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

2015

Peyrot, W J

Lee, Sang Hong

Levinson, D F

Steffens, M

Thorgeirsson, T

Tozzi, F

Treutlein, J

Uhr, M

van den Oord, E J

Van Grootheest, G

Volzke, H

Weilburg, J B

Willemsen, G

Lucae, S

Zitman, F G

Neale, B

Daly, M

Sullivan, P F

Martin, N G

Medland, S E

Metspalu, A

Milani, L

Noethen, M M

Potash, J B

Lewis, C M

Rietschel, M

Rietveld, C A

Ripke, S

Shi, J

Agrawal, Arpana

Albrecht, Eva

Alizadeh, Behrooz Z

Allik, Juri

Amin, Najaf

Attia, John R

Hamilton, S P

Bandinelli, Stefania

Barnard, John

Bastardot, Francois

Baumeister, Sebastian E

Beauchamp, Jonathan

Benjamin, Daniel J

Benke, Kelly S

Bennett, David A

Berger, Klaus

Bielak, Lawrence F

Weissman, M M

Bierut, Laura J

Boatman, Jeffrey A

Boyle, Patricia A

Bultmann, Ute

Campbell, Harry

Cesarini, David

Chabris, Christopher F

Cherkas, Lynn

Chung, Mina K

Conley, Dalton

Breen, G

Cucca, Francesco

Davey-Smith, George

Davies, Gail

Andrade, Mariza de

De Jager, Philip L

de Leeuw, Christiaan

De Neve, Jan-Emmanuel

Deary, Ian J

Dedoussis, George V

Deloukas, Panos

Blackwood, D H

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

Cichon, S

Ferrucci, Luigi

Fischer, Krista

Franke, Lude

Garcia, Melissa E

Gieger, Christian

Gjessing, Hakon K

Groenen, Patrick J F

Gronberg, Henrik

Gudnason, Vilmundur

Hagg, Sara

Heath, A C

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

Holsboer, F

Hofman, Albert

Holle, Rolf

Holliday, Elizabeth G

Holzapfel, Christina

Iacono, William G

Ibrahim-Verbaas, Carla A

Illig, Thomas

Ingelsson, Erik

Jacobsson, Bo

Jarvelin, Marjo-Riitta

Milaneschi, Y

Madden, P A

Jhun, Min A

Johannesson, Magnus

Joshi, Peter K

Jugessur, Astanand

Kaakinen, Marika

Kahonen, Mika

Kanoni, Stavroula

Kaprio, Jaakkko

Kardia, Sharon L R

Karjalainen, Juha

McGuffin, P

Kirkpatrick, Robert M

Koellinger, Philipp D

Kolcic, Ivana

Kowgier, Matthew

Kristiansson, Kati

Krueger, Robert F

Kutalik, Zoltan

Lahti, Jari

Laibson, David

Latvala, Antti

Muglia, P

Launer, Lenore J

Lawlor, Debbie A

Lethimaki, Terho

Li, Jingmei

Lichtenstein, Paul

Lichtner, Peter K

Liewald, David C

Lin, Peng

Lind, Penelope A

Liu, Yongmei

Pergadia, M L

Lohman, Kurt

Loitfelder, Marisa

Madden, Pamela A

Magnusson, Patrick K E

Makinen, Tomi E

Vidal, Pedro Marques

Martin, Nicolas W

Masala, Marco

McGue, Matt

McMahon, George

Lin, D

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

Muller-Myhsok, B

Oldmeadow, Christopher J

Oostra, Ben A

Palmer, Lyle J

Palotie, Aarno

Perola, Markus

Petrovic, Katja E

Peyser, Patricia A

Polasek, Ozren

Posthuma, Danielle

Preisig, Martin

Steinberg, S

Quaye, Lydia

Raikkonen, Katri

Raitakari, Olli T

Realo, Anu

Reinmaa, Eva

Rice, John P

Ring, Susan M

Ripatti, Samuli

Rivadeneira, Fernando

Rizzi, Thais S

Grabe, H J

Rudan, Igor

Rustichini, Aldo

Salomaa, Veikko

Sarin, Antti-Pekka

Schlessinger, David

Schmidt, Helena

Schmidt, Reinhold

Scott, Rodney J

Shakhbazov, Konstantin

Smith, Albert V

Lichtenstein, P

Smith, Jennifer A

Snieder, Harold

St Pourcain, Beate

Starr, John M

Sul, Jae Hoon

Surakka, Ida

Svento, Rauli

Tanaka, Toshiko

Terracciano, Antonio

Teumer, Alexander

Magnusson, P

Thurik, A Roy

Tiemeier, Henning

Timpson, Nicholas J

Uitterlinden, Andre 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

Abdellaoui, A

Perlis, R H

Visscher, Peter M

Vitart, Veronique

Vollenweider, Peter K

Volzke, Henry

Vonk, Judith M

Waeber, Gerard

Weir, David R

Wellmann, Jurgen

Westra, Harm-Jan

Wichmann, H-Erich

Preisig, M

Widen, Elisabeth

Wilson, James F

Wright, Alan F

Yang, Jian

Yu, Lei

Zhao, Wei

Willemsen, G

Zhu, Z

Boomsma, D I

Wray, N R

Smoller, J W

Penninx, B W J H

Stefansson, K

Uher, R

Kutalik, Z

Tansey, K E

Teumer, A

Viktorin, A

Barnes, M R

Byrne, E M

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

Esko, T

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

de Geus, E J C

Herms, S

Hickie, I B

Hoefels, S

Hoogendijk, W

Iosifescu, D V

Ising, M

Jones, I

Jones, L

Jung-Ying, T

Knowles, J A

Hemani, G

Kohane, I S

Kohli, M A

Korszun, A

Landen, M

Lawson, W B

Lewis, G

Macintyre, D

Maier, W

Mattheisen, M

McGrath, P J

Hottenga, J 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

Kloiber, S

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

Journal Article

en

Publication

Nature Publishing Group

United Kingdom

10.1038/mp.2015.50

une:19096

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.

link

Molecular Psychiatry, 20(6), p. 735-743

1476-5578

1359-4184

735

743