Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

C O'Dushlaine; L Rossin; PH Lee; L Duncan; NN Parikshak; S Newhouse; S Ripke; BM Neale; SM Purcell; Daniëlle Posthuma; JI Nurnberger; SH Lee; SV Faraone; RH Perlis; BJ Mowry; A Thapar; ME Goddard; JS Witte; D Absher; I Agartz; H Akil; F Amin; OA Andreassen; A Anjorin; R Anney; V Anttila; DE Arking; P Asherson; MH Azevedo; L Backlund; JA Badner; AJ Bailey; T Banaschewski; JD Barchas; MR Barnes; TB Barrett; N Bass; A Battaglia; M Bauer; M Bayes; F Bellivier; SE Bergen; W Berrettini; C Betancur; T Bettecken; J Biederman; EB Binder; DW Black; DHR Blackwood; CS Bloss; M Boehnke; DI Boomsma; R Breuer; R Bruggeman; P Cormican; NG Buccola; JK Buitelaar; WE Bunney; JD Buxbaum; WF Byerley; EM Byrne; S Caesar; W Cahn; RM Cantor; Maria Casas Sanahuja; A Chakravarti; K Chambert; K Choudhury; S Cichon; M Mattheisen; CR Cloninger; DA Collier; EH Cook; H Coon; B Cormand; A Corvin; WH Coryell; DW Craig; IW Craig; J Crosbie; ML Cuccaro; D Curtis; D Czamara; S Datta; G Dawson; R Day; EJ de Geus; F Degenhardt; S Djurovic; GJ Donohoe; AE Doyle; J Duan; F Dudbridge; E Duketis; RP Ebstein; HJ Edenberg; J Elia; S Ennis; B Etain; A Fanous; AE Farmer; IN Ferrier; M Flicldnger; E Fombonne; T Foroud; J Frank; B Franke; C Fraser; R Freedman; NB Freimer; CM Freitag; M Friedl; L Frisen; L Gailagher; PV Gejman; L Georgieva; ES Gershon; I Giegling; M Gill; SD Gordon; K Gordon-Smith; EK Green; TA Greenwood; DE Grice; M Gross; D Grozeva; W Guan; H Gurling; L de Haan; JL Haines; H Hakonarson; J Hallmayer; SP Hamilton; ML Hamshere; TF Hansen; AM Hartmann; M Hautzinger; AC Heath; AK Henders; S Herms; IB Hickie; M Hipolito; S Hoefels; F Holsboer; Witte Hoogendijk; JJ (Jouke Jan) Hottenga; CM Hultman; V Hus; A Ingason; M Ising; S Jamain; EG Jones; I Jones; L Jones; JY Tzeng; AK Kahler; RS Kahn; R Kandaswamy; MC Keller; JL Kennedy; E Kenny; L Kent; YJ Kim; GK Kirov; SM Klauck; L Klei; JA Knowles; MA Kohli; DL Koller; B Konte; A Korszun; L Krabbendam; R Krasucki; J Kuntsi; P Kwan; M Landen; N Langstrom; M Lathrop; J Lawrence; WB Lawson; M Leboyer; DH Ledbetter; T Lencz; KP Lesch; DF Levinson; CM Lewis; Juan Li; P Lichtenstein; JA