Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

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

Publication ,  Journal Article
Savage, JE; Jansen, PR; Stringer, S; Watanabe, K; Bryois, J; de Leeuw, CA; Nagel, M; Awasthi, S; Barr, PB; Coleman, JRI; Grasby, KL; Lam, M ...
Published in: Nat Genet
July 2018

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

July 2018

Volume

50

Issue

7

Start / End Page

912 / 919

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Intelligence
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., de Leeuw, C. A., … Posthuma, D. (2018). Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat Genet, 50(7), 912–919. https://doi.org/10.1038/s41588-018-0152-6
Savage, Jeanne E., Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois, Christiaan A. de Leeuw, Mats Nagel, et al. “Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.Nat Genet 50, no. 7 (July 2018): 912–19. https://doi.org/10.1038/s41588-018-0152-6.
Savage JE, Jansen PR, Stringer S, Watanabe K, Bryois J, de Leeuw CA, et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat Genet. 2018 Jul;50(7):912–9.
Savage, Jeanne E., et al. “Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.Nat Genet, vol. 50, no. 7, July 2018, pp. 912–19. Pubmed, doi:10.1038/s41588-018-0152-6.
Savage 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 ED, 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, Widen E, Yu J, Abecasis G, Andreassen OA, Breen G, Christiansen L, Debrabant B, Dick DM, Heinz A, Hjerling-Leffler J, Ikram MA, 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. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat Genet. 2018 Jul;50(7):912–919.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

July 2018

Volume

50

Issue

7

Start / End Page

912 / 919

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Intelligence
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Developmental Biology