Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

SH Lee; S Ripke; BM Neale; SV Faraone; SM Purcell; 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; G Breen; 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; 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; JB Duan; F Dudbridge; E Duketis; RP Ebstein; HJ Edenberg; J Elia; S Ennis; B Etain; A Fanous; AE Farmer; IN Ferrier; M Flickinger; E Fombonne; T Foroud; J Frank; B Franke; C Fraser; R Freedman; NB Freimer; CM Freitag; M Friedl; L Frisen; L Gallagher; PV Gejman; L Georgieva; ES Gershon; DH Geschwind; I Giegling; M Gill; SD Gordon; K Gordon-Smith; EK Green; TA Greenwood; DE Grice; M Gross; D Grozeva; WH Guan; H Gurling; L (Lieuwe) den 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; PA Holmans; 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; Y. 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; PH Lee; 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; M Mattheisen; 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; JI Nurnberger; EA Nwulia; DR Nyholt; C O'Dushlaine; 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; Daniëlle Posthuma; 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; L Rossin; 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; D St Clair; M State; M Steffens; HC Steinhausen; JS Strauss; J Strohmaier; TS Stroup; JS Sutcliffe; 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; PF Sullivan; JW Smoller; KS Kendler; NR Wray

doi:10.1038/ng.2711

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

SH Lee, S Ripke, BM Neale, SV Faraone, SM Purcell, 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 AshersonMH 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, G Breen, 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, 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, JB Duan, F Dudbridge, E Duketis, RP Ebstein, HJ Edenberg, J Elia, S Ennis, B Etain, A Fanous, AE Farmer, IN Ferrier, M Flickinger, E Fombonne, T Foroud, J Frank, B Franke, C Fraser, R Freedman, NB Freimer, CM Freitag, M Friedl, L Frisen, L Gallagher, PV Gejman, L Georgieva, ES Gershon, DH Geschwind, I Giegling, M Gill, SD Gordon, K Gordon-Smith, EK Green, TA Greenwood, DE Grice, M Gross, D Grozeva, WH Guan, H Gurling, L (Lieuwe) den 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, PA Holmans, 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, Y. 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, PH Lee, 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, M Mattheisen, 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, JI Nurnberger, EA Nwulia, DR Nyholt, C O'Dushlaine, 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, Daniëlle Posthuma, 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, L Rossin, 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, D St Clair, M State, M Steffens, HC Steinhausen, JS Strauss, J Strohmaier, TS Stroup, JS Sutcliffe, 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, PF Sullivan, JW Smoller, KS Kendler, NR Wray

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

1648 Citations (Scopus)

Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Original language	Undefined/Unknown
Pages (from-to)	984-994
Number of pages	11
Journal	Nature Genetics
Volume	45
Issue number	9
DOIs	https://doi.org/10.1038/ng.2711
Publication status	Published - 2013

Access to Document

10.1038/ng.2711

http://hdl.handle.net/1765/54262

Cite this

Lee, SH., Ripke, S., Neale, BM., Faraone, SV., Purcell, SM., 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., ... Wray, NR. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45(9), 984-994. https://doi.org/10.1038/ng.2711

@article{ed26e8a781b84d4ba96cffd4e05596d6,

title = "Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs",

abstract = "Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.",

author = "SH Lee and S Ripke and BM Neale and SV Faraone and SM Purcell 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 G Breen 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 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 JB 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 Flickinger 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 Gallagher and PV Gejman and L Georgieva and ES Gershon and DH Geschwind 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 WH Guan and H Gurling and {den Haan}, {L (Lieuwe)} 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 PA Holmans 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 Y. 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 PH Lee and T Lencz and KP Lesch and DF Levinson and CM Lewis and J 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 M Mattheisen 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 JI Nurnberger and EA Nwulia and DR Nyholt and C O'Dushlaine 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 Dani{\"e}lle Posthuma 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 L Rossin 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 {St Clair}, D and M State and M Steffens and HC Steinhausen and JS Strauss and J Strohmaier and TS Stroup and JS Sutcliffe 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 PF Sullivan and JW Smoller and KS Kendler and NR Wray",

