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, Dale 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, 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

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23 Scopus citations

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

All Science Journal Classification (ASJC) codes

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

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