Lieberman; DY Lin; DH Linszen; CY Liu; FW Lohoff; SK Loo; C Lord; JK Lowe; S Lucae; DJ MacIntyre; PAF Madden; E Maestrini; PKE Magnusson; PB Mahon; W Maier; AK Malhotra; SM Mane; CL Martin; NG Martin; K Matthews; M Mattingsdal; SA McCarroll; KA McGhee; JJ McGough; PJ McGrath; P McGuffin; MG McInnis; A McIntosh; R McKinney; AW McLean; FJ McMahon; WM McMahon; A McQuillin; H Medeiros; SE Medland; S Meier; I Melle; F Meng; J Meyer; CM (Christel) Middeldorp; L Middleton; V Milanova; A Miranda; AP Monaco; GW Montgomery; JL Moran; D Moreno-De-Luca; G Morken; DW Morris; EM Morrow; V Moskvina; P Muglia; TW Muhleisen; WJ Muir; B Muller-Myhsok; M Murtha; RM Myers; I Myin-Germeys; MC Neale; SF Nelson; CM Nievergelt; I Nikolov; V Nimgaonkar; WA Nolen; MM Nothen; EA Nwulia; DR Nyholt; RD Oades; A Olincy; G Oliveira; L Olsen; RA Ophoff; U Osby; MJ Owen; A Palotie; JR Parr; AD Paterson; CN Pato; MT Pato; BW Penninx; ML Pergadia; MA Pericak-Vance; BS Pickard; J Pimm; J Piven; JB Potash; F Poustka; P Propping; V Puri; DJ Quested; EM Quinn; JA Ramos-Quiroga; HB Rasmussen; S Raychaudhuri; K Rehnstrom; A Reif; M Ribases; JP Rice; M Rietschel; K Roeder; H Roeyers; A Rothenberger; G Rouleau; D Ruderfer; D Rujescu; AR Sanders; SJ Sanders; SL Santangelo; JA Sergeant; R Schachar; M Schalling; AF Schatzberg; WA Scheftner; GD Schellenberg; SW Scherer; NJ Schork; TG Schulze; J Schumacher; M Schwarz; E Scolnick; LJ Scott; JX Shi; PD Shilling; SI Shyn; JM Silverman; SL Slager; SL Smalley; JH Smit; EN Smith; EJS Sonuga-Barke; DS Cair; M State; M Steffens; HC Steinhausen; JS Strauss; J Strohmaier; TS Stroup; JS Sutdiffe; P Szatmari; S Szelinger; S Thirumalai; RC Thompson; AA Todorov; F Tozzi; J Treutlein; M Uhr; EJCG (Edwin) van den Oord; G Van Grootheest; J van Os; AM Vicente; VJ Vieland; JB Vincent; PM Visscher; CA Walsh; TH Wassink; SJ Watson; MM Weissman; T Werge; TF Wienker; EM Wijsman; G Willemsen; N Williams; AJ Willsey; SH Witt; W Xu; AH Young; TW Yu; S Zammit; PP Zandi; P (Ping) Zhang; FG Zitman; S Zollner; B Devlin; JR Kelsoe; P Sklar; MJ Daly; MC O'Donovan; N Craddock; KS Kendler; LA Weiss; NR Wray; ZM Zhao; DH Geschwind; PF Sullivan; JW Smoller; PA Holmans; G Breen