year = "2013",

doi = "10.1038/ng.2711",

language = "Undefined/Unknown",

volume = "45",

pages = "984--994",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

Lee, SH, Ripke, S, Neale, BM, Faraone, SV, Purcell, SM, 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, Breen, G, 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, 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, JB, Dudbridge, F, Duketis, E, Ebstein, RP, Edenberg, HJ, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, AE, Ferrier, IN, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, NB, Freitag, CM, Friedl, M, Frisen, L, Gallagher, L, Gejman, PV, Georgieva, L, Gershon, ES, Geschwind, DH, Giegling, I, Gill, M, Gordon, SD, Gordon-Smith, K, Green, EK, Greenwood, TA, Grice, DE, Gross, M, Grozeva, D, Guan, WH, Gurling, H, den 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, Holmans, PA, 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, Y, 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, Lee, PH, 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, Mattheisen, M, 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, Nurnberger, JI, Nwulia, EA, Nyholt, DR, O'Dushlaine, C, 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, Posthuma, D, 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, Rossin, L, 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, St Clair, D, State, M, Steffens, M, Steinhausen, HC, Strauss, JS, Strohmaier, J, Stroup, TS, Sutcliffe, 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, Sullivan, PF, Smoller, JW, Kendler, KS & Wray, NR 2013, 'Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs', Nature Genetics, vol. 45, no. 9, pp. 984-994. https://doi.org/10.1038/ng.2711

