Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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25917368
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.
DATE PUBLISHED
2015 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/11/27
revised 2015/02/28
accepted 2015/03/24
aheadofprint 2015/04/28
entrez 2015/04/29 06:00
pubmed 2015/04/29 06:00
medline 2016/02/10 06:00
pmc-release 2016/06/01 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Peyrot WJ
Lee SH
Milaneschi Y
Abdellaoui A
Byrne EM
Esko T
de Geus EJ
Hemani G
Hottenga JJ
Kloiber S
Levinson DF
Lucae S
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator)
Martin NG
Medland SE
Metspalu A
Milani L
Noethen MM
Potash JB
Rietschel M
Rietveld CA
Ripke S
Shi J
Social Science Genetic Association Consortium Corporate Collaborator
Willemsen G
Zhu Z
Boomsma DI
Wray NR
Penninx BW
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator
Social Science Genetic Association Consortium Corporate Collaborator
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Lewis C M CM
Hamilton S P SP
Weissman M M MM
Breen G G
Blackwood D H DH
Cichon S S
Heath A C AC
Holsboer F F
Madden P A PA
McGuffin P P
Muglia P P
Pergadia M L ML
Lin D D
Müller-Myhsok B B
Steinberg S S
Grabe H J HJ
Lichtenstein P P
Magnusson P P
Perlis R H RH
Preisig M M
Smoller J W JW
Stefansson K K
Uher R R
Kutalik Z Z
Tansey K E KE
Teumer A A
Viktorin A A
Barnes M R MR
Bettecken T T
Binder E B EB
Breuer R R
Castro V M VM
Churchill S E SE
Coryell W H WH
Craddock N N
Craig I W IW
Czamara D D
Degenhardt F F
Farmer A E AE
Fava M M
Frank J J
Gainer V S VS
Gallagher P J PJ
Gordon S D SD
Goryachev S S
Gross M M
Guipponi M M
Henders A K AK
Herms S S
Hickie I B IB
Hoefels S S
Hoogendijk W W
Iosifescu D V DV
Ising M M
Jones I I
Jones L L
Jung-Ying T T
Knowles J A JA
Kohane I S IS
Kohli M A MA
Korszun A A
Landen M M
Lawson W B WB
Lewis G G
Macintyre D D
Maier W W
Mattheisen M M
McGrath P J PJ
McIntosh A A
McLean A A
Middeldorp C M CM
Middleton L L
Montgomery G M GM
Murphy S N SN
Nauck M M
Nolen W A WA
Nyholt D R DR
O'Donovan M M
Oskarsson H H
Pedersen N N
Scheftner W A WA
Schulz A A
Schulze T G TG
Shyn S I SI
Sigurdsson E E
Slager S L SL
Smit J H JH
Stefansson H H
Steffens M M
Thorgeirsson T T
Tozzi F F
Treutlein J J
Uhr M M
van den Oord E J EJ
Van Grootheest G G
Völzke H H
Weilburg J B JB
Willemsen G G
Zitman F G FG
Neale B B
Daly M M
Sullivan P F PF
Agrawal Arpana A
Albrecht Eva E
Alizadeh Behrooz Z BZ
Allik Jüri J
Amin Najaf N
Attia John R JR
Bandinelli Stefania S
Barnard John J
Bastardot François F
Baumeister Sebastian E SE
Beauchamp Jonathan J
Benjamin Daniel J DJ
Benke Kelly S KS
Bennett David A DA
Berger Klaus K
Bielak Lawrence F LF
Bierut Laura J LJ
Boatman Jeffrey A JA
Boyle Patricia A PA
Bültmann Ute U
Campbell Harry H
Cesarini David D
Chabris Christopher F CF
Cherkas Lynn L
Chung Mina K MK
Conley Dalton D
Cucca Francesco F
Davey-Smith George G
Davies Gail G
de Andrade Mariza M
De Jager Philip L PL
de Leeuw Christiaan C
De Neve Jan-Emmanuel JE
Deary Ian J IJ
Dedoussis George V GV
Deloukas Panos P
Derringer Jaime J
Dimitriou Maria M
Eiriksdottir Gudny G
Eklund Niina N
Elderson Martin F MF
Eriksson Johan G JG
Evans Daniel S DS
Evans David M DM
Faul Jessica D JD
Fehrmann Rudolf R
Ferrucci Luigi L
Fischer Krista K
Franke Lude L
Garcia Melissa E ME
Gieger Christian C
Gjessing HÃ¥kon K HK
Groenen Patrick J F PJ
Grönberg Henrik H
Gudnason Vilmundur V
Hägg Sara S
Hall Per P
Harris Jennifer R JR
Harris Juliette M JM
Harris Tamara B TB
Hastie Nicholas D ND
Hayward Caroline C
Heath Andrew C AC