doi:10.1038/nn.3922

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

C O'Dushlaine, L Rossin, PH Lee, L Duncan, NN Parikshak, S Newhouse, S Ripke, BM Neale, SM Purcell, Daniëlle Posthuma, JI Nurnberger, SH Lee, SV Faraone, RH Perlis, BJ Mowry, A Thapar, ME Goddard, JS Witte, D Absher, I AgartzH Akil, F Amin, OA Andreassen, A Anjorin, R Anney, V Anttila, DE Arking, P Asherson, MH Azevedo, L Backlund, JA Badner, AJ Bailey, T Banaschewski, JD Barchas, MR Barnes, TB Barrett, N Bass, A Battaglia, M Bauer, M Bayes, F Bellivier, SE Bergen, W Berrettini, C Betancur, T Bettecken, J Biederman, EB Binder, DW Black, DHR Blackwood, CS Bloss, M Boehnke, DI Boomsma, R Breuer, R Bruggeman, P Cormican, NG Buccola, JK Buitelaar, WE Bunney, JD Buxbaum, WF Byerley, EM Byrne, S Caesar, W Cahn, RM Cantor, Maria Casas Sanahuja, A Chakravarti, K Chambert, K Choudhury, S Cichon, M Mattheisen, CR Cloninger, DA Collier, EH Cook, H Coon, B Cormand, A Corvin, WH Coryell, DW Craig, IW Craig, J Crosbie, ML Cuccaro, D Curtis, D Czamara, S Datta, G Dawson, R Day, EJ de Geus, F Degenhardt, S Djurovic, GJ Donohoe, AE Doyle, J Duan, F Dudbridge, E Duketis, RP Ebstein, HJ Edenberg, J Elia, S Ennis, B Etain, A Fanous, AE Farmer, IN Ferrier, M Flicldnger, E Fombonne, T Foroud, J Frank, B Franke, C Fraser, R Freedman, NB Freimer, CM Freitag, M Friedl, L Frisen, L Gailagher, PV Gejman, L Georgieva, ES Gershon, I Giegling, M Gill, SD Gordon, K Gordon-Smith, EK Green, TA Greenwood, DE Grice, M Gross, D Grozeva, W Guan, H Gurling, L de Haan, JL Haines, H Hakonarson, J Hallmayer, SP Hamilton, ML Hamshere, TF Hansen, AM Hartmann, M Hautzinger, AC Heath, AK Henders, S Herms, IB Hickie, M Hipolito, S Hoefels, F Holsboer, Witte Hoogendijk, JJ (Jouke Jan) Hottenga, CM Hultman, V Hus, A Ingason, M Ising, S Jamain, EG Jones, I Jones, L Jones, JY Tzeng, AK Kahler, RS Kahn, R Kandaswamy, MC Keller, JL Kennedy, E Kenny, L Kent, YJ Kim, GK Kirov, SM Klauck, L Klei, JA Knowles, MA Kohli, DL Koller, B Konte, A Korszun, L Krabbendam, R Krasucki, J Kuntsi, P Kwan, M Landen, N Langstrom, M Lathrop, J Lawrence, WB Lawson, M Leboyer, DH Ledbetter, T Lencz, KP Lesch, DF Levinson, CM Lewis, Juan Li, P Lichtenstein, JA