| Literature DB >> 29942086 |
Jeanne E Savage1, Philip R Jansen1,2, Sven Stringer1, Kyoko Watanabe1, Julien Bryois3, Christiaan A de Leeuw1, Mats Nagel4, Swapnil Awasthi5, Peter B Barr6, Jonathan R I Coleman7,8, Katrina L Grasby9, Anke R Hammerschlag1, Jakob A Kaminski5,10, Robert Karlsson3, Eva Krapohl7, Max Lam11, Marianne Nygaard12,13, Chandra A Reynolds14, Joey W Trampush15,16, Hannah Young17, Delilah Zabaneh7, Sara Hägg3, Narelle K Hansell18, Ida K Karlsson3, Sten Linnarsson19, Grant W Montgomery9,20, Ana B Muñoz-Manchado19, Erin B Quinlan21, Gunter Schumann21, Nathan G Skene19,22, Bradley T Webb23,24, Tonya White2, Dan E Arking25, Dimitrios Avramopoulos25,26, Robert M Bilder27, Panos Bitsios28, Katherine E Burdick29,30,31, Tyrone D Cannon32, Ornit Chiba-Falek33, Andrea Christoforou34, Elizabeth T Cirulli35, Eliza Congdon27, Aiden Corvin36, Gail Davies37,38, Ian J Deary37,38, Pamela DeRosse39,40,41, Dwight Dickinson42, Srdjan Djurovic43,44, Gary Donohoe45, Emily Drabant Conley46, Johan G Eriksson47, Thomas Espeseth48,49, Nelson A Freimer27, Stella Giakoumaki50, Ina Giegling51, Michael Gill36, David C Glahn52, Ahmad R Hariri53, Alex Hatzimanolis54,55,56, Matthew C Keller57, Emma Knowles52, Deborah Koltai58, Bettina Konte51, Jari Lahti59,60, Stephanie Le Hellard34,44, Todd Lencz39,40,41, David C Liewald38, Edythe London27,61, Astri J Lundervold62,63, Anil K Malhotra39,40,41, Ingrid Melle44,49, Derek Morris45, Anna C Need64, William Ollier65, Aarno Palotie66,67,68, Antony Payton69, Neil Pendleton70, Russell A Poldrack71, Katri Räikkönen72, Ivar Reinvang48, Panos Roussos29,30,73, Dan Rujescu51, Fred W Sabb74, Matthew A Scult53, Olav B Smeland75, Nikolaos Smyrnis54,55, John M Starr37,76, Vidar M Steen34,44, Nikos C Stefanis54,55,56, Richard E Straub77, Kjetil Sundet48,49, Henning Tiemeier2,78, Aristotle N Voineskos79, Daniel R Weinberger77, Elisabeth Widen66, Jin Yu39, Goncalo Abecasis80,81, Ole A Andreassen49,75,82, Gerome Breen7,8, Lene Christiansen12,13, Birgit Debrabant13, Danielle M Dick6,83,84, Andreas Heinz5, Jens Hjerling-Leffler19, M Arfan Ikram78, Kenneth S Kendler23,24,83, Nicholas G Martin9, Sarah E Medland9, Nancy L Pedersen3, Robert Plomin7, Tinca J C Polderman1, Stephan Ripke5,85,86, Sophie van der Sluis4, Patrick F Sullivan3,87, Scott I Vrieze17, Margaret J Wright18,88, Danielle Posthuma89,90.
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'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.Entities:
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Year: 2018 PMID： 29942086 PMCID： PMC6411041 DOI： 10.1038/s41588-018-0152-6
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330