| Title: |
Genome-wide association meta-analysis in 269,867 individuals identifies new genetic 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 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 |
| Contributors: |
Research Programs Unit; CAMM - Research Program for Clinical and Molecular Metabolism; 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 |
| Publisher Information: |
Nature Research |
| Publication Year: |
2019 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
GENERAL COGNITIVE FUNCTION; EDUCATIONAL-ATTAINMENT; TEST BATTERIES; GWAS; TRAITS; RISK; LOCI; HERITABILITY; ANNOTATION; CONSORTIUM; Biomedicine |
| Description: |
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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISBN: |
978-85-04-89434-9; 85-04-89434-7 |
| Relation: |
This work was funded by the Netherlands Organization for Scientific Research through the following grants: NWO Brain and Cognition 433-09-228 (D.P.), NWO MagW VIDI 452-12-014 (S.v.d.S.), NWO VICI 453-13-005 (D.P.), and 645-000-003 (D.P.). P.R.J. was funded by the Sophia Foundation for Scientific Research (SSWO, grant S14-27 to P.R.J.). The analyses were carried out on the Genetic Cluster Computer, which is financed by the Netherlands Scientific Organization (NWO: 480-05-003 to D.P.), Vrije Universiteit, Amsterdam, The Netherlands, and the Dutch Brain Foundation, and is hosted by the Dutch National Computing and Networking Services, SurfSARA. J.H.-L. was funded by the Swedish Research Council (Vetenskapsradet, award 20143863), StratNeuro, the Wellcome Trust (108726/Z/15/Z), and the Swedish Brain Foundation (Hjarnfonden). N.G.S. was supported by the Wellcome Trust (108726/Z/15/Z). J.B. was funded by the Swiss National Science Foundation. This research has been conducted using the UK Biobank resource under application 16406. We thank the numerous participants, researchers, and staff from many studies who collected and contributed to the data. Additional acknowledgements can be found in the Supplementary Information.; https://hdl.handle.net/10138/303673; 85048943479; 000437224400005 |
| Availability: |
https://hdl.handle.net/10138/303673 |
| Rights: |
info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.2C0CCB22 |
| Database: |
BASE |