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

Research output: Contribution to journalLetter

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 & 30 others 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

Original languageEnglish
Number of pages8
JournalNature Genetics
Early online date25 Jun 2018
DOIs
Publication statusPublished - Jul 2018

King's Authors

Abstract

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 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.

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