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

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

Nat Genet 2018 07 25;50(7):912-919. Epub 2018 Jun 25.

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-018-0152-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411041PMC
July 2018
48 Reads
2 Citations
29.352 Impact Factor

Publication Analysis

Top Keywords

genomic loci
8
genetic
5
intelligence
5
analysis find
4
find enrichment
4
intelligence alzheimer's
4
association analysis
4
interaction mapping
4
gene-based association
4
mapping gene-based
4
enrichment genetic
4
protective effects
4
coding regions
4
analysis protective
4
conserved coding
4
effects conserved
4
genetic effects
4
effects intelligence
4
chromatin interaction
4
mapping chromatin
4

References

(Supplied by CrossRef)

TJ Polderman et al.
Nat. Genet. 2015

C Wraw et al.
Intelligence 2015

G Davies et al.
Mol. Psychiatry 2015

G Davies et al.
Mol. Psychiatry 2016

S Sniekers et al.
Nat. Genet. 2017

JW Trampush et al.
Mol. Psychiatry 2017

D Zabaneh et al.
Mol. Psychiatry 2018

JB Carroll et al.
1993

C Spearman et al.
Am. J. Psychol. 1904

R Plomin et al.
Psychol. Bull. 2005

Similar Publications