Lieberman, DY Lin, DH Linszen, CY Liu, FW Lohoff, SK Loo, C Lord, JK Lowe, S Lucae, DJ MacIntyre, PAF Madden, E Maestrini, PKE Magnusson, PB Mahon, W Maier, AK Malhotra, SM Mane, CL Martin, NG Martin, K Matthews, M Mattingsdal, SA McCarroll, KA McGhee, JJ McGough, PJ McGrath, P McGuffin, MG McInnis, A McIntosh, R McKinney, AW McLean, FJ McMahon, WM McMahon, A McQuillin, H Medeiros, SE Medland, S Meier, I Melle, F Meng, J Meyer, CM (Christel) Middeldorp, L Middleton, V Milanova, A Miranda, AP Monaco, GW Montgomery, JL Moran, D Moreno-De-Luca, G Morken, DW Morris, EM Morrow, V Moskvina, P Muglia, TW Muhleisen, WJ Muir, B Muller-Myhsok, M Murtha, RM Myers, I Myin-Germeys, MC Neale, SF Nelson, CM Nievergelt, I Nikolov, V Nimgaonkar, WA Nolen, MM Nothen, EA Nwulia, DR Nyholt, RD Oades, A Olincy, G Oliveira, L Olsen, RA Ophoff, U Osby, MJ Owen, A Palotie, JR Parr, AD Paterson, CN Pato, MT Pato, BW Penninx, ML Pergadia, MA Pericak-Vance, BS Pickard, J Pimm, J Piven, JB Potash, F Poustka, P Propping, V Puri, DJ Quested, EM Quinn, JA Ramos-Quiroga, HB Rasmussen, S Raychaudhuri, K Rehnstrom, A Reif, M Ribases, JP Rice, M Rietschel, K Roeder, H Roeyers, A Rothenberger, G Rouleau, D Ruderfer, D Rujescu, AR Sanders, SJ Sanders, SL Santangelo, JA Sergeant, R Schachar, M Schalling, AF Schatzberg, WA Scheftner, GD Schellenberg, SW Scherer, NJ Schork, TG Schulze, J Schumacher, M Schwarz, E Scolnick, LJ Scott, JX Shi, PD Shilling, SI Shyn, JM Silverman, SL Slager, SL Smalley, JH Smit, EN Smith, EJS Sonuga-Barke, DS Cair, M State, M Steffens, HC Steinhausen, JS Strauss, J Strohmaier, TS Stroup, JS Sutdiffe, P Szatmari, S Szelinger, S Thirumalai, RC Thompson, AA Todorov, F Tozzi, J Treutlein, M Uhr, EJCG (Edwin) van den Oord, G Van Grootheest, J van Os, AM Vicente, VJ Vieland, JB Vincent, PM Visscher, CA Walsh, TH Wassink, SJ Watson, MM Weissman, T Werge, TF Wienker, EM Wijsman, G Willemsen, N Williams, AJ Willsey, SH Witt, W Xu, AH Young, TW Yu, S Zammit, PP Zandi, P (Ping) Zhang, FG Zitman, S Zollner, B Devlin, JR Kelsoe, P Sklar, MJ Daly, MC O'Donovan, N Craddock, KS Kendler, LA Weiss, NR Wray, ZM Zhao, DH Geschwind, PF Sullivan, JW Smoller, PA Holmans, G Breen

