TY - JOUR T1 - Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence JF - Nature Genetics Y1 - 2018 A1 - Savage, Jeanne E. A1 - Philip R Jansen A1 - Stringer, Sven A1 - Watanabe, Kyoko A1 - Bryois, Julien A1 - Christiaan de Leeuw A1 - Nagel, Mats A1 - Awasthi, Swapnil A1 - Barr, Peter B. A1 - Coleman, Jonathan R. I. A1 - Grasby, Katrina L. A1 - Anke R Hammerschlag A1 - Kaminski, Jakob A. A1 - Karlsson, Robert A1 - Krapohl, Eva A1 - Lam, Max A1 - Nygaard, Marianne A1 - Chandra A Reynolds A1 - Joey W Trampush A1 - Young, Hannah A1 - Zabaneh, Delilah A1 - Hägg, Sara A1 - Narelle K Hansell A1 - Ida Karlsson A1 - Linnarsson, Sten A1 - Grant W Montgomery A1 - Muñoz-Manchado, Ana B. A1 - Quinlan, Erin B. A1 - Schumann, Gunter A1 - Skene, Nathan G. A1 - Webb, Bradley T. A1 - White, Tonya A1 - Dan E Arking A1 - Avramopoulos, Dimitrios A1 - Robert M Bilder A1 - Bitsios, Panos A1 - Katherine E Burdick A1 - Tyrone D. Cannon A1 - Chiba-Falek, Ornit A1 - Christoforou, Andrea A1 - Elizabeth T. Cirulli A1 - Congdon, Eliza A1 - Corvin, Aiden A1 - Gail Davies A1 - Ian J Deary A1 - DeRosse, Pamela A1 - Dickinson, Dwight A1 - Djurovic, Srdjan A1 - Donohoe, Gary A1 - Conley, Emily Drabant A1 - Johan G Eriksson A1 - Espeseth, Thomas A1 - Nelson A. Freimer A1 - Giakoumaki, Stella A1 - Giegling, Ina A1 - Gill, Michael A1 - David C. Glahn A1 - Ahmad R Hariri A1 - Hatzimanolis, Alex A1 - Matthew C Keller A1 - Knowles, Emma A1 - Koltai, Deborah A1 - Konte, Bettina A1 - Lahti, Jari A1 - Stephanie Le Hellard A1 - Lencz, Todd A1 - David C Liewald A1 - London, Edythe A1 - Astri J Lundervold A1 - Anil K. Malhotra A1 - Melle, Ingrid A1 - Morris, Derek A1 - Anna C Need A1 - William E R Ollier A1 - Aarno Palotie A1 - Payton, Antony A1 - Pendleton, Neil A1 - Russell A Poldrack A1 - Katri Räikkönen A1 - Reinvang, Ivar A1 - Roussos, Panos A1 - Rujescu, Dan A1 - Fred W Sabb A1 - Matthew A Scult A1 - Smeland, Olav B. A1 - Smyrnis, Nikolaos A1 - John M Starr A1 - Vidar M Steen A1 - Nikos C Stefanis A1 - Richard E Straub A1 - Sundet, Kjetil A1 - Henning Tiemeier A1 - Aristotle N Voineskos A1 - Daniel R Weinberger A1 - Elisabeth Widen A1 - Yu, Jin A1 - Gonçalo R Abecasis A1 - Andreassen, Ole A. A1 - Breen, Gerome A1 - Christiansen, Lene A1 - Debrabant, Birgit A1 - Danielle M. Dick A1 - Heinz, Andreas A1 - Hjerling-Leffler, Jens A1 - Mohammed Arfan Ikram A1 - Kendler, Kenneth S. A1 - Nicholas G Martin A1 - Sarah E Medland A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Tinca J Polderman A1 - Ripke, Stephan A1 - van der Sluis, Sophie A1 - Patrick F. Sullivan A1 - Scott Vrieze A1 - Margaret J Wright A1 - Posthuma, Danielle KW - Genome-Wide Association Study KW - Intelligence KW - Meta-analyses AB - Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. VL - 50 UR - http://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdfhttp://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdf IS - 7 JO - Nat Genet ER -