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

(2015) NATURE NEUROSCIENCE. 18(2). p.199-209
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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.
Keywords
DE-NOVO MUTATIONS, SCHIZOPHRENIA, METHYLATION, LOCI, BURDEN, PROMOTERS, BRAIN, DISORDERS, AUTISM

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MLA
O’Dushlaine, C et al. “Psychiatric Genome-wide Association Study Analyses Implicate Neuronal, Immune and Histone Pathways.” NATURE NEUROSCIENCE 18.2 (2015): 199–209. Print.
APA
O’Dushlaine, C., Rossin, L., Lee, P., Duncan, L., Parikshak, N., Newhouse, S., Ripke, S., et al. (2015). Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. NATURE NEUROSCIENCE, 18(2), 199–209.
Chicago author-date
O’Dushlaine, C, L Rossin, PH Lee, L Duncan, NN Parikshak, S Newhouse, S Ripke, et al. 2015. “Psychiatric Genome-wide Association Study Analyses Implicate Neuronal, Immune and Histone Pathways.” Nature Neuroscience 18 (2): 199–209.
Chicago author-date (all authors)
O’Dushlaine, C, L Rossin, PH Lee, L Duncan, NN Parikshak, S Newhouse, S Ripke, BM Neale, SM Purcell, D 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, M Casas, 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, WJ Hoogendijk, JJ 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, J 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 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, Herbert 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, Edmund 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 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 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, and G Breen. 2015. “Psychiatric Genome-wide Association Study Analyses Implicate Neuronal, Immune and Histone Pathways.” Nature Neuroscience 18 (2): 199–209.
Vancouver
1.
O’Dushlaine C, Rossin L, Lee P, Duncan L, Parikshak N, Newhouse S, et al. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. NATURE NEUROSCIENCE. NEW YORK: NATURE PUBLISHING GROUP; 2015;18(2):199–209.
IEEE
[1]
C. O’Dushlaine et al., “Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways,” NATURE NEUROSCIENCE, vol. 18, no. 2, pp. 199–209, 2015.
@article{7255083,
  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       = {O'Dushlaine, C and Rossin, L and Lee, PH and Duncan, L and Parikshak, NN and Newhouse, S and Ripke, S and Neale, BM and Purcell, SM and Posthuma, D and Nurnberger, JI and Lee, SH and Faraone, SV and Perlis, RH and Mowry, BJ and Thapar, A and Goddard, ME and Witte, JS and Absher, D and Agartz, I and Akil, H and Amin, F and Andreassen, OA and Anjorin, A and Anney, R and Anttila, V and Arking, DE and Asherson, P and Azevedo, MH and Backlund, L and Badner, JA and Bailey, AJ and Banaschewski, T and Barchas, JD and Barnes, MR and Barrett, TB and Bass, N and Battaglia, A and Bauer, M and Bayes, M and Bellivier, F and Bergen, SE and Berrettini, W and Betancur, C and Bettecken, T and Biederman, J and Binder, EB and Black, DW and Blackwood, DHR and Bloss, CS and Boehnke, M and Boomsma, DI and Breuer, R and Bruggeman, R and Cormican, P and Buccola, NG and Buitelaar, JK and Bunney, WE and Buxbaum, JD and Byerley, WF and Byrne, EM and Caesar, S and Cahn, W and Cantor, RM and Casas, M and Chakravarti, A and Chambert, K and Choudhury, K and Cichon, S and Mattheisen, M and Cloninger, CR and Collier, DA and Cook, EH and Coon, H and Cormand, B and Corvin, A and Coryell, WH and Craig, DW and Craig, IW and Crosbie, J and Cuccaro, ML and Curtis, D and Czamara, D and Datta, S and Dawson, G and Day, R and De Geus, EJ and Degenhardt, F and Djurovic, S and Donohoe, GJ and Doyle, AE and Duan, J and Dudbridge, F and Duketis, E and Ebstein, RP and Edenberg, HJ and Elia, J and Ennis, S and Etain, B and Fanous, A and Farmer, AE and Ferrier, IN and Flicldnger, M and Fombonne, E and Foroud, T and Frank, J and Franke, B and Fraser, C and Freedman, R and Freimer, NB and Freitag, CM and Friedl, M and Frisen, L and Gailagher, L and Gejman, PV and Georgieva, L and Gershon, ES and Giegling, I and Gill, M and Gordon, SD and Gordon-Smith, K and Green, EK and Greenwood, TA and Grice, DE and Gross, M and Grozeva, D and Guan, W and Gurling, H and De Haan, L and Haines, JL and Hakonarson, H and Hallmayer, J and