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Nat Genet DOI:10.1038/s41588-018-0152-6

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

Publication TypeJournal Article
Year of Publication2018
AuthorsSavage, JE, Jansen, PR, Stringer, S, Watanabe, K, Bryois, J, de Leeuw, CA, Nagel, M, Awasthi, S, Barr, PB, Coleman, JRI, Grasby, KL, Hammerschlag, AR, Kaminski, JA, Karlsson, R, Krapohl, E, Lam, M, Nygaard, M, Reynolds, CA, Trampush, JW, Young, H, Zabaneh, D, Hägg, S, Hansell, NK, Karlsson, IK, Linnarsson, S, Montgomery, GW, Muñoz-Manchado, AB, Quinlan, EB, Schumann, G, Skene, NG, Webb, BT, White, T, Arking, DE, Avramopoulos, D, Bilder, RM, Bitsios, P, Burdick, KE, Cannon, TD, Chiba-Falek, O, Christoforou, A, Cirulli, ET, Congdon, E, Corvin, A, Davies, G, Deary, IJ, DeRosse, P, Dickinson, D, Djurovic, S, Donohoe, G, Conley, EDrabant, Eriksson, JG, Espeseth, T, Freimer, NA, Giakoumaki, S, Giegling, I, Gill, M, Glahn, DC, Hariri, AR, Hatzimanolis, A, Keller, MC, Knowles, E, Koltai, D, Konte, B, Lahti, J, Le Hellard, S, Lencz, T, Liewald, DC, London, E, Lundervold, AJ, Malhotra, AK, Melle, I, Morris, D, Need, AC, Ollier, W, Palotie, A, Payton, A, Pendleton, N, Poldrack, RA, Räikkönen, K, Reinvang, I, Roussos, P, Rujescu, D, Sabb, FW, Scult, MA, Smeland, OB, Smyrnis, N, Starr, JM, Steen, VM, Stefanis, NC, Straub, RE, Sundet, K, Tiemeier, H, Voineskos, AN, Weinberger, DR, Widén, E, Yu, J, Abecasis, G, Andreassen, OA, Breen, G, Christiansen, L, Debrabant, B, Dick, DM, Heinz, A, Hjerling-Leffler, J, M Ikram, A, Kendler, KS, Martin, NG, Medland, SE, Pedersen, NL, Plomin, R, Polderman, TJC, Ripke, S, van der Sluis, S, Sullivan, PF, Vrieze, SI, Wright, MJ, Posthuma, D
JournalNat Genet
Volume50
Issue7
Pages912-919
Date Published2018 07
ISSN1546-1718
KeywordsAdolescent, Brain, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intelligence, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci
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.

DOI10.1038/s41588-018-0152-6
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29942086?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID29942086
PubMed Central IDPMC6411041
Grant ListR01 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
R01 DA033369 / DA / NIDA NIH HHS / United States
K01 MH085812 / MH / NIMH NIH HHS / United States
PL1 MH083271 / 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 MH085772 / MH / NIMH NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
R01 AG037985 / AG / NIA 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
PL1 NS062410 / NS / NINDS NIH HHS / United States
G19/2 / / Medical Research Council / United Kingdom
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
K23 MH077807 / MH / NIMH NIH HHS / United States
S10 OD018164 / OD / NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 MH092515 / MH / NIMH NIH HHS / United States
G0600237 / / Medical Research Council / United Kingdom
G0100594 / / Medical Research Council / United Kingdom
R01 AG010175 / AG / NIA NIH HHS / United States
RL1 DA024853 / DA / NIDA NIH HHS / United States
BB/F022441/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G0901461 / / Medical Research Council / United Kingdom
R01 MH080912 / MH / NIMH NIH HHS / United States