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

W J Peyrot¹, S H Lee², Y Milaneschi¹, A Abdellaoui³, E M Byrne², T Esko⁴, E J C de Geus³, G Hemani⁵, J J Hottenga³, S Kloiber⁶, D F Levinson⁷, S Lucae⁶; Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator); N G Martin⁸, S E Medland⁸, A Metspalu⁴, L Milani⁴, M M Noethen⁹, J B Potash¹⁰, M Rietschel¹¹, C A Rietveld¹², S Ripke¹³, J Shi¹⁴; Social Science Genetic Association Consortium Corporate Collaborator; G Willemsen³, Z Zhu², D I Boomsma³, N R Wray², B W J H Penninx¹; Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator; Social Science Genetic Association Consortium Corporate Collaborator

Collaborators, Affiliations

Collaborators

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, François 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, Håkon 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

Affiliations

¹ Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
² The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.
³ Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
⁴ 1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Division of Endocrinology and Center of Basic and Translational Obesity Research, Children's Hospital Boston, Boston; Department of Genetics, Harvard Medical School, Boston; Broad Institute, Cambridge, MA, USA.
⁵ 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia [2] MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK.
⁶ Max Planck Institute of Psychiatry, Munich, Germany.
⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁸ Genetic Epidemiology Unit, QIMR Berhgofer Institute of Medical Research, Brisbane, Queensland, Australia.
⁹ Institute of Human Genetics, University of Bonn, Bonn, Germany.
¹⁰ Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
¹¹ Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
¹² 1] Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands [2] Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands.
¹³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁴ Biostatistics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD, USA.

PMID: 25917368
PMCID: PMC4610719
DOI: 10.1038/mp.2015.50

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

W J Peyrot et al. Mol Psychiatry. 2015 Jun.

. 2015 Jun;20(6):735-43.

doi: 10.1038/mp.2015.50. Epub 2015 Apr 28.

Authors

Collaborators

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, François 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, Håkon 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

Affiliations

¹ Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
² The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.
³ Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
⁴ 1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Division of Endocrinology and Center of Basic and Translational Obesity Research, Children's Hospital Boston, Boston; Department of Genetics, Harvard Medical School, Boston; Broad Institute, Cambridge, MA, USA.
⁵ 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia [2] MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK.
⁶ Max Planck Institute of Psychiatry, Munich, Germany.
⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁸ Genetic Epidemiology Unit, QIMR Berhgofer Institute of Medical Research, Brisbane, Queensland, Australia.
⁹ Institute of Human Genetics, University of Bonn, Bonn, Germany.
¹⁰ Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
¹¹ Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
¹² 1] Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands [2] Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands.
¹³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁴ Biostatistics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD, USA.

PMID: 25917368
PMCID: PMC4610719
DOI: 10.1038/mp.2015.50

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.

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Conflict of interest statement

CONFLICTS OF INTEREST

All other co-authors have no conflicts of interest.

Figures

**Figure 1. Forest plot of the phenotypic association between EA and MDD**
The OR for MDD per SD increase in EA is displayed for the individual cohorts, as well as for the overall sample. The ORs were estimated with logistic regression of MDD on the corrected EA z-scores, which were defined as the standardized residuals of the regression of EA on sex, year of birth (YOB), YOB², YOB³, and the interaction of sex with YOB, YOB², and YOB³.

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

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