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

543 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Original language	Undefined/Unknown
Pages (from-to)	199-209
Number of pages	11
Journal	Nature Neuroscience
Volume	18
Issue number	2
DOIs	https://doi.org/10.1038/nn.3922
Publication status	Published - 2015

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10.1038/nn.3922

Cite this

O'Dushlaine, C., Rossin, L., Lee, PH., Duncan, L., Parikshak, NN., Newhouse, S., Ripke, S., Neale, BM., Purcell, SM., Posthuma, D., Nurnberger, JI., Lee, SH., Faraone, SV., Perlis, RH., Mowry, BJ., Thapar, A., Goddard, ME., Witte, JS., Absher, D., ... Breen, G. (2015). Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nature Neuroscience, 18(2), 199-209. https://doi.org/10.1038/nn.3922

@article{0e36f7ee24c74e29ba7c55a580374530,

title = "Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways",

abstract = "Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.",

author = "C O'Dushlaine and L Rossin and PH Lee and L Duncan and NN Parikshak and S Newhouse and S Ripke and BM Neale and SM Purcell and Dani{\"e}lle Posthuma and JI Nurnberger and SH Lee and SV Faraone and RH Perlis and BJ Mowry and A Thapar and ME Goddard and JS Witte and D Absher and I Agartz and H Akil and F Amin and OA Andreassen and A Anjorin and R Anney and V Anttila and DE Arking and P Asherson and MH Azevedo and L Backlund and JA Badner and AJ Bailey and T Banaschewski and JD Barchas and MR Barnes and TB Barrett and N Bass and A Battaglia and M Bauer and M Bayes and F Bellivier and SE Bergen and W Berrettini and C Betancur and T Bettecken and J Biederman and EB Binder and DW Black and DHR Blackwood and CS Bloss and M Boehnke and DI Boomsma and R Breuer and R Bruggeman and P Cormican and NG Buccola and JK Buitelaar and WE Bunney and JD Buxbaum and WF Byerley and EM Byrne and S Caesar and W Cahn and RM Cantor and {Casas Sanahuja}, Maria and A Chakravarti and K Chambert and K Choudhury and S Cichon and M Mattheisen and CR Cloninger and DA Collier and EH Cook and H Coon and B Cormand and A Corvin and WH Coryell and DW Craig and IW Craig and J Crosbie and ML Cuccaro and D Curtis and D Czamara and S Datta and G Dawson and R Day and {de Geus}, EJ and F Degenhardt and S Djurovic and GJ Donohoe and AE Doyle and J Duan and F Dudbridge and E Duketis and RP Ebstein and HJ Edenberg and J Elia and S Ennis and B Etain and A Fanous and AE Farmer and IN Ferrier and M Flicldnger and E Fombonne and T Foroud and J Frank and B Franke and C Fraser and R Freedman and NB Freimer and CM Freitag and M Friedl and L Frisen and L Gailagher and PV Gejman and L Georgieva and ES Gershon and I Giegling and M Gill and SD Gordon and K Gordon-Smith and EK Green and TA Greenwood and DE Grice and M Gross and D Grozeva and W Guan and H Gurling and {de Haan}, L and JL Haines and H Hakonarson and J Hallmayer and SP Hamilton and ML Hamshere and TF Hansen and AM Hartmann and M Hautzinger and AC Heath and AK Henders and S Herms and IB Hickie and M Hipolito and S Hoefels and F Holsboer and Witte Hoogendijk and Hottenga, {JJ (Jouke Jan)} and CM Hultman and V Hus and A Ingason and M Ising and S Jamain and EG Jones and I Jones and L Jones and JY Tzeng