Genome-wide association study identifies 74 loci associated with educational attainment.
Genome-wide association study identifies 74 loci associated with educational attainment.
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DOI：
10.1038/nature17671
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发表时间：
2016-05-26
期刊：
影响因子：
64.8
通讯作者：
Benjamin DJ
中科院分区：
文献类型：
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作者：
Okbay A;Beauchamp JP;Fontana MA;Lee JJ;Pers TH;Rietveld CA;Turley P;Chen GB;Emilsson V;Meddens SF;Oskarsson S;Pickrell JK;Thom K;Timshel P;de Vlaming R;Abdellaoui A;Ahluwalia TS;Bacelis J;Baumbach C;Bjornsdottir G;Brandsma JH;Pina Concas M;Derringer J;Furlotte NA;Galesloot TE;Girotto G;Gupta R;Hall LM;Harris SE;Hofer E;Horikoshi M;Huffman JE;Kaasik K;Kalafati IP;Karlsson R;Kong A;Lahti J;van der Lee SJ;deLeeuw C;Lind PA;Lindgren KO;Liu T;Mangino M;Marten J;Mihailov E;Miller MB;van der Most PJ;Oldmeadow C;Payton A;Pervjakova N;Peyrot WJ;Qian Y;Raitakari O;Rueedi R;Salvi E;Schmidt B;Schraut KE;Shi J;Smith AV;Poot RA;St Pourcain B;Teumer A;Thorleifsson G;Verweij N;Vuckovic D;Wellmann J;Westra HJ;Yang J;Zhao W;Zhu Z;Alizadeh BZ;Amin N;Bakshi A;Baumeister SE;Biino G;Bønnelykke K;Boyle PA;Campbell H;Cappuccio FP;Davies G;De Neve JE;Deloukas P;Demuth I;Ding J;Eibich P;Eisele L;Eklund N;Evans DM;Faul JD;Feitosa MF;Forstner AJ;Gandin I;Gunnarsson B;Halldórsson BV;Harris TB;Heath AC;Hocking LJ;Holliday EG;Homuth G;Horan MA;Hottenga JJ;de Jager PL;Joshi PK;Jugessur A;Kaakinen MA;Kähönen M;Kanoni S;Keltigangas-Järvinen L;Kiemeney LA;Kolcic I;Koskinen S;Kraja AT;Kroh M;Kutalik Z;Latvala A;Launer LJ;Lebreton MP;Levinson DF;Lichtenstein P;Lichtner P;Liewald DC;LifeLines Cohort Study;Loukola A;Madden PA;Mägi R;Mäki-Opas T;Marioni RE;Marques-Vidal P;Meddens GA;McMahon G;Meisinger C;Meitinger T;Milaneschi Y;Milani L;Montgomery GW;Myhre R;Nelson CP;Nyholt DR;Ollier WE;Palotie A;Paternoster L;Pedersen NL;Petrovic KE;Porteous DJ;Räikkönen K;Ring SM;Robino A;Rostapshova O;Rudan I;Rustichini A;Salomaa V;Sanders AR;Sarin AP;Schmidt H;Scott RJ;Smith BH;Smith JA;Staessen JA;Steinhagen-Thiessen E;Strauch K;Terracciano A;Tobin MD;Ulivi S;Vaccargiu S;Quaye L;van Rooij FJ;Venturini C;Vinkhuyzen AA;Völker U;Völzke H;Vonk JM;Vozzi D;Waage J;Ware EB;Willemsen G;Attia JR;Bennett DA;Berger K;Bertram L;Bisgaard H;Boomsma DI;Borecki IB;Bültmann U;Chabris CF;Cucca F;Cusi D;Deary IJ;Dedoussis GV;van Duijn CM;Eriksson JG;Franke B;Franke L;Gasparini P;Gejman PV;Gieger C;Grabe HJ;Gratten J;Groenen PJ;Gudnason V;van der Harst P;Hayward C;Hinds DA;Hoffmann W;Hyppönen E;Iacono WG;Jacobsson B;Järvelin MR;Jöckel KH;Kaprio J;Kardia SL;Lehtimäki T;Lehrer SF;Magnusson PK;Martin NG;McGue M;Metspalu A;Pendleton N;Penninx BW;Perola M;Pirastu N;Pirastu M;Polasek O;Posthuma D;Power C;Province MA;Samani NJ;Schlessinger D;Schmidt R;Sørensen TI;Spector TD;Stefansson K;Thorsteinsdottir U;Thurik AR;Timpson NJ;Tiemeier H;Tung JY;Uitterlinden AG;Vitart V;Vollenweider P;Weir DR;Wilson JF;Wright AF;Conley DC;Krueger RF;Davey Smith G;Hofman A;Laibson DI;Medland SE;Meyer MN;Yang J;Johannesson M;Visscher PM;Esko T;Koellinger PD;Cesarini D;Benjamin DJ
受教育程度（EA）受到社交及其他环境因素的强烈影响，但遗传因素也估计占个体差异的至少20%。我们报告了EA的全基因组关联研究（GWAS）的结果，该研究将我们早期发现的101，069个个体的样本扩展到293，723个个体，并在来自英国生物银行的111，349个个体的独立样本中进行了复制。我们现在确定了74个全基因组显著位点与完成的教育年限相关。与教育程度相关的单核苷酸多态性（SNP）在调节胎儿大脑基因表达的基因组区域中不成比例地发现。候选基因优先在神经组织中表达，特别是在产前期间，并富集参与神经发育的生物学途径。我们的研究结果表明，即使对于主要由环境决定的行为表型，一个强大的GWAS也能识别出可复制的相关遗传变异，这些变异表明了生物学相关的途径。由于EA是在大量的个人测量，它将继续是有用的代理表型在努力表征相关表型，包括认知和神经精神疾病的遗传影响。
Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) 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 behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA 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 disease.