Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

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Savage , J E , Jansen , P R , Stringer , S , Watanabe , K , Bryois , J , de Leeuw , C A , Nagel , M , Awasthi , S , Barr , P B , Coleman , J R I , Grasby , K L , Hammerschlag , A R , Kaminski , J A , Karlsson , R , Krapohl , E , Lam , M , Nygaard , M , Reynolds , C A , Trampush , J W , Young , H , Zabaneh , D , Hagg , S , Hansell , N K , Karlsson , I K , Linnarsson , S , Montgomery , G W , Munoz-Manchado , A B , Quinlan , E B , Schumann , G , Skene , N G , Webb , B T , White , T , Arking , D E , Avramopoulos , D , Bilder , R M , Bitsios , P , Burdick , K E , Cannon , T D , Chiba-Falek , O , Christoforou , A , Cirulli , E T , Congdon , E , Corvin , A , Davies , G , Deary , I J , DeRosse , P , Dickinson , D , Djurovic , S , Donohoe , G , Conley , E D , Eriksson , J G , Espeseth , T , Freimer , N A , Giakoumaki , S , Giegling , I , Gill , M , Glahn , D C , Hariri , A R , Hatzimanolis , A , Keller , M C , Knowles , E , Koltai , D , Konte , B , Lahti , J , Le Hellard , S , Lencz , T , Liewald , D C , London , E , Lundervold , A J , Malhotra , A K , Melle , I , Morris , D , Need , A C , Ollier , W , Palotie , A , Payton , A , Pendleton , N , Poldrack , R A , Räikkönen , K , Reinvang , I , Roussos , P , Rujescu , D , Sabb , F W , Scult , M A , Smeland , O B , Smyrnis , N , Starr , J M , Steen , V M , Stefanis , N C , Straub , R E , Sundet , K , Tiemeier , H , Voineskos , A N , Weinberger , D R , Widen , E , Yu , J , Abecasis , G , Andreassen , O A , Breen , G , Christiansen , L , Debrabant , B , Dick , D M , Heinz , A , Hjerling-Leffler , J , Ikram , M A , Kendler , K S , Martin , N G , Medland , S E , Pedersen , N L , Plomin , R , Polderman , T J C , Ripke , S , van der Sluis , S , Sullivan , P F , Vrieze , S I , Wright , M J & Posthuma , D 2018 , ' Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence ' , Nature Genetics , vol. 50 , no. 7 , pp. 912-+ . https://doi.org/10.1038/s41588-018-0152-6

Title: Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
Author: 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 A.; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A.; Trampush, Joey W.; Young, Hannah; Zabaneh, Delilah; Hagg, Sara; Hansell, Narelle K.; Karlsson, Ida K.; Linnarsson, Sten; Montgomery, Grant W.; Munoz-Manchado, Ana B.; Quinlan, Erin B.; Schumann, Gunter; Skene, Nathan G.; Webb, Bradley T.; White, Tonya; Arking, Dan E.; 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; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; 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; Tiemeier, Henning; 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 J. C.; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F.; Vrieze, Scott I.; Wright, Margaret J.; Posthuma, Danielle
Contributor organization: Research Programs Unit
Diabetes and Obesity Research Program
Department of General Practice and Primary Health Care
Johan Eriksson / Principal Investigator
Clinicum
University of Helsinki
Medicum
Helsinki Collegium for Advanced Studies
Department of Psychology and Logopedics
Centre of Excellence in Complex Disease Genetics
Aarno Palotie / Principal Investigator
Institute for Molecular Medicine Finland
Elisabeth Ingrid Maria Widen / Principal Investigator
Developmental Psychology Research Group
Genomics of Neurological and Neuropsychiatric Disorders
Genomic Discoveries and Clinical Translation
Date: 2018-07
Language: eng
Number of pages: 11
Belongs to series: Nature Genetics
ISSN: 1061-4036
DOI: https://doi.org/10.1038/s41588-018-0152-6
URI: http://hdl.handle.net/10138/303673
Abstract: Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). 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.
Subject: GENERAL COGNITIVE FUNCTION
EDUCATIONAL-ATTAINMENT
TEST BATTERIES
GWAS
TRAITS
RISK
LOCI
HERITABILITY
ANNOTATION
CONSORTIUM
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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