and AK Kahler and RS Kahn and R Kandaswamy and MC Keller and JL Kennedy and E Kenny and L Kent and YJ Kim and GK Kirov and SM Klauck and L Klei and JA Knowles and MA Kohli and DL Koller and B Konte and A Korszun and L Krabbendam and R Krasucki and J Kuntsi and P Kwan and M Landen and N Langstrom and M Lathrop and J Lawrence and WB Lawson and M Leboyer and DH Ledbetter and T Lencz and KP Lesch and DF Levinson and CM Lewis and Juan Li and P Lichtenstein and JA Lieberman and DY Lin and DH Linszen and CY Liu and FW Lohoff and SK Loo and C Lord and JK Lowe and S Lucae and DJ MacIntyre and PAF Madden and E Maestrini and PKE Magnusson and PB Mahon and W Maier and AK Malhotra and SM Mane and CL Martin and NG Martin and K Matthews and M Mattingsdal and SA McCarroll and KA McGhee and JJ McGough and PJ McGrath and P McGuffin and MG McInnis and A McIntosh and R McKinney and AW McLean and FJ McMahon and WM McMahon and A McQuillin and H Medeiros and SE Medland and S Meier and I Melle and F Meng and J Meyer and Middeldorp, {CM (Christel)} and L Middleton and V Milanova and A Miranda and AP Monaco and GW Montgomery and JL Moran and D Moreno-De-Luca and G Morken and DW Morris and EM Morrow and V Moskvina and P Muglia and TW Muhleisen and WJ Muir and B Muller-Myhsok and M Murtha and RM Myers and I Myin-Germeys and MC Neale and SF Nelson and CM Nievergelt and I Nikolov and V Nimgaonkar and WA Nolen and MM Nothen and EA Nwulia and DR Nyholt and RD Oades and A Olincy and G Oliveira and L Olsen and RA Ophoff and U Osby and MJ Owen and A Palotie and JR Parr and AD Paterson and CN Pato and MT Pato and BW Penninx and ML Pergadia and MA Pericak-Vance and BS Pickard and J Pimm and J Piven and JB Potash and F Poustka and P Propping and V Puri and DJ Quested and EM Quinn and JA Ramos-Quiroga and HB Rasmussen and S Raychaudhuri and K Rehnstrom and A Reif and M Ribases and JP Rice and M Rietschel and K Roeder and H Roeyers and A Rothenberger and G Rouleau and D Ruderfer and D Rujescu and AR Sanders and SJ Sanders and SL Santangelo and JA Sergeant and R Schachar and M Schalling and AF Schatzberg and WA Scheftner and GD Schellenberg and SW Scherer and NJ Schork and TG Schulze and J Schumacher and M Schwarz and E Scolnick and LJ Scott and JX Shi and PD Shilling and SI Shyn and JM Silverman and SL Slager and SL Smalley and JH Smit and EN Smith and EJS Sonuga-Barke and DS Cair and M State and M Steffens and HC Steinhausen and JS Strauss and J Strohmaier and TS Stroup and JS Sutdiffe and P Szatmari and S Szelinger and S Thirumalai and RC Thompson and AA Todorov and F Tozzi and J Treutlein and M Uhr and {van den Oord}, {EJCG (Edwin)} and {Van Grootheest}, G and {van Os}, J and AM Vicente and VJ Vieland and JB Vincent and PM Visscher and CA Walsh and TH Wassink and SJ Watson and MM Weissman and T Werge and TF Wienker and EM Wijsman and G Willemsen and N Williams and AJ Willsey and SH Witt and W Xu and AH Young and TW Yu and S Zammit and PP Zandi and Zhang, {P (Ping)} and FG Zitman and S Zollner and B Devlin and JR Kelsoe and P Sklar and MJ Daly and MC O'Donovan and N Craddock and KS Kendler and LA Weiss and NR Wray and ZM Zhao and DH Geschwind and PF Sullivan and JW Smoller and PA Holmans and G Breen",