Hamilton, SP and Hamshere, ML and Hansen, TF and Hartmann, AM and Hautzinger, M and Heath, AC and Henders, AK and Herms, S and Hickie, IB and Hipolito, M and Hoefels, S and Holsboer, F and Hoogendijk, WJ and Hottenga, JJ and Hultman, CM and Hus, V and Ingason, A and Ising, M and Jamain, S and Jones, EG and Jones, I and Jones, L and Tzeng, JY and Kahler, AK and Kahn, RS and Kandaswamy, R and Keller, MC and Kennedy, JL and Kenny, E and Kent, L and Kim, YJ and Kirov, GK and Klauck, SM and Klei, L and Knowles, JA and Kohli, MA and Koller, DL and Konte, B and Korszun, A and Krabbendam, L and Krasucki, R and Kuntsi, J and Kwan, P and Landen, M and Langstrom, N and Lathrop, M and Lawrence, J and Lawson, WB and Leboyer, M and Ledbetter, DH and Lencz, T and Lesch, KP and Levinson, DF and Lewis, CM and Li, J and Lichtenstein, P and Lieberman, JA and Lin, DY and Linszen, DH and Liu, CY and Lohoff, FW and Loo, SK and Lord, C and Lowe, JK and Lucae, S and MacIntyre, DJ and Madden, PAF and Maestrini, E and Magnusson, PKE and Mahon, PB and Maier, W and Malhotra, AK and Mane, SM and Martin, CL and Martin, NG and Matthews, K and Mattingsdal, M and McCarroll, SA and McGhee, KA and McGough, JJ and McGrath, PJ and McGuffin, P and McInnis, MG and McIntosh, A and McKinney, R and McLean, AW and McMahon, FJ and McMahon, WM and McQuillin, A and Medeiros, H and Medland, SE and Meier, S and Melle, I and Meng, F and Meyer, J and Middeldorp, CM and Middleton, L and Milanova, V and Miranda, A and Monaco, AP and Montgomery, GW and Moran, JL and Moreno-De-Luca, D and Morken, G and Morris, DW and Morrow, EM and Moskvina, V and Muglia, P and Muhleisen, TW and Muir, WJ and Muller-Myhsok, B and Murtha, M and Myers, RM and Myin-Germeys, I and Neale, MC and Nelson, SF and Nievergelt, CM and Nikolov, I and Nimgaonkar, V and Nolen, WA and Nothen, MM and Nwulia, EA and Nyholt, DR and Oades, RD and Olincy, A and Oliveira, G and Olsen, L and Ophoff, RA and Osby, U and Owen, MJ and Palotie, A and Parr, JR and Paterson, AD and Pato, CN and Pato, MT and Penninx, BW and Pergadia, ML and Pericak-Vance, MA and Pickard, BS and Pimm, J and Piven, J and Potash, JB and Poustka, F and Propping, P and Puri, V and Quested, DJ and Quinn, EM and Ramos-Quiroga, JA and Rasmussen, HB and Raychaudhuri, S and Rehnstrom, K and Reif, A and Ribases, M and Rice, JP and Rietschel, M and Roeder, K and Roeyers, Herbert and Rothenberger, A and Rouleau, G and Ruderfer, D and Rujescu, D and Sanders, AR and Sanders, SJ and Santangelo, SL and Sergeant, JA and Schachar, R and Schalling, M and Schatzberg, AF and Scheftner, WA and Schellenberg, GD and Scherer, SW and Schork, NJ and Schulze, TG and Schumacher, J and Schwarz, M and Scolnick, E and Scott, LJ and Shi, JX and Shilling, PD and Shyn, SI and Silverman, JM and Slager, SL and Smalley, SL and Smit, JH and Smith, EN and Barke, Edmund and Cair, DS and State, M and Steffens, M and Steinhausen, HC and Strauss, JS and Strohmaier, J and Stroup, TS and Sutdiffe, JS and Szatmari, P and Szelinger, S and Thirumalai, S and Thompson, RC and Todorov, AA and Tozzi, F and Treutlein, J and Uhr, M and Van den Oord, EJCG and Van Grootheest, G and Van Os, J and Vicente, AM and Vieland, VJ and Vincent, JB and Visscher, PM and Walsh, CA and Wassink, TH and Watson, SJ and Weissman, MM and Werge, T and Wienker, TF and Wijsman, EM and Willemsen, G and Williams, N and Willsey, AJ and Witt, SH and Xu, W and Young, AH and Yu, TW and Zammit, S and Zandi, PP and Zhang, P and Zitman, FG and Zollner, S and Devlin, B and Kelsoe, JR and Sklar, P and Daly, MJ and O'Donovan, MC and Craddock, N and Kendler, KS and Weiss, LA and Wray, NR and Zhao, ZM and Geschwind, DH and Sullivan, PF and Smoller, JW and Holmans, PA and Breen, G},
  issn         = {1097-6256},
  journal      = {NATURE NEUROSCIENCE},
  keywords     = {DE-NOVO MUTATIONS,SCHIZOPHRENIA,METHYLATION,LOCI,BURDEN,PROMOTERS,BRAIN,DISORDERS,AUTISM},
  language     = {eng},
  number       = {2},
  pages        = {199--209},
  publisher    = {NATURE PUBLISHING GROUP},
  title        = {Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways},
  url          = {http://dx.doi.org/10.1038/nn.3922},
  volume       = {18},
  year         = {2015},
}

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