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

Nat Genet
Authors
Jeanne Savage
Philip Jansen
Sven Stringer
Kyoko Watanabe
Julien Bryois
Christiaan de Leeuw
Mats Nagel
Swapnil Awasthi
Peter Barr
Jonathan Coleman
Katrina Grasby
Anke Hammerschlag
Jakob Kaminski
Robert Karlsson
Eva Krapohl
Max Lam
Marianne Nygaard
Chandra Reynolds
Joey Trampush
Hannah Young
Delilah Zabaneh
Sara Hägg
Narelle Hansell
Ida Karlsson
Sten Linnarsson
Grant Montgomery
Ana Muñoz-Manchado
Erin Quinlan
Gunter Schumann
Nathan Skene
Bradley Webb
Tonya White
Dan Arking
Dimitrios Avramopoulos
Robert Bilder
Panos Bitsios
Katherine Burdick
Tyrone Cannon
Ornit Chiba-Falek
Andrea Christoforou
Elizabeth Cirulli
Eliza Congdon
Aiden Corvin
Gail Davies
Ian Deary
Pamela DeRosse
Dwight Dickinson
Srdjan Djurovic
Gary Donohoe
Emily Conley
Johan Eriksson
Thomas Espeseth
Nelson Freimer
Stella Giakoumaki
Ina Giegling
Michael Gill
David Glahn
Ahmad Hariri
Alex Hatzimanolis
Matthew Keller
Emma Knowles
Deborah Koltai
Bettina Konte
Jari Lahti
Stephanie Le Hellard
Todd Lencz
David Liewald
Edythe London
Astri Lundervold
Anil Malhotra
Ingrid Melle
Derek Morris
Anna Need
William Ollier
Aarno Palotie
Antony Payton
Neil Pendleton
Russell Poldrack
Katri Räikkönen
Ivar Reinvang
Panos Roussos
Dan Rujescu
Fred Sabb
Matthew Scult
Olav Smeland
Nikolaos Smyrnis
John Starr
Vidar Steen
Nikos Stefanis
Richard Straub
Kjetil Sundet
Henning Tiemeier
Aristotle Voineskos
Daniel Weinberger
Elisabeth Widén
Jin Yu
Goncalo Abecasis
Ole Andreassen
Gerome Breen
Lene Christiansen
Birgit Debrabant
Danielle Dick
Andreas Heinz
Jens Hjerling-Leffler
M Arfan Ikram
Kenneth Kendler
Nicholas Martin
Sarah Medland
Nancy Pedersen
Robert Plomin
Tinca Polderman
Stephan Ripke
Sophie van der Sluis
Patrick Sullivan
Scott Vrieze
Margaret Wright
Danielle Posthuma
Keywords
Female
Humans
Male
Genetic Predisposition to Disease
Middle Aged
Adolescent
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Brain
Intelligence
Abstract

Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence, 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.
Year of Publication
2018
Journal
Nat Genet
Volume
50
Issue
7
Pages
912-919
Date Published
2018 07
ISSN
1546-1718
DOI
10.1038/s41588-018-0152-6
PubMed ID
29942086
PubMed Central ID
PMC6411041
Links
Grant list
R01 AG049789 / AG / NIA NIH HHS / United States
R01 MH079800 / MH / NIMH NIH HHS / United States
P20 AA017828 / AA / NIAAA NIH HHS / United States
K01 MH098126 / MH / NIMH NIH HHS / United States
PL1 MH083271 / MH / NIMH NIH HHS / United States
L30 MH104879 / MH / NIMH NIH HHS / United States
R01 MH085772 / MH / NIMH NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R01 AG037985 / AG / NIA NIH HHS / United States
PL1 NS062410 / NS / NINDS NIH HHS / United States
G19/2 / MRC_ / Medical Research Council / United Kingdom
K23 MH077807 / MH / NIMH NIH HHS / United States
R01 MH092515 / MH / NIMH NIH HHS / United States
G0600237 / MRC_ / Medical Research Council / United Kingdom
R01 MH080912 / MH / NIMH NIH HHS / United States
R01 DA033369 / DA / NIDA NIH HHS / United States
K01 MH085812 / MH / NIMH NIH HHS / United States
R01 MH085018 / MH / NIMH NIH HHS / United States
RL1 MH083269 / MH / NIMH NIH HHS / United States
UL1 DE019580 / DE / NIDCR NIH HHS / United States
R01 AG028555 / AG / NIA NIH HHS / United States
R01 HG008983 / HG / NHGRI NIH HHS / United States
U54 EB020403 / EB / NIBIB NIH HHS / United States
UL1 RR031990 / RR / NCRR NIH HHS / United States
R03 AG045633 / AG / NIA NIH HHS / United States
P50 AA022537 / AA / NIAAA NIH HHS / United States
K02 AA018755 / AA / NIAAA NIH HHS / United States
P50 MH080173 / MH / NIMH NIH HHS / United States
P01 AG008761 / AG / NIA NIH HHS / United States
R37 AA011408 / AA / NIAAA NIH HHS / United States
R01 DA037904 / DA / NIDA NIH HHS / United States
R01 AA023974 / AA / NIAAA NIH HHS / United States
S10 OD018164 / OD / NIH HHS / United States
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
G0100594 / MRC_ / Medical Research Council / United Kingdom
R01 AG010175 / AG / NIA NIH HHS / United States
RL1 DA024853 / DA / NIDA NIH HHS / United States
BB/F022441/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
G0901461 / MRC_ / Medical Research Council / United Kingdom

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