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.

VL - 50 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30038396?dopt=Abstract ER - TY - JOUR T1 - Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. JF - Nat Genet Y1 - 2016 A1 - Okbay, Aysu A1 - Baselmans, Bart M L A1 - De Neve, Jan-Emmanuel A1 - Turley, Patrick A1 - Nivard, Michel G A1 - Mark Alan Fontana A1 - Meddens, S Fleur W A1 - Richard Karlsson Linnér A1 - Cornelius A Rietveld A1 - Derringer, Jaime A1 - Gratten, Jacob A1 - Lee, James J A1 - Liu, Jimmy Z A1 - de Vlaming, Ronald A1 - Ahluwalia, Tarunveer S A1 - Buchwald, Jadwiga A1 - Cavadino, Alana A1 - Frazier-Wood, Alexis C A1 - Furlotte, Nicholas A A1 - Garfield, Victoria A1 - Geisel, Marie Henrike A1 - Gonzalez, Juan R A1 - Haitjema, Saskia A1 - Karlsson, Robert A1 - van der Laan, Sander W A1 - Ladwig, Karl-Heinz A1 - J. Lahti A1 - Sven J van der Lee A1 - Penelope A Lind A1 - Tian Liu A1 - Lindsay K Matteson A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Minica, Camelia C A1 - Ilja M Nolte A1 - Dennis O Mook-Kanamori A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rawal, Rajesh A1 - Realo, Anu A1 - Rueedi, Rico A1 - Schmidt, Börge A1 - Albert Vernon Smith A1 - Stergiakouli, Evie A1 - Toshiko Tanaka A1 - Kent D Taylor A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Willems, Sara M A1 - Wei Zhao A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Patricia A. Boyle A1 - Cherney, Samantha A1 - Cox, Simon R A1 - Gail Davies A1 - Davis, Oliver S P A1 - Ding, Jun A1 - Nese Direk A1 - Eibich, Peter A1 - Emeny, Rebecca T A1 - Fatemifar, Ghazaleh A1 - Jessica D Faul A1 - Luigi Ferrucci A1 - Andreas J Forstner A1 - Gieger, Christian A1 - Gupta, Richa A1 - Tamara B Harris A1 - Harris, Juliette M A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Philip L. De Jager A1 - Marika A Kaakinen A1 - Kajantie, Eero A1 - Karhunen, Ville A1 - Kolcic, Ivana A1 - Kumari, Meena A1 - Lenore J Launer A1 - Lude L Franke A1 - Li-Gao, Ruifang A1 - Koini, Marisa A1 - Loukola, Anu A1 - Marques-Vidal, Pedro A1 - Grant W Montgomery A1 - Mosing, Miriam A A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Petrovic, Katja E A1 - Pulkki-Raback, Laura A1 - Quaye, Lydia A1 - Katri Räikkönen A1 - Rudan, Igor A1 - Rodney J Scott A1 - Jennifer A Smith A1 - Angelina R Sutin A1 - Trzaskowski, Maciej A1 - Anna A E Vinkhuyzen A1 - Lei Yu A1 - Zabaneh, Delilah A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Dorret I Boomsma A1 - Snieder, Harold A1 - Chang, Shun-Chiao A1 - Francesco Cucca A1 - Ian J Deary A1 - Cornelia M van Duijn A1 - Johan G. Eriksson A1 - Bültmann, Ute A1 - Eco J. C. de Geus A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - Hansen, Torben A1 - Catharina A Hartman A1 - Haworth, Claire M A A1 - Caroline Hayward A1 - Heath, Andrew C A1 - Hinds, David A A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Keltikangas-Järvinen, Liisa A1 - Kraft, Peter A1 - Laura D Kubzansky A1 - Lehtimäki, Terho A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Melinda C Mills A1 - de Mutsert, Renée A1 - Oldehinkel, Albertine J A1 - Pasterkamp, Gerard A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Polasek, Ozren A1 - Power, Christine A1 - Rich, Stephen S A1 - Rosendaal, Frits R A1 - Hester M. den Ruijter A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Svento, Rauli A1 - Schmidt, Reinhold A1 - Alizadeh, Behrooz Z A1 - Thorkild I. A. Sørensen A1 - Tim D Spector A1 - Steptoe, Andrew A1 - Antonio Terracciano A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - André G Uitterlinden A1 - Vollenweider, Peter A1 - Wagner, Gert G A1 - David R Weir A1 - Yang, Jian A1 - Dalton C Conley A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Pickrell, Joseph K A1 - Tõnu Esko A1 - Krueger, Robert F A1 - Jonathan P. Beauchamp A1 - Philipp D Koellinger A1 - Daniel J. Benjamin A1 - Bartels, Meike A1 - Cesarini, David KW - Anxiety Disorders KW - Bayes Theorem KW - depression KW - Genome-Wide Association Study KW - Humans KW - Neuroticism KW - Phenotype KW - Polymorphism, Single Nucleotide AB -Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

VL - 48 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract ER -