year = "2015",

doi = "10.1038/nn.3922",

language = "Undefined/Unknown",

volume = "18",

pages = "199--209",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "2",

}

O'Dushlaine, C, Rossin, L, Lee, PH, Duncan, L, Parikshak, NN, Newhouse, S, Ripke, S, Neale, BM, Purcell, SM, Posthuma, D, Nurnberger, JI, Lee, SH, Faraone, SV, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayes, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DHR, Bloss, CS, Boehnke, M, Boomsma, DI, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas Sanahuja, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Mattheisen, M, Cloninger, CR, Collier, DA, Cook, EH, Coon, H, Cormand, B, Corvin, A, Coryell, WH, Craig, DW, Craig, IW, Crosbie, J, Cuccaro, ML, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, de Geus, EJ, Degenhardt, F, Djurovic, S, Donohoe, GJ, Doyle, AE, Duan, J, Dudbridge, F, Duketis, E, Ebstein, RP, Edenberg, HJ, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, AE, Ferrier, IN, Flicldnger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, NB, Freitag, CM, Friedl, M, Frisen, L, Gailagher, L, Gejman, PV, Georgieva, L, Gershon, ES, Giegling, I, Gill, M, Gordon, SD, Gordon-Smith, K, Green, EK, Greenwood, TA, Grice, DE, Gross, M, Grozeva, D, Guan, W, Gurling, H, de Haan, L, Haines, JL, Hakonarson, H, Hallmayer, J, Hamilton, SP, Hamshere, ML, Hansen, TF, Hartmann, AM, Hautzinger, M, Heath, AC, Henders, AK, Herms, S, Hickie, IB, Hipolito, M, Hoefels, S, Holsboer, F, Hoogendijk, W, Hottenga, JJ, Hultman, CM, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, EG, Jones, I, Jones, L, Tzeng, JY, Kahler, AK, Kahn, RS, Kandaswamy, R, Keller, MC, Kennedy, JL, Kenny, E, Kent, L, Kim, YJ, Kirov, GK, Klauck, SM, Klei, L, Knowles, JA, Kohli, MA, Koller, DL, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landen, M, Langstrom, N, Lathrop, M, Lawrence, J, Lawson, WB, Leboyer, M, Ledbetter, DH, Lencz, T, Lesch, KP, Levinson, DF, Lewis, CM, Li, J, Lichtenstein, P, Lieberman, JA, Lin, DY, Linszen, DH, Liu, CY, Lohoff, FW, Loo, SK, Lord, C, Lowe, JK, Lucae, S, MacIntyre, DJ, Madden, PAF, Maestrini, E, Magnusson, PKE, Mahon, PB, Maier, W, Malhotra, AK, Mane, SM, Martin, CL, Martin, NG, Matthews, K, Mattingsdal, M, McCarroll, SA, McGhee, KA, McGough, JJ, McGrath, PJ, McGuffin, P, McInnis, MG, McIntosh, A, McKinney, R, McLean, AW, McMahon, FJ, McMahon, WM, McQuillin, A, Medeiros, H, Medland, SE, Meier, S, Melle, I, Meng, F, Meyer, J, Middeldorp, CM, Middleton, L, Milanova, V, Miranda, A, Monaco, AP, Montgomery, GW, Moran, JL, Moreno-De-Luca, D, Morken, G, Morris, DW, Morrow, EM, Moskvina, V, Muglia, P, Muhleisen, TW, Muir, WJ, Muller-Myhsok, B, Murtha, M, Myers, RM, Myin-Germeys, I, Neale, MC, Nelson, SF, Nievergelt, CM, Nikolov, I, Nimgaonkar, V, Nolen, WA, Nothen, MM, Nwulia, EA, Nyholt, DR, Oades, RD, Olincy, A, Oliveira, G, Olsen, L, Ophoff, RA, Osby, U, Owen, MJ, Palotie, A, Parr, JR, Paterson, AD, Pato, CN, Pato, MT, Penninx, BW, Pergadia, ML, Pericak-Vance, MA, Pickard, BS, Pimm, J, Piven, J, Potash, JB, Poustka, F, Propping, P, Puri, V, Quested, DJ, Quinn, EM, Ramos-Quiroga, JA, Rasmussen, HB, Raychaudhuri, S, Rehnstrom, K, Reif, A, Ribases, M, Rice, JP, Rietschel, M, Roeder, K, Roeyers, H, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, AR, Sanders, SJ, Santangelo, SL, Sergeant, JA, Schachar, R, Schalling, M, Schatzberg, AF, Scheftner, WA, Schellenberg, GD, Scherer, SW, Schork, NJ, Schulze, TG, Schumacher, J, Schwarz, M, Scolnick, E, Scott, LJ, Shi, JX, Shilling, PD, Shyn, SI, Silverman, JM, Slager, SL, Smalley, SL, Smit, JH, Smith, EN, Sonuga-Barke, EJS, Cair, DS, State, M, Steffens, M, Steinhausen, HC, Strauss, JS, Strohmaier, J, Stroup, TS, Sutdiffe, JS, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, RC, Todorov, AA, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, EJCG, Van Grootheest, G, van Os, J, Vicente, AM, Vieland, VJ, Vincent, JB, Visscher, PM, Walsh, CA, Wassink, TH, Watson, SJ, Weissman, MM, Werge, T, Wienker, TF, Wijsman, EM, Willemsen, G, Williams, N, Willsey, AJ, Witt, SH, Xu, W, Young, AH, Yu, TW, Zammit, S, Zandi, PP, Zhang, P, Zitman, FG, Zollner, S, Devlin, B, Kelsoe, JR, Sklar, P, Daly, MJ, O'Donovan, MC, Craddock, N, Kendler, KS, Weiss, LA, Wray, NR, Zhao, ZM, Geschwind, DH, Sullivan, PF, Smoller, JW, Holmans, PA & Breen, G 2015, 'Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways', Nature Neuroscience, vol. 18, no. 2, pp. 199-209. https://doi.org/10.1038/nn.3922

TY - JOUR

T1 - Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

AU - O'Dushlaine, C

AU - Rossin, L

AU - Lee, PH

AU - Duncan, L

AU - Parikshak, NN

AU - Newhouse, S

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AU - Breen, G

PY - 2015

Y1 - 2015

N2 - Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

AB - Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

U2 - 10.1038/nn.3922

DO - 10.1038/nn.3922

M3 - Article

SN - 1097-6256

VL - 18

SP - 199

EP - 209

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 2

ER -