Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
James J LeeRobbee WedowAysu OkbayEdward KongOmeed MaghzianMeghan ZacherTuan Anh Nguyen-VietPeter BowersJulia SidorenkoRichard Karlsson LinnérMark Alan FontanaTushar KunduChanwook LeeHui LiRuoxi LiRebecca RoyerPascal N TimshelRaymond K WaltersEmily A WilloughbyLoïc Yengonull nullnull nullnull nullMaris AlverYanchun BaoDavid W ClarkFelix R DayNicholas A FurlottePeter K JoshiKathryn E KemperAaron KleinmanClaudia LangenbergReedik MägiJoey W TrampushShefali Setia VermaYang WuMax LamJing Hua ZhaoZhili ZhengJason D BoardmanHarry CampbellJeremy FreeseKathleen Mullan HarrisCaroline HaywardPamela HerdMeena KumariTodd LenczJian'an LuanAnil K MalhotraAndres MetspaluLili A MilaniKen K OngJohn R B PerryDavid J PorteousMarylyn DeRiggi RitchieMelissa C SmartBlair Hamilton SmithJoyce Y TungNicholas J WarehamJames F WilsonJonathan P BeauchampDalton C ConleyTõnu EskoSteven F LehrerPatrik K E MagnussonSven OskarssonTune H PersMatthew R RobinsonKevin ThomChelsea WatsonChristopher F ChabrisMichelle N MeyerDavid I LaibsonJian YangMagnus JohannessonPhilipp D KoellingerPatrick TurleyPeter M VisscherDaniel J BenjaminDavid CesariniPublished in: Nature genetics (2018)
Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.