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 language | English (US) |
|---|---|
| Pages (from-to) | 735-743 |
| Number of pages | 9 |
| Journal | Molecular psychiatry |
| Volume | 20 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 26 2015 |
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Molecular Biology
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In: Molecular psychiatry, Vol. 20, No. 6, 26.06.2015, p. 735-743.
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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.
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AU - Hemani, G.
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AU - Medland, S. E.
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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.
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AU - Cichon, S.
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AU - Madden, Pamela A.
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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.
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AU - Kutalik, Z.
AU - Tansey, K. E.
AU - Teumer, A.
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AU - Barnes, M. R.
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AU - Binder, E. B.
AU - Breuer, R.
AU - Castro, V. M.
AU - Churchill, S. E.
AU - Coryell, W. H.
AU - Craddock, N.
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AU - Czamara, D.
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AU - Lewis, G.
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AU - Maier, W.
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AU - McLean, A.
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AU - Steffens, M.
AU - Thorgeirsson, T.
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AU - Völzke, H.
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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.
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AU - Boyle, Patricia A.
AU - Bültmann, Ute
AU - Campbell, Harry
AU - Cesarini, David
AU - Chabris, Christopher F.
AU - Cherkas, Lynn
AU - Chung, Mina K.
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AU - Davey-Smith, George
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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
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AU - Gudnason, Vilmundur
AU - Hägg, Sara
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AU - Hastie, Nicholas D.
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AU - Hofman, Adriaan
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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
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AU - Kristiansson, Kati
AU - Krueger, Robert F.
AU - Kutalik, Zóltan
AU - Lahti, Jari
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AU - Liu, Yongmei
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AU - Loitfelder, Marisa
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 - Miller, Michael B.
AU - Montgomery, Grant W.
AU - Mukherjee, Sutapa
AU - Myhre, Ronny
AU - Nuotio, Marja Liisa
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
C2 - 25917368
AN - SCOPUS:84930226539
SN - 1359-4184
VL - 20
SP - 735
EP - 743
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 6
ER -