TY - JOUR

T1 - Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

AU - Lee, SH

AU - Ripke, S

AU - Neale, BM

AU - Faraone, SV

AU - Purcell, SM

AU - Perlis, RH

AU - Mowry, BJ

AU - Thapar, A

AU - Goddard, ME

AU - Witte, JS

AU - Absher, D

AU - Agartz, I

AU - Akil, H

AU - Amin, F

AU - Andreassen, OA

AU - Anjorin, A

AU - Anney, R

AU - Anttila, V

AU - Arking, DE

AU - Asherson, P

AU - Azevedo, MH

AU - Backlund, L

AU - Badner, JA

AU - Bailey, AJ

AU - Banaschewski, T

AU - Barchas, JD

AU - Barnes, MR

AU - Barrett, TB

AU - Bass, N

AU - Battaglia, A

AU - Bauer, M

AU - Bayes, M

AU - Bellivier, F

AU - Bergen, SE

AU - Berrettini, W

AU - Betancur, C

AU - Bettecken, T

AU - Biederman, J

AU - Binder, EB

AU - Black, DW

AU - Blackwood, DHR

AU - Bloss, CS

AU - Boehnke, M

AU - Boomsma, DI

AU - Breen, G

AU - Breuer, R

AU - Bruggeman, R

AU - Cormican, P

AU - Buccola, NG

AU - Buitelaar, JK

AU - Bunney, WE

AU - Buxbaum, JD

AU - Byerley, WF

AU - Byrne, EM

AU - Caesar, S

AU - Cahn, W

AU - Cantor, RM

AU - Casas Sanahuja, Maria

AU - Chakravarti, A

AU - Chambert, K

AU - Choudhury, K

AU - Cichon, S

AU - Cloninger, CR

AU - Collier, DA

AU - Cook, EH

AU - Coon, H

AU - Cormand, B

AU - Corvin, A

AU - Coryell, WH

AU - Craig, DW

AU - Craig, IW

AU - Crosbie, J

AU - Cuccaro, ML

AU - Curtis, D

AU - Czamara, D

AU - Datta, S

AU - Dawson, G

AU - Day, R

AU - de Geus, EJ

AU - Degenhardt, F

AU - Djurovic, S

AU - Donohoe, GJ

AU - Doyle, AE

AU - Duan, JB

AU - Dudbridge, F

AU - Duketis, E

AU - Ebstein, RP

AU - Edenberg, HJ

AU - Elia, J

AU - Ennis, S

AU - Etain, B

AU - Fanous, A

AU - Farmer, AE

AU - Ferrier, IN

AU - Flickinger, M

AU - Fombonne, E

AU - Foroud, T

AU - Frank, J

AU - Franke, B

AU - Fraser, C

AU - Freedman, R

AU - Freimer, NB

AU - Freitag, CM

AU - Friedl, M

AU - Frisen, L

AU - Gallagher, L

AU - Gejman, PV

AU - Georgieva, L

AU - Gershon, ES

AU - Geschwind, DH

AU - Giegling, I

AU - Gill, M

AU - Gordon, SD

AU - Gordon-Smith, K

AU - Green, EK

AU - Greenwood, TA

AU - Grice, DE

AU - Gross, M

AU - Grozeva, D

AU - Guan, WH

AU - Gurling, H

AU - den Haan, L (Lieuwe)

AU - Haines, JL

AU - Hakonarson, H

AU - Hallmayer, J

AU - Hamilton, SP

AU - Hamshere, ML

AU - Hansen, TF

AU - Hartmann, AM

AU - Hautzinger, M

AU - Heath, AC

AU - Henders, AK

AU - Herms, S

AU - Hickie, IB

AU - Hipolito, M

AU - Hoefels, S

AU - Holmans, PA

AU - Holsboer, F

AU - Hoogendijk, Witte

AU - Hottenga, JJ (Jouke Jan)

AU - Hultman, CM

AU - Hus, V

AU - Ingason, A

AU - Ising, M

AU - Jamain, S

AU - Jones, EG

AU - Jones, I

AU - Jones, L

AU - Tzeng, JY

AU - Kahler, AK

AU - Kahn, RS

AU - Kandaswamy, R

AU - Keller, MC

AU - Kennedy, JL

AU - Kenny, E

AU - Kent, L

AU - Kim, Y.

AU - Kirov, GK

AU - Klauck, SM

AU - Klei, L

AU - Knowles, JA

AU - Kohli, MA

AU - Koller, DL

AU - Konte, B

AU - Korszun, A

AU - Krabbendam, L

AU - Krasucki, R

AU - Kuntsi, J

AU - Kwan, P

AU - Landen, M

AU - Langstrom, N

AU - Lathrop, M

AU - Lawrence, J

AU - Lawson, WB

AU - Leboyer, M

AU - Ledbetter, DH

AU - Lee, PH

AU - Lencz, T

AU - Lesch, KP

AU - Levinson, DF

AU - Lewis, CM

AU - Li, J

AU - Lichtenstein, P

AU - Lieberman, JA

AU - Lin, DY

AU - Linszen, DH

AU - Liu, CY

AU - Lohoff, FW

AU - Loo, SK

AU - Lord, C

AU - Lowe, JK

AU - Lucae, S

AU - MacIntyre, DJ

AU - Madden, PAF

AU - Maestrini, E

AU - Magnusson, PKE

AU - Mahon, PB

AU - Maier, W

AU - Malhotra, AK

AU - Mane, SM

AU - Martin, CL

AU - Martin, NG

AU - Mattheisen, M

AU - Matthews, K

AU - Mattingsdal, M

AU - McCarroll, SA

AU - McGhee, KA

AU - McGough, JJ

AU - McGrath, PJ

AU - McGuffin, P

AU - McInnis, MG

AU - McIntosh, A

AU - McKinney, R

AU - McLean, AW

AU - McMahon, FJ

AU - McMahon, WM

AU - McQuillin, A

AU - Medeiros, H

AU - Medland, SE

AU - Meier, S

AU - Melle, I

AU - Meng, F

AU - Meyer, J

AU - Middeldorp, CM (Christel)

