GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence
Authors: Savage Jeanne E , Jansen Philip R , Stringer Sven , Watanabe Kyoko , Bryois Julien , de Leeuw Christiaan A , Nagel Mats , Awasthi Swapnil , Barr Peter B , Coleman Jonathan R I , Grasby Katrina L , Hammerschlag Anke R , Kaminski Jakob , Karlsson Robert , Krapohl Eva , Lam Max , Nygaard Marianne , Reynolds Chandra A , Trampush Joey W , Young Hannah , Zabaneh Delilah , Hägg Sara , Hansell Narelle K , Karlsson Ida K , Linnarsson Sten , Montgomery Grant W , Muñoz-Manchado Ana B , Quinlan Erin B , Schumann Gunter , Skene Nathan , Webb Bradley T , White Tonya , Arking Dan E , Attix Deborah K , Avramopoulos Dimitrios , Bilder Robert M , Bitsios Panos , Burdick Katherine E , Cannon Tyrone D , Chiba-Falek Ornit , Christoforou Andrea , Cirulli Elizabeth T , Congdon Eliza , Corvin Aiden , Davies Gail , Deary Ian J , DeRosse Pamela , Dickinson Dwight , Djurovic Srdjan , Donohoe Gary , Conley Emily Drabant , Eriksson Johan G , Espeseth Thomas , Freimer Nelson A , Giakoumaki Stella , Giegling Ina , Gill Michael , Glahn David C , Hariri Ahmad R , Hatzimanolis Alex , Keller Matthew C , Knowles Emma , Konte Bettina , Lahti Jari , Hellard Stephanie Le , Lencz Todd , Liewald David C , London Edythe , Lundervold Astri J , Malhotra Anil K , Melle Ingrid , Morris Derek , Need Anna C , Ollier William , Palotie Aarno , Payton Antony , Pendleton Neil , Poldrack Russell A , Räikkönen Katri , Reinvang Ivar , Roussos Panos , Rujescu Dan , Sabb Fred W , Scult Matthew A , Smeland Olav B , Smyrnis Nikolaos , Starr John M , Steen Vidar M , Stefanis Nikos C , Straub Richard E , Sundet Kjetil , Voineskos Aristotle N , Weinberger Daniel R , Widen Elisabeth , Yu Jin , Abecasis Goncalo , Andreassen Ole A , Breen Gerome , Christiansen Lene , Debrabant Birgit , Dick Danielle M , Heinz Andreas , Hjerling-Leffler Jens , Ikram M Arfan , Kendler Kenneth S , Martin Nicholas G , Medland Sarah E , Pedersen Nancy L , Plomin Robert , Polderman Tinca JC , Ripke Stephan , Sluis Sophie van der , Sullivan Patrick F , Tiemeier Henning , Vrieze Scott I , Wright Margaret J , Posthuma Danielle 
Published: September 2017

Intelligence is highly heritable1and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence3–7, but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) 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 identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer’s dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.