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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Davies, G; Lam, M; Harris, SE; Trampush, JW; Luciano, M; Hill, WD; Hagenaars, SP; Ritchie, SJ; Marioni, RE; Fawns-Ritchie, C; et al. Davies, G; Lam, M; Harris, SE; Trampush, JW; Luciano, M; Hill, WD; Hagenaars, SP; Ritchie, SJ; Marioni, RE; Fawns-Ritchie, C; Liewald, DCM; Okely, JA; Ahola-Olli, AV; Barnes, CLK; Bertram, L; Bis, JC; Burdick, KE; Christoforou, A; DeRosse, P; Djurovic, S; Espeseth, T; Giakoumaki, S; Giddaluru, S; Gustavson, DE; Hayward, C; Hofer, E; Ikram, MA; Karlsson, R; Knowles, E; Lahti, J; Leber, M; Li, S; Mather, KA; Melle, I; Morris, D; Oldmeadow, C; Palviainen, T; Payton, A; Pazoki, R; Petrovic, K; Reynolds, CA; Sargurupremraj, M; Scholz, M; Smith, JA; Smith, AV; Terzikhan, N; Thalamuthu, A; Trompet, S; van der Lee, SJ; Ware, EB; Windham, BG; Wright, MJ; Yang, J; Yu, J; Ames, D; Amin, N; Amouyel, P; Andreassen, OA; Armstrong, NJ; Assareh, AA; Attia, JR; Attix, D; Avramopoulos, D; Bennett, DA; Böhmer, AC; Boyle, PA; Brodaty, H; Campbell, H; Cannon, TD; Cirulli, ET; Congdon, E; Conley, ED; Corley, J; Cox, SR; Dale, AM; Dehghan, A; Dick, D; Dickinson, D; Eriksson, JG; Evangelou, E; Faul, JD; Ford, I; Freimer, NA; Gao, H; Giegling, I; Gillespie, NA; Gordon, SD; Gottesman, RF; Griswold, ME; Gudnason, V; Harris, TB; Hartmann, AM; Hatzimanolis, A; Heiss, G; Holliday, EG; Joshi, PK; Kähönen, M; Kardia, SLR; Karlsson, I; Kleineidam, L; Knopman, DS; Kochan, NA; Konte, B; Kwok, JB; Le Hellard, S; Lee, T; Lehtimäki, T; Li, S-C; Liu, T; Koini, M; London, E; Longstreth, WT; Lopez, OL; Loukola, A; Luck, T; Lundervold, AJ; Lundquist, A; Lyytikäinen, L-P; Martin, NG; Montgomery, GW; Murray, AD; Need, AC; Noordam, R; Nyberg, L; Ollier, W; Papenberg, G; Pattie, A; Polasek, O; Poldrack, RA; Psaty, BM; Reppermund, S; Riedel-Heller, SG; Rose, RJ; Rotter, JI; Roussos, P; Rovio, SP; Saba, Y; Sabb, FW; Sachdev, PS; Satizabal, CL; Schmid, M; Scott, RJ; Scult, MA; Simino, J; Slagboom, PE; Smyrnis, N; Soumaré, A; Stefanis, NC; Stott, DJ; Straub, RE; Sundet, K; Taylor, AM; Taylor, KD; Tzoulaki, I; Tzourio, C; Uitterlinden, A; Vitart, V; Voineskos, AN; Kaprio, J; Wagner, M; Wagner, H; Weinhold, L; Wen, KH; Widen, E; Yang, Q; Zhao, W; Adams, HHH; Arking, DE; Bilder, RM; Bitsios, P; Boerwinkle, E; Chiba-Falek, O; Corvin, A; De Jager, PL; Debette, S; Donohoe, G; Elliott, P; Fitzpatrick, AL; Gill, M; Glahn, DC; Hägg, S; Hansell, NK; Hariri, AR; Ikram, MK; Jukema, JW; Vuoksimaa, E; Keller, MC; Kremen, WS; Launer, L; Lindenberger, U; Palotie, A; Pedersen, NL; Pendleton, N; Porteous, DJ; Räikkönen, K; Raitakari, OT; Ramirez, A; Reinvang, I; Rudan, I; Dan Rujescu; Schmidt, R; Schmidt, H; Schofield, PW; Schofield, PR; Starr, JM; Steen, VM; Trollor, JN; Turner, ST; Van Duijn, CM; Villringer, A; Weinberger, DR; Weir, DR; Wilson, JF; Malhotra, A; McIntosh, AM; Gale, CR; Seshadri, S; Mosley, TH; Bressler, J; Lencz, T; Deary, IJ (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun, 9 (1). p. 2098. ISSN 2041-1723 https://doi.org/10.1038/s41467-018-04362-x
SGUL Authors: Malhotra, Aneil

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Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2018
Keywords: MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Nat Commun
ISSN: 2041-1723
Language: eng
Dates:
DateEvent
29 May 2018Published
23 April 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
RF1 AG015819NIA NIH HHSUNSPECIFIED
U01 AG009740NIA NIH HHSUNSPECIFIED
MC_UU_12011/2Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 MH085018NIMH NIH HHSUNSPECIFIED
MC_U147585819Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 AG033193NIA NIH HHSUNSPECIFIED
HHSN268201700004INHLBI NIH HHSUNSPECIFIED
U01 AG052409NIA NIH HHSUNSPECIFIED
R01 HL070825NHLBI NIH HHSUNSPECIFIED
UL1 TR001881NCATS NIH HHSUNSPECIFIED
U01 AG049505NIA NIH HHSUNSPECIFIED
MR/K026992/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 29844566
Web of Science ID: WOS:000433297900009
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/110464
Publisher's version: https://doi.org/10.1038/s41467-018-04362-x

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