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GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

ABSTRACT: A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ? 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ?2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

SUBMITTER: Rietveld CA

PROVIDER: S-EPMC3751588 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

Rietveld Cornelius A CA Medland Sarah E SE Derringer Jaime J Yang Jian J Esko Tõnu T Martin Nicolas W NW Westra Harm-Jan HJ Shakhbazov Konstantin K Abdellaoui Abdel A Agrawal Arpana A Albrecht Eva E Alizadeh Behrooz Z BZ Amin Najaf N Barnard John J Baumeister Sebastian E SE Benke Kelly S KS Bielak Lawrence F LF Boatman Jeffrey A JA Boyle Patricia A PA Davies Gail G de Leeuw Christiaan C Eklund Niina N Evans Daniel S DS Ferhmann Rudolf R Fischer Krista K Gieger Christian C Gjessing Håkon K HK Hägg Sara S Harris Jennifer R JR Hayward Caroline C Holzapfel Christina C Ibrahim-Verbaas Carla A CA Ingelsson Erik E Jacobsson Bo B Joshi Peter K PK Jugessur Astanand A Kaakinen Marika M Kanoni Stavroula S Karjalainen Juha J Kolcic Ivana I Kristiansson Kati K Kutalik Zoltán Z Lahti Jari J Lee Sang H SH Lin Peng P Lind Penelope A PA Liu Yongmei Y Lohman Kurt K Loitfelder Marisa M McMahon George G Vidal Pedro Marques PM Meirelles Osorio O Milani Lili L Myhre Ronny R Nuotio Marja-Liisa ML Oldmeadow Christopher J CJ Petrovic Katja E KE Peyrot Wouter J WJ Polasek Ozren O Quaye Lydia L Reinmaa Eva E Rice John P JP Rizzi Thais S TS Schmidt Helena H Schmidt Reinhold R Smith Albert V AV Smith Jennifer A JA Tanaka Toshiko T Terracciano Antonio A van der Loos Matthijs J H M MJ Vitart Veronique V Völzke Henry H Wellmann Jürgen J Yu Lei L Zhao Wei W Allik Jüri J Attia John R JR Bandinelli Stefania S Bastardot François F Beauchamp Jonathan J Bennett David A DA Berger Klaus K Bierut Laura J LJ Boomsma Dorret I DI Bültmann Ute U Campbell Harry H Chabris Christopher F CF Cherkas Lynn L Chung Mina K MK Cucca Francesco F de Andrade Mariza M De Jager Philip L PL De Neve Jan-Emmanuel JE Deary Ian J IJ Dedoussis George V GV Deloukas Panos P Dimitriou Maria M Eiríksdóttir Guðny G Elderson Martin F MF Eriksson Johan G JG Evans David M DM Faul Jessica D JD Ferrucci Luigi L Garcia Melissa E ME Grönberg Henrik H Guðnason Vilmundur V Hall Per P Harris Juliette M JM Harris Tamara B TB Hastie Nicholas D ND Heath Andrew C AC Hernandez Dena G DG Hoffmann Wolfgang W Hofman Adriaan A Holle Rolf R Holliday Elizabeth G EG Hottenga Jouke-Jan JJ Iacono William G WG Illig Thomas T Järvelin Marjo-Riitta MR Kähönen Mika M Kaprio Jaakko J Kirkpatrick Robert M RM Kowgier Matthew M Latvala Antti A Launer Lenore J LJ Lawlor Debbie A DA Lehtimäki Terho T Li Jingmei J Lichtenstein Paul P Lichtner Peter P Liewald David C DC Madden Pamela A PA Magnusson Patrik K E PK Mäkinen Tomi E TE Masala Marco M McGue Matt M Metspalu Andres A Mielck Andreas A Miller Michael B MB Montgomery Grant W GW Mukherjee Sutapa S Nyholt Dale R DR Oostra Ben A BA Palmer Lyle J LJ Palotie Aarno A Penninx Brenda W J H BW Perola Markus M Peyser Patricia A PA Preisig Martin M Räikkönen Katri K Raitakari Olli T OT Realo Anu A Ring Susan M SM Ripatti Samuli S Rivadeneira Fernando F Rudan Igor I Rustichini Aldo A Salomaa Veikko V Sarin Antti-Pekka AP Schlessinger David D Scott Rodney J RJ Snieder Harold H St Pourcain Beate B Starr John M JM Sul Jae Hoon JH Surakka Ida I Svento Rauli R Teumer Alexander A Tiemeier Henning H van Rooij Frank J A FJ Van Wagoner David R DR Vartiainen Erkki E Viikari Jorma J Vollenweider Peter P Vonk Judith M JM Waeber Gérard G Weir David R DR Wichmann H-Erich HE Widen Elisabeth E Willemsen Gonneke G Wilson James F JF Wright Alan F AF Conley Dalton D Davey-Smith George G Franke Lude L Groenen Patrick J F PJ Hofman Albert A Johannesson Magnus M Kardia Sharon L R SL Krueger Robert F RF Laibson David D Martin Nicholas G NG Meyer Michelle N MN Posthuma Danielle D Thurik A Roy AR Timpson Nicholas J NJ Uitterlinden André G AG van Duijn Cornelia M CM Visscher Peter M PM Benjamin Daniel J DJ Cesarini David D Koellinger Philipp D PD

Science (New York, N.Y.) 20130530 6139

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of ...[more]

PMID: 23722424

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Project description:Neuroimaging investigations have revealed interindividual variations in anatomy, metabolism, activity, and connectivity of specific cortical association areas through which years of education (YoE), as a common proxy of cognitive reserve, may operate in the face of age- or pathology-associated brain changes. However, the associated molecular properties of YoE-related brain regions and the biological pathways involved remain poorly understood. In the present study we first identified brain areas that showed an association between cortical thickness and YoE among 122 cognitively healthy older human individuals (87 female). We subsequently characterized molecular properties of these regions by studying brain-wide microarray measurements of regional gene expression. In accordance with previous studies, we observed that YoE were associated with higher cortical thickness in medial prefrontal, anterior cingulate, and orbitofrontal areas. Compared with the rest of the cortex, these regions exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in ionotropic and metabotropic neurotransmission as well as activation of immune response. Our genome-wide expression profile analysis of YoE-related brain regions points to distinct molecular pathways that may underlie a higher capacity for plastic changes in response to lifetime intellectual enrichment and potentially also a higher resilience to age-related pathologic brain changes.SIGNIFICANCE STATEMENT We combined a neuroimaging-based analysis with a transcriptome-wide gene expression approach to investigate the molecular-functional properties of cortical regions associated with educational attainment, as a commonly used proxy for cognitive reserve, in older individuals. The strongest association with education was observed in specific areas of the medial prefrontal cortex, and these areas exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in neurotransmission and immune responses. These findings complement previous neuroimaging studies in the field and point to novel biological pathways that may mediate the beneficial effects of high educational attainment on adaptability to cope with, or prevent, age-related brain changes. The identified genes and pathways now warrant further exploration in mechanistic studies.

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GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

Publications

GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

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