Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Suzanne Sniekers, Sven Stringer, Kyoko Watanabe, Philip R Jansen, Jonathan R I Coleman, Eva Krapohl, Erdogan Taskesen, Anke R Hammerschlag, Aysu Okbay, Delilah Zabaneh, Najaf Amin, Gerome Breen, David Cesarini, Christopher F Chabris, William G Iacono, M Arfan Ikram, Magnus Johannesson, Philipp Koellinger, James J Lee, Patrik K E MagnussonMatt McGue, Mike B Miller, William E R Ollier, Antony Payton, Neil Pendleton, Robert Plomin, Cornelius A Rietveld, Henning Tiemeier, Cornelia M van Duijn, Danielle Posthuma

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Abstract

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

Original languageEnglish
Pages (from-to)1107-1112
Number of pages6
JournalNature Genetics
Volume49
Issue number7
Early online date22 May 2017
DOIs
Publication statusPublished - 1 Jul 2017

Funding

FundersFunder number
National Institute on Drug AbuseR01DA013240

    Keywords

    • Adolescent
    • Adult
    • Aged
    • Brain
    • Child
    • Child, Preschool
    • European Continental Ancestry Group
    • Female
    • Genome-Wide Association Study
    • Humans
    • Infant
    • Intelligence
    • Journal Article
    • Linkage Disequilibrium
    • Male
    • Meta-Analysis
    • Middle Aged
    • Nerve Tissue Proteins
    • Polymorphism, Single Nucleotide
    • Young Adult

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