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

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3085500 55 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2018 The Author(s).
Έτος δημοσίευσης:
2018
Συγγραφείς:
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, I.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.
Περιοδικό:
Nature Genetics
Εκδότης:
Nature Publishing Group
Τόμος:
50
Αριθμός / τεύχος:
7
Σελίδες:
912-919
Λέξεις-κλειδιά:
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; adolescent; brain; female; genetic predisposition; genetics; intelligence; male; meta analysis; middle aged; physiology; procedures; quantitative trait locus; single nucleotide polymorphism, Adolescent; Brain; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Intelligence; Male; Middle Aged; Polymorphism, Single Nucleotide; Quantitative Trait Loci
Επίσημο URL (Εκδότης):
DOI:
10.1038/s41588-018-0152-6
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