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

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Savage, J. E. (author)

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

Article/chapterEnglish2018

Publisher, publication year, extent ...

2018-06-25
Nature Publishing Group,2018
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LIBRIS-ID:oai:DiVA.org:hj-41590
https://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-41590URI
https://doi.org/10.1038/s41588-018-0152-6DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:138685382URI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
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

Added entries (persons, corporate bodies, meetings, titles ...)

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

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In:Nature Genetics: Nature Publishing Group50:7, s. 912-9191061-40361546-1718

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By the author/editor: Savage, J. E.; Jansen, P. R.; Stringer, S.; Watanabe, K.; Bryois, J.; De Leeuw, C. A.; show more...; Nagel, M.; Awasthi, S.; Barr, P. B.; Coleman, J. R. I ...; Grasby, K. L.; Hammerschlag, A. ...; 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, ...; 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 ...; Ikram, M. A.; Kendler, K. S.; Martin, N. G.; Medland, S. E.; Pedersen, N. L.; Plomin, R.; Polderman, T. J. ...; Ripke, S.; Van Der Sluis, S ...; Sullivan, P. F.; Vrieze, S. I.; Wright, M. J.; Posthuma, D.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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