AU - Middleton, L

AU - Milanova, V

AU - Miranda, A

AU - Monaco, AP

AU - Montgomery, GW

AU - Moran, JL

AU - Moreno-De-Luca, D

AU - Morken, G

AU - Morris, DW

AU - Morrow, EM

AU - Moskvina, V

AU - Muglia, P

AU - Muhleisen, TW

AU - Muir, WJ

AU - Muller-Myhsok, B

AU - Murtha, M

AU - Myers, RM

AU - Myin-Germeys, I

AU - Neale, MC

AU - Nelson, SF

AU - Nievergelt, CM

AU - Nikolov, I

AU - Nimgaonkar, V

AU - Nolen, WA

AU - Nothen, MM

AU - Nurnberger, JI

AU - Nwulia, EA

AU - Nyholt, DR

AU - O'Dushlaine, C

AU - Oades, RD

AU - Olincy, A

AU - Oliveira, G

AU - Olsen, L

AU - Ophoff, RA

AU - Osby, U

AU - Owen, MJ

AU - Palotie, A

AU - Parr, JR

AU - Paterson, AD

AU - Pato, CN

AU - Pato, MT

AU - Penninx, BW

AU - Pergadia, ML

AU - Pericak-Vance, MA

AU - Pickard, BS

AU - Pimm, J

AU - Piven, J

AU - Posthuma, Daniëlle

AU - Potash, JB

AU - Poustka, F

AU - Propping, P

AU - Puri, V

AU - Quested, DJ

AU - Quinn, EM

AU - Ramos-Quiroga, JA

AU - Rasmussen, HB

AU - Raychaudhuri, S

AU - Rehnstrom, K

AU - Reif, A

AU - Ribases, M

AU - Rice, JP

AU - Rietschel, M

AU - Roeder, K

AU - Roeyers, H

AU - Rossin, L

AU - Rothenberger, A

AU - Rouleau, G

AU - Ruderfer, D

AU - Rujescu, D

AU - Sanders, AR

AU - Sanders, SJ

AU - Santangelo, SL

AU - Sergeant, JA

AU - Schachar, R

AU - Schalling, M

AU - Schatzberg, AF

AU - Scheftner, WA

AU - Schellenberg, GD

AU - Scherer, SW

AU - Schork, NJ

AU - Schulze, TG

AU - Schumacher, J

AU - Schwarz, M

AU - Scolnick, E

AU - Scott, LJ

AU - Shi, JX

AU - Shilling, PD

AU - Shyn, SI

AU - Silverman, JM

AU - Slager, SL

AU - Smalley, SL

AU - Smit, JH

AU - Smith, EN

AU - Sonuga-Barke, EJS

AU - St Clair, D

AU - State, M

AU - Steffens, M

AU - Steinhausen, HC

AU - Strauss, JS

AU - Strohmaier, J

AU - Stroup, TS

AU - Sutcliffe, JS

AU - Szatmari, P

AU - Szelinger, S

AU - Thirumalai, S

AU - Thompson, RC

AU - Todorov, AA

AU - Tozzi, F

AU - Treutlein, J

AU - Uhr, M

AU - van den Oord, EJCG (Edwin)

AU - Van Grootheest, G

AU - van Os, J

AU - Vicente, AM

AU - Vieland, VJ

AU - Vincent, JB

AU - Visscher, PM

AU - Walsh, CA

AU - Wassink, TH

AU - Watson, SJ

AU - Weissman, MM

AU - Werge, T

AU - Wienker, TF

AU - Wijsman, EM

AU - Willemsen, G

AU - Williams, N

AU - Willsey, AJ

AU - Witt, SH

AU - Xu, W

AU - Young, AH

AU - Yu, TW

AU - Zammit, S

AU - Zandi, PP

AU - Zhang, P (Ping)

AU - Zitman, FG

AU - Zollner, S

AU - Devlin, B

AU - Kelsoe, JR

AU - Sklar, P

AU - Daly, MJ

AU - O'Donovan, MC

AU - Craddock, N

AU - Sullivan, PF

AU - Smoller, JW

AU - Kendler, KS

AU - Wray, NR

PY - 2013

Y1 - 2013

N2 - Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

AB - Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

U2 - 10.1038/ng.2711

DO - 10.1038/ng.2711

M3 - Article

SN - 1061-4036

VL - 45

SP - 984

EP - 994

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -