The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects

W. J. Peyrot, S. H. Lee, Y. Milaneschi, A. Abdellaoui, E. M. Byrne, T. Esko, E. J C De Geus, G. Hemani, J. J. Hottenga, S. Kloiber, D. F. Levinson, S. Lucae, N. G. Martin, S. E. Medland, A. Metspalu, L. Milani, M. M. Noethen, J. B. Potash, M. Rietschel, C. A. RietveldS. Ripke, J. Shi, G. Willemsen, Z. Zhu, D. I. Boomsma, N. R. Wray, B. W J H Penninx, C. M. Lewis, S. P. Hamilton, M. M. Weissman, G. Breen, D. H. Blackwood, S. Cichon, A. C. Heath, F. Holsboer, P. A. Madden, P. McGuffin, P. Muglia, M. L. Pergadia, D. Lin, B. Müller-Myhsok, S. Steinberg, H. J. Grabe, P. Lichtenstein, P. Magnusson, R. H. Perlis, M. Preisig, J. W. Smoller, K. Stefansson, R. Uher, Z. Kutalik, K. E. Tansey, A. Teumer, A. Viktorin, M. R. Barnes, T. Bettecken, E. B. Binder, R. Breuer, V. M. Castro, S. E. Churchill, W. H. Coryell, N. Craddock, I. W. Craig, D. Czamara, F. Degenhardt, A. E. Farmer, M. Fava, J. Frank, V. S. Gainer, P. J. Gallagher, S. D. Gordon, S. Goryachev, M. Gross, M. Guipponi, A. K. Henders, S. Herms, I. B. Hickie, S. Hoefels, W. Hoogendijk, D. V. Iosifescu, M. Ising, I. Jones, L. Jones, T. Jung-Ying, J. A. Knowles, I. S. Kohane, M. A. Kohli, A. Korszun, M. Landen, W. B. Lawson, G. Lewis, D. Macintyre, W. Maier, M. Mattheisen, P. J. McGrath, A. McIntosh, A. McLean, C. M. Middeldorp, L. Middleton, G. M. Montgomery, S. N. Murphy, M. Nauck, W. A. Nolen, D. R. Nyholt, M. O'Donovan, H. Oskarsson, N. Pedersen, W. A. Scheftner, A. Schulz, T. G. Schulze, S. I. Shyn, E. Sigurdsson, S. L. Slager, J. H. Smit, H. Stefansson, M. Steffens, T. Thorgeirsson, F. Tozzi, J. Treutlein, M. Uhr, E. J. Van Den Oord, G. Van Grootheest, H. Völzke, J. B. Weilburg, G. Willemsen, F. G. Zitman, B. Neale, M. Daly, P. F. Sullivan, Arpana Agrawal, Eva Albrecht, Behrooz Z Alizadeh, Jüri Allik, Najaf Amin, John R. Attia, Stefania Bandinelli, John Barnard, Franois Bastardot, Sebastian E Baumeister, Jonathan Beauchamp, Daniel J. Benjamin, Kelly S. Benke, David A. Bennett, Klaus Berger, Lawrence F. Bielak, Laura J. Bierut, Jeffrey A. Boatman, Patricia A. Boyle, Ute Bültmann, Harry Campbell, David Cesarini, Christopher F. Chabris, Lynn Cherkas, Mina K. Chung, Dalton Conley, Francesco Cucca, George Davey-Smith, Gail Davies, Mariza De Andrade, Philip L. De Jager, Christiaan De Leeuw, Jan Emmanuel De Neve, Ian J. Deary, George V. Dedoussis, Panos Deloukas, Jaime Derringer, Maria Dimitriou, Gudny Eiriksdottir, Niina Eklund, Martin F. Elderson, Johan G. Eriksson, Daniel S. Evans, David M. Evans, Jessica D. Faul, Rudolf Fehrmann, Luigi Ferrucci, Krista Fischer, Lude Franke, Melissa E. Garcia, Christian Gieger, Hkon K. Gjessing, Patrick J F Groenen, Henrik Grönberg, Vilmundur Gudnason, Sara Hägg, Per Hall, Jennifer R. Harris, Juliette M. Harris, Tamara B. Harris, Nicholas D. Hastie, Caroline Hayward, Andrew C. Heath, Dena G. Hernandez, Wolgang Hoffmann, Adriaan Hofman, Albert Hofman, Rolf Holle, Elizabeth G. Holliday, Christina Holzapfel, William G. Iacono, Carla A. Ibrahim-Verbaas, Thomas Illig, Erik Ingelsson, Bo Jacobsson, Marjo Riitta Järvelin, Min A. Jhun, Magnus Johannesson, Peter K. Joshi, Astanand Jugessur, Marika Kaakinen, Mika Kähönen, Stavroula Kanoni, Jaakkko Kaprio, Sharon L R Kardia, Juha Karjalainen, Robert M. Kirkpatrick, Philipp D. Koellinger, Ivana Kolcic, Matthew Kowgier, Kati Kristiansson, Robert F. Krueger, Zóltan Kutalik, Jari Lahti, David Laibson, Antti Latvala, Lenore J. Launer, Debbie A. Lawlor, Terho Lethimäki, Jingmei Li, Paul Lichtenstein, Peter K. Lichtner, David C. Liewald, Peng Lin, Penelope A. Lind, Yongmei Liu, Kurt Lohman, Marisa Loitfelder, Pamela A. Madden, Patrick K E Magnusson, Tomi E. Mäkinen, Pedro Marques Vidal, Nicolas W. Martin, Marco Masala, Matt McGue, George McMahon, Osorio Meirelles, Michelle N. Meyer, Andreas Mielck, Lili Milani, Michael B. Miller, Grant W. Montgomery, Sutapa Mukherjee, Ronny Myhre, Marja Liisa Nuotio, Dale R. Nyholt, Christopher J Oldmeadow, Ben A. Oostra, Lyle J. Palmer, Aarno Palotie, Markus Perola, Katja E. Petrovic, Patricia A. Peyser, Ozren Polašek, Danielle Posthuma, Martin Preisig, Lydia Quaye, Katri Räikkönen, Olli T. Raitakari, Anu Realo, Eva Reinmaa, John P. Rice, Susan M. Ring, Samuli Ripatti, Fernando Rivadeneira, Thais S. Rizzi, Igor Rudan, Aldo Rustichini, Veikko Salomaa, Antti Pekka Sarin, David Schlessinger, Helena Schmidt, Reinhold Schmidt, Rodney J. Scott, Konstantin Shakhbazov, Albert V. Smith, Jennifer A. Smith, Harold Snieder, Beate St Pourcain, John M. Starr, Jae Hoon Sul, Ida Surakka, Rauli Svento, Toshiko Tanaka, Antonio Terracciano, Alexander Teumer, A. Roy Thurik, Henning Tiemeier, Nicholas J. Timpson, André G. Uitterlinden, Matthijs J H M Van Der Loos, Cornelia M. Van Duijn, Frank J A Van Rooij, David R. Van Wagoner, Erkki Vartiainen, Jorma Viikari, Peter M. Visscher, Veronique Vitart, Peter K. Vollenweider, Henry Völzke, Judith M. Vonk, Gérard Waeber, David R. Weir, Jürgen Wellmann, Harm Jan Westra, H. Erich Wichmann, Elisabeth Widen, James F. Wilson, Alan F. Wright, Jian Yang, Lei Yu, Wei Zhao

    Research output: Contribution to journalArticle

    Abstract

    An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

    Original languageEnglish (US)
    Pages (from-to)735-743
    Number of pages9
    JournalMolecular Psychiatry
    Volume20
    Issue number6
    DOIs
    StatePublished - Jun 26 2015

    Fingerprint

    Major Depressive Disorder
    Depression
    Single Nucleotide Polymorphism
    Genomics
    Mental Disorders
    Social Class
    Meta-Analysis
    Logistic Models
    Odds Ratio

    ASJC Scopus subject areas

    • Molecular Biology
    • Cellular and Molecular Neuroscience
    • Psychiatry and Mental health

    Cite this

    Peyrot, W. J., Lee, S. H., Milaneschi, Y., Abdellaoui, A., Byrne, E. M., Esko, T., ... Zhao, W. (2015). The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects. Molecular Psychiatry, 20(6), 735-743. https://doi.org/10.1038/mp.2015.50

    The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects. / Peyrot, W. J.; Lee, S. H.; Milaneschi, Y.; Abdellaoui, A.; Byrne, E. M.; Esko, T.; De Geus, E. J C; Hemani, G.; Hottenga, J. J.; Kloiber, S.; Levinson, D. F.; Lucae, S.; Martin, N. G.; Medland, S. E.; Metspalu, A.; Milani, L.; Noethen, M. M.; Potash, J. B.; Rietschel, M.; Rietveld, C. A.; Ripke, S.; Shi, J.; Willemsen, G.; Zhu, Z.; Boomsma, D. I.; Wray, N. R.; Penninx, B. W J H; Lewis, C. M.; Hamilton, S. P.; Weissman, M. M.; Breen, G.; Blackwood, D. H.; Cichon, S.; Heath, A. C.; Holsboer, F.; Madden, P. A.; McGuffin, P.; Muglia, P.; Pergadia, M. L.; Lin, D.; Müller-Myhsok, B.; Steinberg, S.; Grabe, H. J.; Lichtenstein, P.; Magnusson, P.; Perlis, R. H.; Preisig, M.; Smoller, J. W.; Stefansson, K.; Uher, R.; Kutalik, Z.; Tansey, K. E.; Teumer, A.; Viktorin, A.; Barnes, M. R.; Bettecken, T.; Binder, E. B.; Breuer, R.; Castro, V. M.; Churchill, S. E.; Coryell, W. H.; Craddock, N.; Craig, I. W.; Czamara, D.; Degenhardt, F.; Farmer, A. E.; Fava, M.; Frank, J.; Gainer, V. S.; Gallagher, P. J.; Gordon, S. D.; Goryachev, S.; Gross, M.; Guipponi, M.; Henders, A. K.; Herms, S.; Hickie, I. B.; Hoefels, S.; Hoogendijk, W.; Iosifescu, D. V.; Ising, M.; Jones, I.; Jones, L.; Jung-Ying, T.; Knowles, J. A.; Kohane, I. S.; Kohli, M. A.; Korszun, A.; Landen, M.; Lawson, W. B.; Lewis, G.; Macintyre, D.; Maier, W.; Mattheisen, M.; McGrath, P. J.; McIntosh, A.; McLean, A.; Middeldorp, C. M.; Middleton, L.; Montgomery, G. M.; Murphy, S. N.; Nauck, M.; Nolen, W. A.; Nyholt, D. R.; O'Donovan, M.; Oskarsson, H.; Pedersen, N.; Scheftner, W. A.; Schulz, A.; Schulze, T. G.; Shyn, S. I.; Sigurdsson, E.; Slager, S. L.; Smit, J. H.; Stefansson, H.; Steffens, M.; Thorgeirsson, T.; Tozzi, F.; Treutlein, J.; Uhr, M.; Van Den Oord, E. J.; Van Grootheest, G.; Völzke, H.; Weilburg, J. B.; Willemsen, G.; Zitman, F. G.; Neale, B.; Daly, M.; Sullivan, P. F.; Agrawal, Arpana; Albrecht, Eva; Z Alizadeh, Behrooz; Allik, Jüri; Amin, Najaf; Attia, John R.; Bandinelli, Stefania; Barnard, John; Bastardot, Franois; E Baumeister, Sebastian; Beauchamp, Jonathan; Benjamin, Daniel J.; Benke, Kelly S.; Bennett, David A.; Berger, Klaus; Bielak, Lawrence F.; Bierut, Laura J.; Boatman, Jeffrey A.; Boyle, Patricia A.; Bültmann, Ute; Campbell, Harry; Cesarini, David; Chabris, Christopher F.; Cherkas, Lynn; Chung, Mina K.; Conley, Dalton; Cucca, Francesco; Davey-Smith, George; Davies, Gail; De Andrade, Mariza; De Jager, Philip L.; De Leeuw, Christiaan; De Neve, Jan Emmanuel; Deary, Ian J.; Dedoussis, George V.; Deloukas, Panos; Derringer, Jaime; Dimitriou, Maria; Eiriksdottir, Gudny; Eklund, Niina; Elderson, Martin F.; Eriksson, Johan G.; Evans, Daniel S.; Evans, David M.; Faul, Jessica D.; Fehrmann, Rudolf; Ferrucci, Luigi; Fischer, Krista; Franke, Lude; Garcia, Melissa E.; Gieger, Christian; Gjessing, Hkon K.; Groenen, Patrick J F; Grönberg, Henrik; Gudnason, Vilmundur; Hägg, Sara; Hall, Per; Harris, Jennifer R.; Harris, Juliette M.; Harris, Tamara B.; Hastie, Nicholas D.; Hayward, Caroline; Heath, Andrew C.; Hernandez, Dena G.; Hoffmann, Wolgang; Hofman, Adriaan; Hofman, Albert; Holle, Rolf; Holliday, Elizabeth G.; Holzapfel, Christina; Iacono, William G.; Ibrahim-Verbaas, Carla A.; Illig, Thomas; Ingelsson, Erik; Jacobsson, Bo; Järvelin, Marjo Riitta; Jhun, Min A.; Johannesson, Magnus; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Kaprio, Jaakkko; Kardia, Sharon L R; Karjalainen, Juha; Kirkpatrick, Robert M.; Koellinger, Philipp D.; Kolcic, Ivana; Kowgier, Matthew; Kristiansson, Kati; Krueger, Robert F.; Kutalik, Zóltan; Lahti, Jari; Laibson, David; Latvala, Antti; Launer, Lenore J.; Lawlor, Debbie A.; Lethimäki, Terho; Li, Jingmei; Lichtenstein, Paul; Lichtner, Peter K.; Liewald, David C.; Lin, Peng; Lind, Penelope A.; Liu, Yongmei; Lohman, Kurt; Loitfelder, Marisa; Madden, Pamela A.; Magnusson, Patrick K E; Mäkinen, Tomi E.; Vidal, Pedro Marques; Martin, Nicolas W.; Masala, Marco; McGue, Matt; McMahon, George; Meirelles, Osorio; Meyer, Michelle N.; Mielck, Andreas; Milani, Lili; Miller, Michael B.; Montgomery, Grant W.; Mukherjee, Sutapa; Myhre, Ronny; Nuotio, Marja Liisa; Nyholt, Dale R.; J Oldmeadow, Christopher; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Perola, Markus; Petrovic, Katja E.; Peyser, Patricia A.; Polašek, Ozren; Posthuma, Danielle; Preisig, Martin; Quaye, Lydia; Räikkönen, Katri; Raitakari, Olli T.; Realo, Anu; Reinmaa, Eva; Rice, John P.; Ring, Susan M.; Ripatti, Samuli; Rivadeneira, Fernando; Rizzi, Thais S.; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sarin, Antti Pekka; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Shakhbazov, Konstantin; Smith, Albert V.; Smith, Jennifer A.; Snieder, Harold; St Pourcain, Beate; Starr, John M.; Sul, Jae Hoon; Surakka, Ida; Svento, Rauli; Tanaka, Toshiko; Terracciano, Antonio; Teumer, Alexander; Thurik, A. Roy; Tiemeier, Henning; Timpson, Nicholas J.; Uitterlinden, André G.; Van Der Loos, Matthijs J H M; Van Duijn, Cornelia M.; Van Rooij, Frank J A; Van Wagoner, David R.; Vartiainen, Erkki; Viikari, Jorma; Visscher, Peter M.; Vitart, Veronique; Vollenweider, Peter K.; Völzke, Henry; Vonk, Judith M.; Waeber, Gérard; Weir, David R.; Wellmann, Jürgen; Westra, Harm Jan; Wichmann, H. Erich; Widen, Elisabeth; Wilson, James F.; Wright, Alan F.; Yang, Jian; Yu, Lei; Zhao, Wei.

    In: Molecular Psychiatry, Vol. 20, No. 6, 26.06.2015, p. 735-743.

    Research output: Contribution to journalArticle

    Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Byrne, EM, Esko, T, De Geus, EJC, Hemani, G, Hottenga, JJ, Kloiber, S, Levinson, DF, Lucae, S, Martin, NG, Medland, SE, Metspalu, A, Milani, L, Noethen, MM, Potash, JB, Rietschel, M, Rietveld, CA, Ripke, S, Shi, J, Willemsen, G, Zhu, Z, Boomsma, DI, Wray, NR, Penninx, BWJH, Lewis, CM, Hamilton, SP, Weissman, MM, Breen, G, Blackwood, DH, Cichon, S, Heath, AC, Holsboer, F, Madden, PA, McGuffin, P, Muglia, P, Pergadia, ML, Lin, D, Müller-Myhsok, B, Steinberg, S, Grabe, HJ, Lichtenstein, P, Magnusson, P, Perlis, RH, Preisig, M, Smoller, JW, Stefansson, K, Uher, R, Kutalik, Z, Tansey, KE, Teumer, A, Viktorin, A, Barnes, MR, Bettecken, T, Binder, EB, Breuer, R, Castro, VM, Churchill, SE, Coryell, WH, Craddock, N, Craig, IW, Czamara, D, Degenhardt, F, Farmer, AE, Fava, M, Frank, J, Gainer, VS, Gallagher, PJ, Gordon, SD, Goryachev, S, Gross, M, Guipponi, M, Henders, AK, Herms, S, Hickie, IB, Hoefels, S, Hoogendijk, W, Iosifescu, DV, Ising, M, Jones, I, Jones, L, Jung-Ying, T, Knowles, JA, Kohane, IS, Kohli, MA, Korszun, A, Landen, M, Lawson, WB, Lewis, G, Macintyre, D, Maier, W, Mattheisen, M, McGrath, PJ, McIntosh, A, McLean, A, Middeldorp, CM, Middleton, L, Montgomery, GM, Murphy, SN, Nauck, M, Nolen, WA, Nyholt, DR, O'Donovan, M, Oskarsson, H, Pedersen, N, Scheftner, WA, Schulz, A, Schulze, TG, Shyn, SI, Sigurdsson, E, Slager, SL, Smit, JH, Stefansson, H, Steffens, M, Thorgeirsson, T, Tozzi, F, Treutlein, J, Uhr, M, Van Den Oord, EJ, Van Grootheest, G, Völzke, H, Weilburg, JB, Willemsen, G, Zitman, FG, Neale, B, Daly, M, Sullivan, PF, Agrawal, A, Albrecht, E, Z Alizadeh, B, Allik, J, Amin, N, Attia, JR, Bandinelli, S, Barnard, J, Bastardot, F, E Baumeister, S, Beauchamp, J, Benjamin, DJ, Benke, KS, Bennett, DA, Berger, K, Bielak, LF, Bierut, LJ, Boatman, JA, Boyle, PA, Bültmann, U, Campbell, H, Cesarini, D, Chabris, CF, Cherkas, L, Chung, MK, Conley, D, Cucca, F, Davey-Smith, G, Davies, G, De Andrade, M, De Jager, PL, De Leeuw, C, De Neve, JE, Deary, IJ, Dedoussis, GV, Deloukas, P, Derringer, J, Dimitriou, M, Eiriksdottir, G, Eklund, N, Elderson, MF, Eriksson, JG, Evans, DS, Evans, DM, Faul, JD, Fehrmann, R, Ferrucci, L, Fischer, K, Franke, L, Garcia, ME, Gieger, C, Gjessing, HK, Groenen, PJF, Grönberg, H, Gudnason, V, Hägg, S, Hall, P, Harris, JR, Harris, JM, Harris, TB, Hastie, ND, Hayward, C, Heath, AC, Hernandez, DG, Hoffmann, W, Hofman, A, Hofman, A, Holle, R, Holliday, EG, Holzapfel, C, Iacono, WG, Ibrahim-Verbaas, CA, Illig, T, Ingelsson, E, Jacobsson, B, Järvelin, MR, Jhun, MA, Johannesson, M, Joshi, PK, Jugessur, A, Kaakinen, M, Kähönen, M, Kanoni, S, Kaprio, J, Kardia, SLR, Karjalainen, J, Kirkpatrick, RM, Koellinger, PD, Kolcic, I, Kowgier, M, Kristiansson, K, Krueger, RF, Kutalik, Z, Lahti, J, Laibson, D, Latvala, A, Launer, LJ, Lawlor, DA, Lethimäki, T, Li, J, Lichtenstein, P, Lichtner, PK, Liewald, DC, Lin, P, Lind, PA, Liu, Y, Lohman, K, Loitfelder, M, Madden, PA, Magnusson, PKE, Mäkinen, TE, Vidal, PM, Martin, NW, Masala, M, McGue, M, McMahon, G, Meirelles, O, Meyer, MN, Mielck, A, Milani, L, Miller, MB, Montgomery, GW, Mukherjee, S, Myhre, R, Nuotio, ML, Nyholt, DR, J Oldmeadow, C, Oostra, BA, Palmer, LJ, Palotie, A, Perola, M, Petrovic, KE, Peyser, PA, Polašek, O, Posthuma, D, Preisig, M, Quaye, L, Räikkönen, K, Raitakari, OT, Realo, A, Reinmaa, E, Rice, JP, Ring, SM, Ripatti, S, Rivadeneira, F, Rizzi, TS, Rudan, I, Rustichini, A, Salomaa, V, Sarin, AP, Schlessinger, D, Schmidt, H, Schmidt, R, Scott, RJ, Shakhbazov, K, Smith, AV, Smith, JA, Snieder, H, St Pourcain, B, Starr, JM, Sul, JH, Surakka, I, Svento, R, Tanaka, T, Terracciano, A, Teumer, A, Thurik, AR, Tiemeier, H, Timpson, NJ, Uitterlinden, AG, Van Der Loos, MJHM, Van Duijn, CM, Van Rooij, FJA, Van Wagoner, DR, Vartiainen, E, Viikari, J, Visscher, PM, Vitart, V, Vollenweider, PK, Völzke, H, Vonk, JM, Waeber, G, Weir, DR, Wellmann, J, Westra, HJ, Wichmann, HE, Widen, E, Wilson, JF, Wright, AF, Yang, J, Yu, L & Zhao, W 2015, 'The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects', Molecular Psychiatry, vol. 20, no. 6, pp. 735-743. https://doi.org/10.1038/mp.2015.50
    Peyrot, W. J. ; Lee, S. H. ; Milaneschi, Y. ; Abdellaoui, A. ; Byrne, E. M. ; Esko, T. ; De Geus, E. J C ; Hemani, G. ; Hottenga, J. J. ; Kloiber, S. ; Levinson, D. F. ; Lucae, S. ; Martin, N. G. ; Medland, S. E. ; Metspalu, A. ; Milani, L. ; Noethen, M. M. ; Potash, J. B. ; Rietschel, M. ; Rietveld, C. A. ; Ripke, S. ; Shi, J. ; Willemsen, G. ; Zhu, Z. ; Boomsma, D. I. ; Wray, N. R. ; Penninx, B. W J H ; Lewis, C. M. ; Hamilton, S. P. ; Weissman, M. M. ; Breen, G. ; Blackwood, D. H. ; Cichon, S. ; Heath, A. C. ; Holsboer, F. ; Madden, P. A. ; McGuffin, P. ; Muglia, P. ; Pergadia, M. L. ; Lin, D. ; Müller-Myhsok, B. ; Steinberg, S. ; Grabe, H. J. ; Lichtenstein, P. ; Magnusson, P. ; Perlis, R. H. ; Preisig, M. ; Smoller, J. W. ; Stefansson, K. ; Uher, R. ; Kutalik, Z. ; Tansey, K. E. ; Teumer, A. ; Viktorin, A. ; Barnes, M. R. ; Bettecken, T. ; Binder, E. B. ; Breuer, R. ; Castro, V. M. ; Churchill, S. E. ; Coryell, W. H. ; Craddock, N. ; Craig, I. W. ; Czamara, D. ; Degenhardt, F. ; Farmer, A. E. ; Fava, M. ; Frank, J. ; Gainer, V. S. ; Gallagher, P. J. ; Gordon, S. D. ; Goryachev, S. ; Gross, M. ; Guipponi, M. ; Henders, A. K. ; Herms, S. ; Hickie, I. B. ; Hoefels, S. ; Hoogendijk, W. ; Iosifescu, D. V. ; Ising, M. ; Jones, I. ; Jones, L. ; Jung-Ying, T. ; Knowles, J. A. ; Kohane, I. S. ; Kohli, M. A. ; Korszun, A. ; Landen, M. ; Lawson, W. B. ; Lewis, G. ; Macintyre, D. ; Maier, W. ; Mattheisen, M. ; McGrath, P. J. ; McIntosh, A. ; McLean, A. ; Middeldorp, C. M. ; Middleton, L. ; Montgomery, G. M. ; Murphy, S. N. ; Nauck, M. ; Nolen, W. A. ; Nyholt, D. R. ; O'Donovan, M. ; Oskarsson, H. ; Pedersen, N. ; Scheftner, W. A. ; Schulz, A. ; Schulze, T. G. ; Shyn, S. I. ; Sigurdsson, E. ; Slager, S. L. ; Smit, J. H. ; Stefansson, H. ; Steffens, M. ; Thorgeirsson, T. ; Tozzi, F. ; Treutlein, J. ; Uhr, M. ; Van Den Oord, E. J. ; Van Grootheest, G. ; Völzke, H. ; Weilburg, J. B. ; Willemsen, G. ; Zitman, F. G. ; Neale, B. ; Daly, M. ; Sullivan, P. F. ; Agrawal, Arpana ; Albrecht, Eva ; Z Alizadeh, Behrooz ; Allik, Jüri ; Amin, Najaf ; Attia, John R. ; Bandinelli, Stefania ; Barnard, John ; Bastardot, Franois ; E Baumeister, Sebastian ; Beauchamp, Jonathan ; Benjamin, Daniel J. ; Benke, Kelly S. ; Bennett, David A. ; Berger, Klaus ; Bielak, Lawrence F. ; Bierut, Laura J. ; Boatman, Jeffrey A. ; Boyle, Patricia A. ; Bültmann, Ute ; Campbell, Harry ; Cesarini, David ; Chabris, Christopher F. ; Cherkas, Lynn ; Chung, Mina K. ; Conley, Dalton ; Cucca, Francesco ; Davey-Smith, George ; Davies, Gail ; De Andrade, Mariza ; De Jager, Philip L. ; De Leeuw, Christiaan ; De Neve, Jan Emmanuel ; Deary, Ian J. ; Dedoussis, George V. ; Deloukas, Panos ; Derringer, Jaime ; Dimitriou, Maria ; Eiriksdottir, Gudny ; Eklund, Niina ; Elderson, Martin F. ; Eriksson, Johan G. ; Evans, Daniel S. ; Evans, David M. ; Faul, Jessica D. ; Fehrmann, Rudolf ; Ferrucci, Luigi ; Fischer, Krista ; Franke, Lude ; Garcia, Melissa E. ; Gieger, Christian ; Gjessing, Hkon K. ; Groenen, Patrick J F ; Grönberg, Henrik ; Gudnason, Vilmundur ; Hägg, Sara ; Hall, Per ; Harris, Jennifer R. ; Harris, Juliette M. ; Harris, Tamara B. ; Hastie, Nicholas D. ; Hayward, Caroline ; Heath, Andrew C. ; Hernandez, Dena G. ; Hoffmann, Wolgang ; Hofman, Adriaan ; Hofman, Albert ; Holle, Rolf ; Holliday, Elizabeth G. ; Holzapfel, Christina ; Iacono, William G. ; Ibrahim-Verbaas, Carla A. ; Illig, Thomas ; Ingelsson, Erik ; Jacobsson, Bo ; Järvelin, Marjo Riitta ; Jhun, Min A. ; Johannesson, Magnus ; Joshi, Peter K. ; Jugessur, Astanand ; Kaakinen, Marika ; Kähönen, Mika ; Kanoni, Stavroula ; Kaprio, Jaakkko ; Kardia, Sharon L R ; Karjalainen, Juha ; Kirkpatrick, Robert M. ; Koellinger, Philipp D. ; Kolcic, Ivana ; Kowgier, Matthew ; Kristiansson, Kati ; Krueger, Robert F. ; Kutalik, Zóltan ; Lahti, Jari ; Laibson, David ; Latvala, Antti ; Launer, Lenore J. ; Lawlor, Debbie A. ; Lethimäki, Terho ; Li, Jingmei ; Lichtenstein, Paul ; Lichtner, Peter K. ; Liewald, David C. ; Lin, Peng ; Lind, Penelope A. ; Liu, Yongmei ; Lohman, Kurt ; Loitfelder, Marisa ; Madden, Pamela A. ; Magnusson, Patrick K E ; Mäkinen, Tomi E. ; Vidal, Pedro Marques ; Martin, Nicolas W. ; Masala, Marco ; McGue, Matt ; McMahon, George ; Meirelles, Osorio ; Meyer, Michelle N. ; Mielck, Andreas ; Milani, Lili ; Miller, Michael B. ; Montgomery, Grant W. ; Mukherjee, Sutapa ; Myhre, Ronny ; Nuotio, Marja Liisa ; Nyholt, Dale R. ; J Oldmeadow, Christopher ; Oostra, Ben A. ; Palmer, Lyle J. ; Palotie, Aarno ; Perola, Markus ; Petrovic, Katja E. ; Peyser, Patricia A. ; Polašek, Ozren ; Posthuma, Danielle ; Preisig, Martin ; Quaye, Lydia ; Räikkönen, Katri ; Raitakari, Olli T. ; Realo, Anu ; Reinmaa, Eva ; Rice, John P. ; Ring, Susan M. ; Ripatti, Samuli ; Rivadeneira, Fernando ; Rizzi, Thais S. ; Rudan, Igor ; Rustichini, Aldo ; Salomaa, Veikko ; Sarin, Antti Pekka ; Schlessinger, David ; Schmidt, Helena ; Schmidt, Reinhold ; Scott, Rodney J. ; Shakhbazov, Konstantin ; Smith, Albert V. ; Smith, Jennifer A. ; Snieder, Harold ; St Pourcain, Beate ; Starr, John M. ; Sul, Jae Hoon ; Surakka, Ida ; Svento, Rauli ; Tanaka, Toshiko ; Terracciano, Antonio ; Teumer, Alexander ; Thurik, A. Roy ; Tiemeier, Henning ; Timpson, Nicholas J. ; Uitterlinden, André G. ; Van Der Loos, Matthijs J H M ; Van Duijn, Cornelia M. ; Van Rooij, Frank J A ; Van Wagoner, David R. ; Vartiainen, Erkki ; Viikari, Jorma ; Visscher, Peter M. ; Vitart, Veronique ; Vollenweider, Peter K. ; Völzke, Henry ; Vonk, Judith M. ; Waeber, Gérard ; Weir, David R. ; Wellmann, Jürgen ; Westra, Harm Jan ; Wichmann, H. Erich ; Widen, Elisabeth ; Wilson, James F. ; Wright, Alan F. ; Yang, Jian ; Yu, Lei ; Zhao, Wei. / The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 6. pp. 735-743.
    @article{59655a85a35f4101958c75b8d4af946c,
    title = "The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects",
    abstract = "An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.",
    author = "Peyrot, {W. J.} and Lee, {S. H.} and Y. Milaneschi and A. Abdellaoui and Byrne, {E. M.} and T. Esko and {De Geus}, {E. J C} and G. Hemani and Hottenga, {J. J.} and S. Kloiber and Levinson, {D. F.} and S. Lucae and Martin, {N. G.} and Medland, {S. E.} and A. Metspalu and L. Milani and Noethen, {M. M.} and Potash, {J. B.} and M. Rietschel and Rietveld, {C. A.} and S. Ripke and J. Shi and G. Willemsen and Z. Zhu and Boomsma, {D. I.} and Wray, {N. R.} and Penninx, {B. W J H} and Lewis, {C. M.} and Hamilton, {S. P.} and Weissman, {M. M.} and G. Breen and Blackwood, {D. H.} and S. Cichon and Heath, {A. C.} and F. Holsboer and Madden, {P. A.} and P. McGuffin and P. Muglia and Pergadia, {M. L.} and D. Lin and B. M{\"u}ller-Myhsok and S. Steinberg and Grabe, {H. J.} and P. Lichtenstein and P. Magnusson and Perlis, {R. H.} and M. Preisig and Smoller, {J. W.} and K. Stefansson and R. Uher and Z. Kutalik and Tansey, {K. E.} and A. Teumer and A. Viktorin and Barnes, {M. R.} and T. Bettecken and Binder, {E. B.} and R. Breuer and Castro, {V. M.} and Churchill, {S. E.} and Coryell, {W. H.} and N. Craddock and Craig, {I. W.} and D. Czamara and F. Degenhardt and Farmer, {A. E.} and M. Fava and J. Frank and Gainer, {V. S.} and Gallagher, {P. J.} and Gordon, {S. D.} and S. Goryachev and M. Gross and M. Guipponi and Henders, {A. K.} and S. Herms and Hickie, {I. B.} and S. Hoefels and W. Hoogendijk and Iosifescu, {D. V.} and M. Ising and I. Jones and L. Jones and T. Jung-Ying and Knowles, {J. A.} and Kohane, {I. S.} and Kohli, {M. A.} and A. Korszun and M. Landen and Lawson, {W. B.} and G. Lewis and D. Macintyre and W. Maier and M. Mattheisen and McGrath, {P. J.} and A. McIntosh and A. McLean and Middeldorp, {C. M.} and L. Middleton and Montgomery, {G. M.} and Murphy, {S. N.} and M. Nauck and Nolen, {W. A.} and Nyholt, {D. R.} and M. O'Donovan and H. Oskarsson and N. Pedersen and Scheftner, {W. A.} and A. Schulz and Schulze, {T. G.} and Shyn, {S. I.} and E. Sigurdsson and Slager, {S. L.} and Smit, {J. H.} and H. Stefansson and M. Steffens and T. Thorgeirsson and F. Tozzi and J. Treutlein and M. Uhr and {Van Den Oord}, {E. J.} and {Van Grootheest}, G. and H. V{\"o}lzke and Weilburg, {J. B.} and G. Willemsen and Zitman, {F. G.} and B. Neale and M. Daly and Sullivan, {P. F.} and Arpana Agrawal and Eva Albrecht and {Z Alizadeh}, Behrooz and J{\"u}ri Allik and Najaf Amin and Attia, {John R.} and Stefania Bandinelli and John Barnard and Franois Bastardot and {E Baumeister}, Sebastian and Jonathan Beauchamp and Benjamin, {Daniel J.} and Benke, {Kelly S.} and Bennett, {David A.} and Klaus Berger and Bielak, {Lawrence F.} and Bierut, {Laura J.} and Boatman, {Jeffrey A.} and Boyle, {Patricia A.} and Ute B{\"u}ltmann and Harry Campbell and David Cesarini and Chabris, {Christopher F.} and Lynn Cherkas and Chung, {Mina K.} and Dalton Conley and Francesco Cucca and George Davey-Smith and Gail Davies and {De Andrade}, Mariza and {De Jager}, {Philip L.} and {De Leeuw}, Christiaan and {De Neve}, {Jan Emmanuel} and Deary, {Ian J.} and Dedoussis, {George V.} and Panos Deloukas and Jaime Derringer and Maria Dimitriou and Gudny Eiriksdottir and Niina Eklund and Elderson, {Martin F.} and Eriksson, {Johan G.} and Evans, {Daniel S.} and Evans, {David M.} and Faul, {Jessica D.} and Rudolf Fehrmann and Luigi Ferrucci and Krista Fischer and Lude Franke and Garcia, {Melissa E.} and Christian Gieger and Gjessing, {Hkon K.} and Groenen, {Patrick J F} and Henrik Gr{\"o}nberg and Vilmundur Gudnason and Sara H{\"a}gg and Per Hall and Harris, {Jennifer R.} and Harris, {Juliette M.} and Harris, {Tamara B.} and Hastie, {Nicholas D.} and Caroline Hayward and Heath, {Andrew C.} and Hernandez, {Dena G.} and Wolgang Hoffmann and Adriaan Hofman and Albert Hofman and Rolf Holle and Holliday, {Elizabeth G.} and Christina Holzapfel and Iacono, {William G.} and Ibrahim-Verbaas, {Carla A.} and Thomas Illig and Erik Ingelsson and Bo Jacobsson and J{\"a}rvelin, {Marjo Riitta} and Jhun, {Min A.} and Magnus Johannesson and Joshi, {Peter K.} and Astanand Jugessur and Marika Kaakinen and Mika K{\"a}h{\"o}nen and Stavroula Kanoni and Jaakkko Kaprio and Kardia, {Sharon L R} and Juha Karjalainen and Kirkpatrick, {Robert M.} and Koellinger, {Philipp D.} and Ivana Kolcic and Matthew Kowgier and Kati Kristiansson and Krueger, {Robert F.} and Z{\'o}ltan Kutalik and Jari Lahti and David Laibson and Antti Latvala and Launer, {Lenore J.} and Lawlor, {Debbie A.} and Terho Lethim{\"a}ki and Jingmei Li and Paul Lichtenstein and Lichtner, {Peter K.} and Liewald, {David C.} and Peng Lin and Lind, {Penelope A.} and Yongmei Liu and Kurt Lohman and Marisa Loitfelder and Madden, {Pamela A.} and Magnusson, {Patrick K E} and M{\"a}kinen, {Tomi E.} and Vidal, {Pedro Marques} and Martin, {Nicolas W.} and Marco Masala and Matt McGue and George McMahon and Osorio Meirelles and Meyer, {Michelle N.} and Andreas Mielck and Lili Milani and Miller, {Michael B.} and Montgomery, {Grant W.} and Sutapa Mukherjee and Ronny Myhre and Nuotio, {Marja Liisa} and Nyholt, {Dale R.} and {J Oldmeadow}, Christopher and Oostra, {Ben A.} and Palmer, {Lyle J.} and Aarno Palotie and Markus Perola and Petrovic, {Katja E.} and Peyser, {Patricia A.} and Ozren Polašek and Danielle Posthuma and Martin Preisig and Lydia Quaye and Katri R{\"a}ikk{\"o}nen and Raitakari, {Olli T.} and Anu Realo and Eva Reinmaa and Rice, {John P.} and Ring, {Susan M.} and Samuli Ripatti and Fernando Rivadeneira and Rizzi, {Thais S.} and Igor Rudan and Aldo Rustichini and Veikko Salomaa and Sarin, {Antti Pekka} and David Schlessinger and Helena Schmidt and Reinhold Schmidt and Scott, {Rodney J.} and Konstantin Shakhbazov and Smith, {Albert V.} and Smith, {Jennifer A.} and Harold Snieder and {St Pourcain}, Beate and Starr, {John M.} and Sul, {Jae Hoon} and Ida Surakka and Rauli Svento and Toshiko Tanaka and Antonio Terracciano and Alexander Teumer and Thurik, {A. Roy} and Henning Tiemeier and Timpson, {Nicholas J.} and Uitterlinden, {Andr{\'e} G.} and {Van Der Loos}, {Matthijs J H M} and {Van Duijn}, {Cornelia M.} and {Van Rooij}, {Frank J A} and {Van Wagoner}, {David R.} and Erkki Vartiainen and Jorma Viikari and Visscher, {Peter M.} and Veronique Vitart and Vollenweider, {Peter K.} and Henry V{\"o}lzke and Vonk, {Judith M.} and G{\'e}rard Waeber and Weir, {David R.} and J{\"u}rgen Wellmann and Westra, {Harm Jan} and Wichmann, {H. Erich} and Elisabeth Widen and Wilson, {James F.} and Wright, {Alan F.} and Jian Yang and Lei Yu and Wei Zhao",
    year = "2015",
    month = "6",
    day = "26",
    doi = "10.1038/mp.2015.50",
    language = "English (US)",
    volume = "20",
    pages = "735--743",
    journal = "Molecular Psychiatry",
    issn = "1359-4184",
    publisher = "Nature Publishing Group",
    number = "6",

    }

    TY - JOUR

    T1 - The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects

    AU - Peyrot, W. J.

    AU - Lee, S. H.

    AU - Milaneschi, Y.

    AU - Abdellaoui, A.

    AU - Byrne, E. M.

    AU - Esko, T.

    AU - De Geus, E. J C

    AU - Hemani, G.

    AU - Hottenga, J. J.

    AU - Kloiber, S.

    AU - Levinson, D. F.

    AU - Lucae, S.

    AU - Martin, N. G.

    AU - Medland, S. E.

    AU - Metspalu, A.

    AU - Milani, L.

    AU - Noethen, M. M.

    AU - Potash, J. B.

    AU - Rietschel, M.

    AU - Rietveld, C. A.

    AU - Ripke, S.

    AU - Shi, J.

    AU - Willemsen, G.

    AU - Zhu, Z.

    AU - Boomsma, D. I.

    AU - Wray, N. R.

    AU - Penninx, B. W J H

    AU - Lewis, C. M.

    AU - Hamilton, S. P.

    AU - Weissman, M. M.

    AU - Breen, G.

    AU - Blackwood, D. H.

    AU - Cichon, S.

    AU - Heath, A. C.

    AU - Holsboer, F.

    AU - Madden, P. A.

    AU - McGuffin, P.

    AU - Muglia, P.

    AU - Pergadia, M. L.

    AU - Lin, D.

    AU - Müller-Myhsok, B.

    AU - Steinberg, S.

    AU - Grabe, H. J.

    AU - Lichtenstein, P.

    AU - Magnusson, P.

    AU - Perlis, R. H.

    AU - Preisig, M.

    AU - Smoller, J. W.

    AU - Stefansson, K.

    AU - Uher, R.

    AU - Kutalik, Z.

    AU - Tansey, K. E.

    AU - Teumer, A.

    AU - Viktorin, A.

    AU - Barnes, M. R.

    AU - Bettecken, T.

    AU - Binder, E. B.

    AU - Breuer, R.

    AU - Castro, V. M.

    AU - Churchill, S. E.

    AU - Coryell, W. H.

    AU - Craddock, N.

    AU - Craig, I. W.

    AU - Czamara, D.

    AU - Degenhardt, F.

    AU - Farmer, A. E.

    AU - Fava, M.

    AU - Frank, J.

    AU - Gainer, V. S.

    AU - Gallagher, P. J.

    AU - Gordon, S. D.

    AU - Goryachev, S.

    AU - Gross, M.

    AU - Guipponi, M.

    AU - Henders, A. K.

    AU - Herms, S.

    AU - Hickie, I. B.

    AU - Hoefels, S.

    AU - Hoogendijk, W.

    AU - Iosifescu, D. V.

    AU - Ising, M.

    AU - Jones, I.

    AU - Jones, L.

    AU - Jung-Ying, T.

    AU - Knowles, J. A.

    AU - Kohane, I. S.

    AU - Kohli, M. A.

    AU - Korszun, A.

    AU - Landen, M.

    AU - Lawson, W. B.

    AU - Lewis, G.

    AU - Macintyre, D.

    AU - Maier, W.

    AU - Mattheisen, M.

    AU - McGrath, P. J.

    AU - McIntosh, A.

    AU - McLean, A.

    AU - Middeldorp, C. M.

    AU - Middleton, L.

    AU - Montgomery, G. M.

    AU - Murphy, S. N.

    AU - Nauck, M.

    AU - Nolen, W. A.

    AU - Nyholt, D. R.

    AU - O'Donovan, M.

    AU - Oskarsson, H.

    AU - Pedersen, N.

    AU - Scheftner, W. A.

    AU - Schulz, A.

    AU - Schulze, T. G.

    AU - Shyn, S. I.

    AU - Sigurdsson, E.

    AU - Slager, S. L.

    AU - Smit, J. H.

    AU - Stefansson, H.

    AU - Steffens, M.

    AU - Thorgeirsson, T.

    AU - Tozzi, F.

    AU - Treutlein, J.

    AU - Uhr, M.

    AU - Van Den Oord, E. J.

    AU - Van Grootheest, G.

    AU - Völzke, H.

    AU - Weilburg, J. B.

    AU - Willemsen, G.

    AU - Zitman, F. G.

    AU - Neale, B.

    AU - Daly, M.

    AU - Sullivan, P. F.

    AU - Agrawal, Arpana

    AU - Albrecht, Eva

    AU - Z Alizadeh, Behrooz

    AU - Allik, Jüri

    AU - Amin, Najaf

    AU - Attia, John R.

    AU - Bandinelli, Stefania

    AU - Barnard, John

    AU - Bastardot, Franois

    AU - E Baumeister, Sebastian

    AU - Beauchamp, Jonathan

    AU - Benjamin, Daniel J.

    AU - Benke, Kelly S.

    AU - Bennett, David A.

    AU - Berger, Klaus

    AU - Bielak, Lawrence F.

    AU - Bierut, Laura J.

    AU - Boatman, Jeffrey A.

    AU - Boyle, Patricia A.

    AU - Bültmann, Ute

    AU - Campbell, Harry

    AU - Cesarini, David

    AU - Chabris, Christopher F.

    AU - Cherkas, Lynn

    AU - Chung, Mina K.

    AU - Conley, Dalton

    AU - Cucca, Francesco

    AU - Davey-Smith, George

    AU - Davies, Gail

    AU - De Andrade, Mariza

    AU - De Jager, Philip L.

    AU - De Leeuw, Christiaan

    AU - De Neve, Jan Emmanuel

    AU - Deary, Ian J.

    AU - Dedoussis, George V.

    AU - Deloukas, Panos

    AU - Derringer, Jaime

    AU - Dimitriou, Maria

    AU - Eiriksdottir, Gudny

    AU - Eklund, Niina

    AU - Elderson, Martin F.

    AU - Eriksson, Johan G.

    AU - Evans, Daniel S.

    AU - Evans, David M.

    AU - Faul, Jessica D.

    AU - Fehrmann, Rudolf

    AU - Ferrucci, Luigi

    AU - Fischer, Krista

    AU - Franke, Lude

    AU - Garcia, Melissa E.

    AU - Gieger, Christian

    AU - Gjessing, Hkon K.

    AU - Groenen, Patrick J F

    AU - Grönberg, Henrik

    AU - Gudnason, Vilmundur

    AU - Hägg, Sara

    AU - Hall, Per

    AU - Harris, Jennifer R.

    AU - Harris, Juliette M.

    AU - Harris, Tamara B.

    AU - Hastie, Nicholas D.

    AU - Hayward, Caroline

    AU - Heath, Andrew C.

    AU - Hernandez, Dena G.

    AU - Hoffmann, Wolgang

    AU - Hofman, Adriaan

    AU - Hofman, Albert

    AU - Holle, Rolf

    AU - Holliday, Elizabeth G.

    AU - Holzapfel, Christina

    AU - Iacono, William G.

    AU - Ibrahim-Verbaas, Carla A.

    AU - Illig, Thomas

    AU - Ingelsson, Erik

    AU - Jacobsson, Bo

    AU - Järvelin, Marjo Riitta

    AU - Jhun, Min A.

    AU - Johannesson, Magnus

    AU - Joshi, Peter K.

    AU - Jugessur, Astanand

    AU - Kaakinen, Marika

    AU - Kähönen, Mika

    AU - Kanoni, Stavroula

    AU - Kaprio, Jaakkko

    AU - Kardia, Sharon L R

    AU - Karjalainen, Juha

    AU - Kirkpatrick, Robert M.

    AU - Koellinger, Philipp D.

    AU - Kolcic, Ivana

    AU - Kowgier, Matthew

    AU - Kristiansson, Kati

    AU - Krueger, Robert F.

    AU - Kutalik, Zóltan

    AU - Lahti, Jari

    AU - Laibson, David

    AU - Latvala, Antti

    AU - Launer, Lenore J.

    AU - Lawlor, Debbie A.

    AU - Lethimäki, Terho

    AU - Li, Jingmei

    AU - Lichtenstein, Paul

    AU - Lichtner, Peter K.

    AU - Liewald, David C.

    AU - Lin, Peng

    AU - Lind, Penelope A.

    AU - Liu, Yongmei

    AU - Lohman, Kurt

    AU - Loitfelder, Marisa

    AU - Madden, Pamela A.

    AU - Magnusson, Patrick K E

    AU - Mäkinen, Tomi E.

    AU - Vidal, Pedro Marques

    AU - Martin, Nicolas W.

    AU - Masala, Marco

    AU - McGue, Matt

    AU - McMahon, George

    AU - Meirelles, Osorio

    AU - Meyer, Michelle N.

    AU - Mielck, Andreas

    AU - Milani, Lili

    AU - Miller, Michael B.

    AU - Montgomery, Grant W.

    AU - Mukherjee, Sutapa

    AU - Myhre, Ronny

    AU - Nuotio, Marja Liisa

    AU - Nyholt, Dale R.

    AU - J Oldmeadow, Christopher

    AU - Oostra, Ben A.

    AU - Palmer, Lyle J.

    AU - Palotie, Aarno

    AU - Perola, Markus

    AU - Petrovic, Katja E.

    AU - Peyser, Patricia A.

    AU - Polašek, Ozren

    AU - Posthuma, Danielle

    AU - Preisig, Martin

    AU - Quaye, Lydia

    AU - Räikkönen, Katri

    AU - Raitakari, Olli T.

    AU - Realo, Anu

    AU - Reinmaa, Eva

    AU - Rice, John P.

    AU - Ring, Susan M.

    AU - Ripatti, Samuli

    AU - Rivadeneira, Fernando

    AU - Rizzi, Thais S.

    AU - Rudan, Igor

    AU - Rustichini, Aldo

    AU - Salomaa, Veikko

    AU - Sarin, Antti Pekka

    AU - Schlessinger, David

    AU - Schmidt, Helena

    AU - Schmidt, Reinhold

    AU - Scott, Rodney J.

    AU - Shakhbazov, Konstantin

    AU - Smith, Albert V.

    AU - Smith, Jennifer A.

    AU - Snieder, Harold

    AU - St Pourcain, Beate

    AU - Starr, John M.

    AU - Sul, Jae Hoon

    AU - Surakka, Ida

    AU - Svento, Rauli

    AU - Tanaka, Toshiko

    AU - Terracciano, Antonio

    AU - Teumer, Alexander

    AU - Thurik, A. Roy

    AU - Tiemeier, Henning

    AU - Timpson, Nicholas J.

    AU - Uitterlinden, André G.

    AU - Van Der Loos, Matthijs J H M

    AU - Van Duijn, Cornelia M.

    AU - Van Rooij, Frank J A

    AU - Van Wagoner, David R.

    AU - Vartiainen, Erkki

    AU - Viikari, Jorma

    AU - Visscher, Peter M.

    AU - Vitart, Veronique

    AU - Vollenweider, Peter K.

    AU - Völzke, Henry

    AU - Vonk, Judith M.

    AU - Waeber, Gérard

    AU - Weir, David R.

    AU - Wellmann, Jürgen

    AU - Westra, Harm Jan

    AU - Wichmann, H. Erich

    AU - Widen, Elisabeth

    AU - Wilson, James F.

    AU - Wright, Alan F.

    AU - Yang, Jian

    AU - Yu, Lei

    AU - Zhao, Wei

    PY - 2015/6/26

    Y1 - 2015/6/26

    N2 - An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

    AB - An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

    UR - http://www.scopus.com/inward/record.url?scp=84930226539&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84930226539&partnerID=8YFLogxK

    U2 - 10.1038/mp.2015.50

    DO - 10.1038/mp.2015.50

    M3 - Article

    VL - 20

    SP - 735

    EP - 743

    JO - Molecular Psychiatry

    JF - Molecular Psychiatry

    SN - 1359-4184

    IS - 6

    ER -