Genome-wide association study identifies 74 loci associated with educational attainment

Okbay, Aysu, Beauchamp, Jonathan P, Fontana, Mark Alan, Lee, James J, Pers, Tune H, Rietveld, Cornelius A, Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Meddens, S Fleur W, Oskarsson, Sven, Pickrell, Joseph K, Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S, Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H, Pina Concas, Maria, Derringer, Jaime, Furlotte, Nicholas A, Galesloot, Tessel E, Girotto, Giorgia, Gupta, Richa, Hall, Leanne M, Harris, Sarah E, Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E, Kaasik, Kadri, Kalafati, Ioanna P, Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J van der, deLeeuw, Christiaan, Lind, Penelope A, Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B, van der Most, Peter J, Oldmeadow, Christopher, Payton, Antony, Pervjakova, Natalia, Peyrot, Wouter J, Qian, Yong, Raitakari, Olli, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E, Shi, Jianxin, Smith, Albert V, Poot, Raymond A, St Pourcain, Beate, Teumer, Alexander, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Westra, Harm-Jan, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z, Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E, Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A, Campbell, Harry, Cappuccio, Francesco P, Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eibich, Peter, Eisele, Lewin, Eklund, Niina, Evans, David M, Faul, Jessica D, Feitosa, Mary F, Forstner, Andreas J, Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V, Harris, Tamara B, Heath, Andrew C, Hocking, Lynne J, Holliday, Elizabeth G, Homuth, Georg, Horan, Michael A, Hottenga, Jouke-Jan, de Jager, Philip L, Joshi, Peter K, Jugessur, Astanand, Kaakinen, Marika A, Kähönen, Mika, Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus ALM, Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T, Kroh, Martin, Kutalik, Zoltan, Latvala, Antti, Launer, Lenore J, Lebreton, Maël P, Levinson, Douglas F, Lichtenstein, Paul, Lichtner, Peter, Liewald, David CM, Cohort Study, LifeLines, Loukola, Anu, Madden, Pamela A, Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E, Marques-Vidal, Pedro, Meddens, Gerardus A, McMahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Milani, Lili, Montgomery, Grant W, Myhre, Ronny, Nelson, Christopher P, Nyholt, Dale R, Ollier, William ER, Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L, Petrovic, Katja E, Porteous, David J, Räikkönen, Katri, Ring, Susan M, Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R, Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J, Smith, Blair H, Smith, Jennifer A, Staessen, Jan A, Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D, Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, van Rooij, Frank JA, Venturini, Cristina, Vinkhuyzen, Anna AE, Völker, Uwe, Völzke, Henry, Vonk, Judith M, Vozzi, Diego, Waage, Johannes, Ware, Erin B, Willemsen, Gonneke, Attia, John R, Bennett, David A, Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Boomsma, Dorret I, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F, Cucca, Francesco, Cusi, Daniele, Deary, Ian J, Dedoussis, George V, van Duijn, Cornelia M, Eriksson, Johan G, Franke, Barbara, Franke, Lude, Gasparini, Paolo, Gejman, Pablo V, Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick JF, Gudnason, Vilmundur, van der Harst, Pim, Hayward, Caroline, Hinds, David A, Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G, Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon LR, Lehtimäki, Terho, Lehrer, Steven F, Magnusson, Patrik KE, Martin, Nicholas G, McGue, Matt, Metspalu, Andres, Pendleton, Neil, Penninx, Brenda WJH, Perola, Markus, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A, Samani, Nilesh J, Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild IA, Spector, Tim D, Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A Roy, Timpson, Nicholas J, Tiemeier, Henning, Tung, Joyce Y, Uitterlinden, André G, Vitart, Veronique, Vollenweider, Peter, Weir, David R, Wilson, James F, Wright, Alan F, Conley, Dalton C, Krueger, Robert F, Davey Smith, George, Hofman, Albert, Laibson, David I, Medland, Sarah E, Meyer, Michelle N, Yang, Jian, Johannesson, Magnus, Visscher, Peter M, Esko, Tõnu, Koellinger, Philipp D, Cesarini, David and Benjamin, Daniel J (2016) Genome-wide association study identifies 74 loci associated with educational attainment. Nature, 533 (7604). pp. 539-542. ISSN 0028-0836

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Abstract

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.