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

Savage, J. E.; Jansen, P. R.; Stringer, S.; Watanabe, K.; Bryois, J.; De Leeuw, C. A.; Nagel, M.; Awasthi, S.; Barr, P. B.; Coleman, J. R. I.; Grasby, K. L.; Hammerschlag, A. R.; Kaminski, J. A.; Karlsson, R.; Krapohl, E.; Lam, M.; Nygaard, M.; Reynolds, C. A.; Trampush, J. W.; Young, H.; Zabaneh, D.; Hägg, S.; Hansell, N. K.; Karlsson, Ida K.; Linnarsson, S.; Montgomery, G. W.; Muñoz-Manchado, A. B.; Quinlan, E. B.; Schumann, G.; Skene, N. G.; Webb, B. T.; White, T.; Arking, D. E.; Avramopoulos, D.; Bilder, R. M.; Bitsios, P.; Burdick, K. E.; Cannon, T. D.; Chiba-Falek, O.; Christoforou, A.; Cirulli, E. T.; Congdon, E.; Corvin, A.; Davies, G.; Deary, I. J.; Derosse, P.; Dickinson, D.; Djurovic, S.; Donohoe, G.; Conley, E. D.; Eriksson, J. G.; Espeseth, T.; Freimer, N. A.; Giakoumaki, S.; Giegling, I.; Gill, M.; Glahn, D. C.; Hariri, A. R.; Hatzimanolis, A.; Keller, M. C.; Knowles, E.; Koltai, D.; Konte, B.; Lahti, J.; Le Hellard, S.; Lencz, T.; Liewald, D. C.; London, E.; Lundervold, A. J.; Malhotra, A. K.; Melle, I.; Morris, D.; Need, A. C.; Ollier, W.; Palotie, A.; Payton, A.; Pendleton, N.; Poldrack, R. A.; Räikkönen, K.; Reinvang, I.; Roussos, P.; Rujescu, D.; Sabb, F. W.; Scult, M. A.; Smeland, O. B.; Smyrnis, N.; Starr, J. M.; Steen, V. M.; Stefanis, N. C.; Straub, R. E.; Sundet, K.; Tiemeier, H.; Voineskos, A. N.; Weinberger, D. R.; Widen, E.; Yu, J.; Abecasis, G.; Andreassen, O. A.; Breen, G.; Christiansen, L.; Debrabant, B.; Dick, D. M.; Heinz, A.; Hjerling-Leffler, J.; Ikram, M. A.; Kendler, K. S.; Martin, N. G.; Medland, S. E.; Pedersen, N. L.; Plomin, R.; Polderman, T. J. C.; Ripke, S.; Van Der Sluis, S.; Sullivan, P. F.; Vrieze, S. I.; Wright, M. J.; Posthuma, D.

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

Savage, J. E.

Jansen, P. R.

Stringer, S.

Watanabe, K.

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2018 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 7, p. 912-919Article in journal (Refereed) Published

Abstract [en]

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, 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.

Place, publisher, year, edition, pages

Nature Publishing Group, 2018. Vol. 50, no 7, p. 912-919

Keywords [en]

Alzheimer disease, Article, attention deficit disorder, chromatin, conserved sequence, corpus striatum, exon, expression quantitative trait locus, gene expression, gene location, gene locus, gene mapping, genetic association, genetic correlation, genetic variability, genome-wide association study, heredity, hippocampus, human, intelligence, medium spiny neuron, Mendelian randomization analysis, nervous system development, pleiotropy, priority journal, pyramidal nerve cell, schizophrenia, synapse

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Neurology

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URN: urn:nbn:se:hj:diva-41590DOI: 10.1038/s41588-018-0152-6ISI: 000437224400005PubMedID: 29942086Scopus ID: 2-s2.0-85048943479OAI: oai:DiVA.org:hj-41590DiVA, id: diva2:1251139

Available from: 2018-09-26 Created: 2018-09-26 Last updated: 2018-09-26Bibliographically approved

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Karlsson, Ida K.

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