Hernandez Dena G DG
Hoffmann Wolgang W
Hofman Adriaan A
Hofman Albert A
Holle Rolf R
Holliday Elizabeth G EG
Holzapfel Christina C
Iacono William G WG
Ibrahim-Verbaas Carla A CA
Illig Thomas T
Ingelsson Erik E
Jacobsson Bo B
Järvelin Marjo-Riitta MR
Jhun Min A MA
Johannesson Magnus M
Joshi Peter K PK
Jugessur Astanand A
Kaakinen Marika M
Kähönen Mika M
Kanoni Stavroula S
Kaprio Jaakkko J
Kardia Sharon L R SL
Karjalainen Juha J
Kirkpatrick Robert M RM
Koellinger Philipp D PD
Kolcic Ivana I
Kowgier Matthew M
Kristiansson Kati K
Krueger Robert F RF
Kutalik Zóltan Z
Lahti Jari J
Laibson David D
Latvala Antti A
Launer Lenore J LJ
Lawlor Debbie A DA
Lethimäki Terho T
Li Jingmei J
Lichtenstein Paul P
Lichtner Peter K PK
Liewald David C DC
Lin Peng P
Lind Penelope A PA
Liu Yongmei Y
Lohman Kurt K
Loitfelder Marisa M
Madden Pamela A PA
Magnusson Patrick K E PK
Mäkinen Tomi E TE
Vidal Pedro Marques PM
Martin Nicolas W NW
Masala Marco M
McGue Matt M
McMahon George G
Meirelles Osorio O
Meyer Michelle N MN
Mielck Andreas A
Milani Lili L
Miller Michael B MB
Montgomery Grant W GW
Mukherjee Sutapa S
Myhre Ronny R
Nuotio Marja-Liisa ML
Nyholt Dale R DR
Oldmeadow Christopher J CJ
Oostra Ben A BA
Palmer Lyle J LJ
Palotie Aarno A
Perola Markus M
Petrovic Katja E KE
Peyser Patricia A PA
Polašek Ozren O
Posthuma Danielle D
Preisig Martin M
Quaye Lydia L
Räikkönen Katri K
Raitakari Olli T OT
Realo Anu A
Reinmaa Eva E
Rice John P JP
Ring Susan M SM
Ripatti Samuli S
Rivadeneira Fernando F
Rizzi Thais S TS
Rudan Igor I
Rustichini Aldo A
Salomaa Veikko V
Sarin Antti-Pekka AP
Schlessinger David D
Schmidt Helena H
Schmidt Reinhold R
Scott Rodney J RJ
Shakhbazov Konstantin K
Smith Albert V AV
Smith Jennifer A JA
Snieder Harold H
Pourcain Beate St BS
Starr John M JM
Sul Jae Hoon JH
Surakka Ida I
Svento Rauli R
Tanaka Toshiko T
Terracciano Antonio A
Teumer Alexander A
Thurik A Roy AR
Tiemeier Henning H
Timpson Nicholas J NJ
Uitterlinden André G AG
van der Loos Matthijs J H M MJ
van Duijn Cornelia M CM
van Rooij Frank J A FJ
Van Wagoner David R DR
Vartiainen Erkki E
Viikari Jorma J
Visscher Peter M PM
Vitart Veronique V
Vollenweider Peter K PK
Völzke Henry H
Vonk Judith M JM
Waeber Gérard G
Weir David R DR
Wellmann Jürgen J
Westra Harm-Jan HJ
Wichmann H-Erich HE
Widen Elisabeth E
Wilson James F JF
Wright Alan F AF
Yang Jian J
Yu Lei L
Zhao Wei W
JOURNAL
VOLUME: 20
ISSUE: 6
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2015
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
076113 Wellcome Trust United Kingdom
085475 Wellcome Trust United Kingdom
104036 Wellcome Trust United Kingdom
AA07535 NIAAA NIH HHS United States
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G0000647 Medical Research Council United Kingdom
G0701420 Medical Research Council United Kingdom
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GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Cohort Studies
Depressive Disorder, Major psychology
Educational Status psychology
Estonia epidemiology
Female epidemiology
Gene-Environment Interaction epidemiology
Genetic Association Studies epidemiology
Genotype epidemiology
Humans epidemiology
Likelihood Functions epidemiology
Male epidemiology
Middle Aged epidemiology
Netherlands epidemiology
Odds Ratio epidemiology
Polymorphism, Single Nucleotide genetics
Psychiatric Status Rating Scales genetics
Regression Analysis genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS723108 [Available on 06/01/16] NLM
PMC4610719 [Available on 06/01/16] NLM
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