.A. Heiman; S.M.J. Hemmings; L.D. Herrera; D.M. Hezel; P.J. Hoekstra; J. Jankovic; J.L. Kennedy; R.A. King; A.I. Konkashbaev; B. Kremeyer; R. Kurlan; N. Lanzagorta; M. Leboyer; J.F. Leckman; L. Lennertz; C.Y. Liu; C. Lochner; T.L. Lowe; S. Lupoli; F. Macciardi; W. Maier; P. Manunta; M. Marconi; J.T. McCracken; S.C.M. Restrepo; R. Moessner; P. Moorjani; J. Morgan; H. Muller; D.L. Murphy; A.L. Naarden; E. Nurmi; W.C. Ochoa; R. A. Ophoff; A.J. Pakstis; M.T. Pato; C.N. Pato; J. Piacentini; C. Pittenger; Y. Pollak; J.H. Smit; D. Posthuma; N.J. Cox; D.L. Pauls

doi:10.1176/appi.ajp.2014.13101306

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

D.M. Yu, C.A. Mathews, J.M. Scharf, B.M. Neale, L.K. Davis, E.R. Gamazon, E.M. Derks, P. Evans, C.K. Edlund, J. Crane, L. Osiecki, P. Gallagher, G. Gerber, S. Haddad, C. Illmann, L.M. McGrath, C. Mayerfeld, S. Arepalli, C. Barlassina, C.L. BarrL. Bellodi, F. Benarroch, G.B. Berrio, O.J. Bienvenu, D.W. Black, M.H. Bloch, H. Brentani, R.D. Bruun, C.L. Budman, B. Camarena, D.D. Campbell, C. Cappi, J.C.C. Silgado, M.C. Cavallini, D.A. Chavira, S. Chouinard, E.H. Cook, M.R. Cookson, V. Coric, B. Cullen, D. Cusi, R. Delorme, D. Denys, Y. Dion, V. Eapen, K. Egberts, P. Falkai, T. Fernandez, E. Fournier, H. Garrido, D. Geller, D.L. Gilbert, S.L. Girard, H.J. Grabe, M.A. Grados, B.D. Greenberg, V. Gross-Tsur, E. Grunblatt, J. Hardy, G.A. Heiman, S.M.J. Hemmings, L.D. Herrera, D.M. Hezel, P.J. Hoekstra, J. Jankovic, J.L. Kennedy, R.A. King, A.I. Konkashbaev, B. Kremeyer, R. Kurlan, N. Lanzagorta, M. Leboyer, J.F. Leckman, L. Lennertz, C.Y. Liu, C. Lochner, T.L. Lowe, S. Lupoli, F. Macciardi, W. Maier, P. Manunta, M. Marconi, J.T. McCracken, S.C.M. Restrepo, R. Moessner, P. Moorjani, J. Morgan, H. Muller, D.L. Murphy, A.L. Naarden, E. Nurmi, W.C. Ochoa, R. A. Ophoff, A.J. Pakstis, M.T. Pato, C.N. Pato, J. Piacentini, C. Pittenger, Y. Pollak, J.H. Smit, D. Posthuma, N.J. Cox, D.L. Pauls

Complex Trait Genetics

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identi fication of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted aGWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide signi ficance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2x10

Original language	English
Pages (from-to)	82-93
Journal	American Journal of Psychiatry
Volume	172
Issue number	1
DOIs	https://doi.org/10.1176/appi.ajp.2014.13101306
Publication status	Published - 2015

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Yu, D. M., Mathews, C. A., Scharf, J. M., Neale, B. M., Davis, L. K., Gamazon, E. R., Derks, E. M., Evans, P., Edlund, C. K., Crane, J., Osiecki, L., Gallagher, P., Gerber, G., Haddad, S., Illmann, C., McGrath, L. M., Mayerfeld, C., Arepalli, S., Barlassina, C., ... Pauls, D. L. (2015). Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD. American Journal of Psychiatry, 172(1), 82-93. https://doi.org/10.1176/appi.ajp.2014.13101306

