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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.
Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan RI; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene
In: Nature genetics, vol 50, iss 7 (2018)
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, 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.
Keyword: Adolescent; Biological Sciences; Brain; Developmental Biology; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Intelligence; Male; Medical and Health Sciences; Middle Aged; Polymorphism; Quantitative Trait Loci; Single Nucleotide
URL: https://escholarship.org/uc/item/869275xx
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Novel genetic loci associated with hippocampal volume
In: ISSN: 2041-1723 ; EISSN: 2041-1723 ; Nature Communications ; https://hal.archives-ouvertes.fr/hal-01488337 ; Nature Communications, Nature Publishing Group, 2017, 8, pp.13624. ⟨10.1038/ncomms13624⟩ (2017)
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Novel genetic loci underlying human intracranial volume identified through genome-wide association
In: ISSN: 1097-6256 ; EISSN: 1546-1726 ; Nature Neuroscience ; https://hal.archives-ouvertes.fr/hal-01382716 ; Nature Neuroscience, Nature Publishing Group, 2016, 19 (12), pp.1569-1582. ⟨10.1038/nn.4398⟩ (2016)
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5
Common genetic variants influence human subcortical brain structures.
In: ISSN: 0028-0836 ; EISSN: 1476-4679 ; Nature ; https://hal.archives-ouvertes.fr/hal-01196805 ; Nature, Nature Publishing Group, 2015, 520 (7546), pp.224-9. ⟨10.1038/nature14101⟩ (2015)
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6
Genetic Basis of a Cognitive Complexity Metric
Hansell, Narelle K.; Halford, Graeme S.; Andrews, Glenda. - : Public Library of Science, 2015
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7
Genetic basis of a cognitive complexity metric
Hansell, Narelle K.; Halford, Graeme S.; Andrews, Glenda. - : Public Library of Science, 2015
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8
The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
In: ISSN: 1931-7557 ; EISSN: 1931-7565 ; Brain imaging and behavior (Brain Imaging Behav) ; https://hal-pasteur.archives-ouvertes.fr/pasteur-01967166 ; Brain imaging and behavior (Brain Imaging Behav), Secaucus, NJ : Springer, 2014, 8 (2), pp.152-182. ⟨10.1007/s11682-013-9269-5⟩ (2014)
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Genome-wide association studies establish that human intelligence is highly heritable and polygenic
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