RT Journal Article
SR Electronic
T1 GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 184853
DO 10.1101/184853
A1 Jeanne E Savage
A1 Philip R Jansen
A1 Sven Stringer
A1 Kyoko Watanabe
A1 Julien Bryois
A1 Christiaan A de Leeuw
A1 Mats Nagel
A1 Swapnil Awasthi
A1 Peter B Barr
A1 Jonathan R I Coleman
A1 Katrina L Grasby
A1 Anke R Hammerschlag
A1 Jakob Kaminski
A1 Robert Karlsson
A1 Eva Krapohl
A1 Max Lam
A1 Marianne Nygaard
A1 Chandra A Reynolds
A1 Joey W Trampush
A1 Hannah Young
A1 Delilah Zabaneh
A1 Sara Hägg
A1 Narelle K Hansell
A1 Ida K Karlsson
A1 Sten Linnarsson
A1 Grant W Montgomery
A1 Ana B Muñoz-Manchado
A1 Erin B Quinlan
A1 Gunter Schumann
A1 Nathan Skene
A1 Bradley T Webb
A1 Tonya White
A1 Dan E Arking
A1 Deborah K Attix
A1 Dimitrios Avramopoulos
A1 Robert M Bilder
A1 Panos Bitsios
A1 Katherine E Burdick
A1 Tyrone D Cannon
A1 Ornit Chiba-Falek
A1 Andrea Christoforou
A1 Elizabeth T Cirulli
A1 Eliza Congdon
A1 Aiden Corvin
A1 Gail Davies
A1 Ian J Deary
A1 Pamela DeRosse
A1 Dwight Dickinson
A1 Srdjan Djurovic
A1 Gary Donohoe
A1 Emily Drabant Conley
A1 Johan G Eriksson
A1 Thomas Espeseth
A1 Nelson A Freimer
A1 Stella Giakoumaki
A1 Ina Giegling
A1 Michael Gill
A1 David C Glahn
A1 Ahmad R Hariri
A1 Alex Hatzimanolis
A1 Matthew C Keller
A1 Emma Knowles
A1 Bettina Konte
A1 Jari Lahti
A1 Stephanie Le Hellard
A1 Todd Lencz
A1 David C Liewald
A1 Edythe London
A1 Astri J Lundervold
A1 Anil K Malhotra
A1 Ingrid Melle
A1 Derek Morris
A1 Anna C Need
A1 William Ollier
A1 Aarno Palotie
A1 Antony Payton
A1 Neil Pendleton
A1 Russell A Poldrack
A1 Katri Räikkönen
A1 Ivar Reinvang
A1 Panos Roussos
A1 Dan Rujescu
A1 Fred W Sabb
A1 Matthew A Scult
A1 Olav B Smeland
A1 Nikolaos Smyrnis
A1 John M Starr
A1 Vidar M Steen
A1 Nikos C Stefanis
A1 Richard E Straub
A1 Kjetil Sundet
A1 Aristotle N Voineskos
A1 Daniel R Weinberger
A1 Elisabeth Widen
A1 Jin Yu
A1 Goncalo Abecasis
A1 Ole A Andreassen
A1 Gerome Breen
A1 Lene Christiansen
A1 Birgit Debrabant
A1 Danielle M Dick
A1 Andreas Heinz
A1 Jens Hjerling-Leffler
A1 M Arfan Ikram
A1 Kenneth S Kendler
A1 Nicholas G Martin
A1 Sarah E Medland
A1 Nancy L Pedersen
A1 Robert Plomin
A1 Tinca JC Polderman
A1 Stephan Ripke
A1 Sophie van der Sluis
A1 Patrick F Sullivan
A1 Henning Tiemeier
A1 Scott I Vrieze
A1 Margaret J Wright
A1 Danielle Posthuma
YR 2017
UL http://biorxiv.org/content/early/2017/09/06/184853.abstract
AB 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 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.