@article{a085fb55d295403cb9f8710303d88e15,

title = "Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD",

abstract = "Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identi fication of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted aGWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide signi ficance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2x10",

author = "D.M. Yu and C.A. Mathews and J.M. Scharf and B.M. Neale and L.K. Davis and E.R. Gamazon and E.M. Derks and P. Evans and C.K. Edlund and J. Crane and L. Osiecki and P. Gallagher and G. Gerber and S. Haddad and C. Illmann and L.M. McGrath and C. Mayerfeld and S. Arepalli and C. Barlassina and C.L. Barr and L. Bellodi and F. Benarroch and G.B. Berrio and O.J. Bienvenu and D.W. Black and M.H. Bloch and H. Brentani and R.D. Bruun and C.L. Budman and B. Camarena and D.D. Campbell and C. Cappi and J.C.C. Silgado and M.C. Cavallini and D.A. Chavira and S. Chouinard and E.H. Cook and M.R. Cookson and V. Coric and B. Cullen and D. Cusi and R. Delorme and D. Denys and Y. Dion and V. Eapen and K. Egberts and P. Falkai and T. Fernandez and E. Fournier and H. Garrido and D. Geller and D.L. Gilbert and S.L. Girard and H.J. Grabe and M.A. Grados and B.D. Greenberg and V. Gross-Tsur and E. Grunblatt and J. Hardy and G.A. Heiman and S.M.J. Hemmings and L.D. Herrera and D.M. Hezel and P.J. Hoekstra and J. Jankovic and J.L. Kennedy and R.A. King and A.I. Konkashbaev and B. Kremeyer and R. Kurlan and N. Lanzagorta and M. Leboyer and J.F. Leckman and L. Lennertz and C.Y. Liu and C. Lochner and T.L. Lowe and S. Lupoli and F. Macciardi and W. Maier and P. Manunta and M. Marconi and J.T. McCracken and S.C.M. Restrepo and R. Moessner and P. Moorjani and J. Morgan and H. Muller and D.L. Murphy and A.L. Naarden and E. Nurmi and W.C. Ochoa and Ophoff, {R. A.} and A.J. Pakstis and M.T. Pato and C.N. Pato and J. Piacentini and C. Pittenger and Y. Pollak and J.H. Smit and D. Posthuma and N.J. Cox and D.L. Pauls",

year = "2015",

doi = "10.1176/appi.ajp.2014.13101306",

language = "English",

volume = "172",

pages = "82--93",

journal = "American Journal of Psychiatry",

issn = "0002-953X",

publisher = "American Psychiatric Association",

number = "1",

}

Yu, DM, Mathews, CA, Scharf, JM, Neale, BM, Davis, LK, Gamazon, ER, Derks, EM, Evans, P, Edlund, CK, Crane, J, Osiecki, L, Gallagher, P, Gerber, G, Haddad, S, Illmann, C, McGrath, LM, Mayerfeld, C, Arepalli, S, Barlassina, C, Barr, CL, Bellodi, L, Benarroch, F, Berrio, GB, Bienvenu, OJ, Black, DW, Bloch, MH, Brentani, H, Bruun, RD, Budman, CL, Camarena, B, Campbell, DD, Cappi, C, Silgado, JCC, Cavallini, MC, Chavira, DA, Chouinard, S, Cook, EH, Cookson, MR, Coric, V, Cullen, B, Cusi, D, Delorme, R, Denys, D, Dion, Y, Eapen, V, Egberts, K, Falkai, P, Fernandez, T, Fournier, E, Garrido, H, Geller, D, Gilbert, DL, Girard, SL, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Grunblatt, E, Hardy, J, Heiman, GA, Hemmings, SMJ, Herrera, LD, Hezel, DM, Hoekstra, PJ, Jankovic, J, Kennedy, JL, King, RA, Konkashbaev, AI, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Liu, CY, Lochner, C, Lowe, TL, Lupoli, S, Macciardi, F, Maier, W, Manunta, P, Marconi, M, McCracken, JT, Restrepo, SCM, Moessner, R, Moorjani, P, Morgan, J, Muller, H, Murphy, DL, Naarden, AL, Nurmi, E, Ochoa, WC, Ophoff, RA, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Smit, JH, Posthuma, D, Cox, NJ & Pauls, DL 2015, 'Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD', American Journal of Psychiatry, vol. 172, no. 1, pp. 82-93. https://doi.org/10.1176/appi.ajp.2014.13101306

TY - JOUR

T1 - Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

AU - Yu, D.M.

