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

Sniekers, Suzanne and Stringer, Sven and Watanabe, Kyoko and Jansen, Philip R and Coleman, Jonathan RI and Krapohl, Eva and Taskesen, Erdogan and Hammerschlag, Anke R and Okbay, Aysu and Zabaneh, Delilah and Amin, Najaf and Breen, Gerome and Cesarini, David and Chabris, Christopher F and Iacono, William G and Ikram, M Arfan and Johannesson, Magnus and Koellinger, Philipp and Lee, James J and Magnusson, Patrik KE and McGue, Matt and Miller, Mike B and Ollier, William ER and Payton, Antony and Pendleton, Neil and Plomin, Robert and Rietveld, Cornelius A and Tiemeier, Henning and van Duijn, Cornelia M and Posthuma, Danielle (2017) Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nature Genetics, 49 (7). pp. 1107-1112. ISSN 1061-4036

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Abstract

Intelligence is associated with important economic and health-related life outcomes1. Despite intelligence having substantial heritability2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered3,4,5. 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 heritability2 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.

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