@article {9877, title = {Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence}, journal = {Nature Genetics}, volume = {50}, year = {2018}, month = {Jan-07-2018}, pages = {912 - 919}, abstract = {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{\textquoteright}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. }, keywords = {Genome-Wide Association Study, Intelligence, Meta-analyses}, issn = {1061-4036}, doi = {10.1038/s41588-018-0152-6}, url = {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}, author = {Savage, Jeanne E. and Philip R Jansen and Stringer, Sven and Watanabe, Kyoko and Bryois, Julien and Christiaan de Leeuw and Nagel, Mats and Awasthi, Swapnil and Barr, Peter B. and Coleman, Jonathan R. I. and Grasby, Katrina L. and Anke R Hammerschlag and Kaminski, Jakob A. and Karlsson, Robert and Krapohl, Eva and Lam, Max and Nygaard, Marianne and Chandra A Reynolds and Joey W Trampush and Young, Hannah and Zabaneh, Delilah and H{\"a}gg, Sara and Narelle K Hansell and Ida Karlsson and Linnarsson, Sten and Grant W Montgomery and Mu{\~n}oz-Manchado, Ana B. and Quinlan, Erin B. and Schumann, Gunter and Skene, Nathan G. and Webb, Bradley T. and White, Tonya and Dan E Arking and Avramopoulos, Dimitrios and Robert M Bilder and Bitsios, Panos and Katherine E Burdick and Tyrone D. Cannon and Chiba-Falek, Ornit and Christoforou, Andrea and Elizabeth T. Cirulli and Congdon, Eliza and Corvin, Aiden and Gail Davies and Ian J Deary and DeRosse, Pamela and Dickinson, Dwight and Djurovic, Srdjan and Donohoe, Gary and Conley, Emily Drabant and Johan G Eriksson and Espeseth, Thomas and Nelson A. Freimer and Giakoumaki, Stella and Giegling, Ina and Gill, Michael and David C. Glahn and Ahmad R Hariri and Hatzimanolis, Alex and Matthew C Keller and Knowles, Emma and Koltai, Deborah and Konte, Bettina and Lahti, Jari and Stephanie Le Hellard and Lencz, Todd and David C Liewald and London, Edythe and Astri J Lundervold and Anil K. Malhotra and Melle, Ingrid and Morris, Derek and Anna C Need and William E R Ollier and Aarno Palotie and Payton, Antony and Pendleton, Neil and Russell A Poldrack and Katri R{\"a}ikk{\"o}nen and Reinvang, Ivar and Roussos, Panos and Rujescu, Dan and Fred W Sabb and Matthew A Scult and Smeland, Olav B. and Smyrnis, Nikolaos and John M Starr and Vidar M Steen and Nikos C Stefanis and Richard E Straub and Sundet, Kjetil and Henning Tiemeier and Aristotle N Voineskos and Daniel R Weinberger and Elisabeth Widen and Yu, Jin and Gon{\c c}alo R Abecasis and Andreassen, Ole A. and Breen, Gerome and Christiansen, Lene and Debrabant, Birgit and Danielle M. Dick and Heinz, Andreas and Hjerling-Leffler, Jens and Mohammed Arfan Ikram and Kendler, Kenneth S. and Nicholas G Martin and Sarah E Medland and Nancy L Pedersen and Plomin, Robert and Tinca J Polderman and Ripke, Stephan and van der Sluis, Sophie and Patrick F. Sullivan and Scott Vrieze and Margaret J Wright and Posthuma, Danielle} }