AU - Mathews, C.A.

AU - Scharf, J.M.

AU - Neale, B.M.

AU - Davis, L.K.

AU - Gamazon, E.R.

AU - Derks, E.M.

AU - Evans, P.

AU - Edlund, C.K.

AU - Crane, J.

AU - Osiecki, L.

AU - Gallagher, P.

AU - Gerber, G.

AU - Haddad, S.

AU - Illmann, C.

AU - McGrath, L.M.

AU - Mayerfeld, C.

AU - Arepalli, S.

AU - Barlassina, C.

AU - Barr, C.L.

AU - Bellodi, L.

AU - Benarroch, F.

AU - Berrio, G.B.

AU - Bienvenu, O.J.

AU - Black, D.W.

AU - Bloch, M.H.

AU - Brentani, H.

AU - Bruun, R.D.

AU - Budman, C.L.

AU - Camarena, B.

AU - Campbell, D.D.

AU - Cappi, C.

AU - Silgado, J.C.C.

AU - Cavallini, M.C.

AU - Chavira, D.A.

AU - Chouinard, S.

AU - Cook, E.H.

AU - Cookson, M.R.

AU - Coric, V.

AU - Cullen, B.

AU - Cusi, D.

AU - Delorme, R.

AU - Denys, D.

AU - Dion, Y.

AU - Eapen, V.

AU - Egberts, K.

AU - Falkai, P.

AU - Fernandez, T.

AU - Fournier, E.

AU - Garrido, H.

AU - Geller, D.

AU - Gilbert, D.L.

AU - Girard, S.L.

AU - Grabe, H.J.

AU - Grados, M.A.

AU - Greenberg, B.D.

AU - Gross-Tsur, V.

AU - Grunblatt, E.

AU - Hardy, J.

AU - Heiman, G.A.

AU - Hemmings, S.M.J.

AU - Herrera, L.D.

AU - Hezel, D.M.

AU - Hoekstra, P.J.

AU - Jankovic, J.

AU - Kennedy, J.L.

AU - King, R.A.

AU - Konkashbaev, A.I.

AU - Kremeyer, B.

AU - Kurlan, R.

AU - Lanzagorta, N.

AU - Leboyer, M.

AU - Leckman, J.F.

AU - Lennertz, L.

AU - Liu, C.Y.

AU - Lochner, C.

AU - Lowe, T.L.

AU - Lupoli, S.

AU - Macciardi, F.

AU - Maier, W.

AU - Manunta, P.

AU - Marconi, M.

AU - McCracken, J.T.

AU - Restrepo, S.C.M.

AU - Moessner, R.

AU - Moorjani, P.

AU - Morgan, J.

AU - Muller, H.

AU - Murphy, D.L.

AU - Naarden, A.L.

AU - Nurmi, E.

AU - Ochoa, W.C.

AU - Ophoff, R. A.

AU - Pakstis, A.J.

AU - Pato, M.T.

AU - Pato, C.N.

AU - Piacentini, J.

AU - Pittenger, C.

AU - Pollak, Y.

AU - Smit, J.H.

AU - Posthuma, D.

AU - Cox, N.J.

AU - Pauls, D.L.

PY - 2015

Y1 - 2015

N2 - Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identi fication of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted aGWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide signi ficance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2x10

AB - Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identi fication of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted aGWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide signi ficance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2x10

U2 - 10.1176/appi.ajp.2014.13101306

DO - 10.1176/appi.ajp.2014.13101306

M3 - Article

SN - 0002-953X

VL - 172

SP - 82

EP - 93

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

IS - 1

ER -

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

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