SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

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; Lill, CM; 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

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview
[img]
Preview
PDF (Supplementary information) Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
[img]
Preview
PDF (Description of additional supplementary files) Published Version
Available under License Creative Commons Attribution.

Download (192kB) | Preview
[img] Microsoft Excel (Supplementary data 1) Published Version
Available under License Creative Commons Attribution.

Download (3MB)
[img] Microsoft Excel (Supplementary data 2) Published Version
Available under License Creative Commons Attribution.

Download (2MB)
[img] Microsoft Excel (Supplementary data 3) Published Version
Available under License Creative Commons Attribution.

Download (4MB)
[img] Microsoft Excel (Supplementary data 4) Published Version
Available under License Creative Commons Attribution.

Download (2MB)
[img] Microsoft Excel (Supplementary data 5) Published Version
Available under License Creative Commons Attribution.

Download (168kB)
[img] Microsoft Excel (Supplementary data 6) Published Version
Available under License Creative Commons Attribution.

Download (392kB)
[img] Microsoft Excel (Supplementary data 7) Published Version
Available under License Creative Commons Attribution.

Download (633kB)
[img] Microsoft Excel (Supplementary data 8) Published Version
Available under License Creative Commons Attribution.

Download (13kB)
[img] Microsoft Excel (Supplementary data 9) Published Version
Available under License Creative Commons Attribution.

Download (14kB)
[img] Microsoft Excel (Supplementary data 10) Published Version
Available under License Creative Commons Attribution.

Download (239kB)
[img] Microsoft Excel (Supplementary data 11) Published Version
Available under License Creative Commons Attribution.

Download (723kB)
[img] Microsoft Excel (Supplementary data 12) Published Version
Available under License Creative Commons Attribution.

Download (647kB)
[img] Microsoft Excel (Supplementary data 13) Published Version
Available under License Creative Commons Attribution.

Download (20kB)
[img] Microsoft Excel (Supplementary data 14) Published Version
Available under License Creative Commons Attribution.

Download (646kB)
[img] Microsoft Excel (Supplementary data 15) Published Version
Available under License Creative Commons Attribution.

Download (12kB)
[img] Microsoft Excel (Supplementary data 16) Published Version
Available under License Creative Commons Attribution.

Download (27kB)
[img] Microsoft Excel (Supplementary data 17) Published Version
Available under License Creative Commons Attribution.

Download (16kB)
[img] Microsoft Excel (Supplementary data 18) Published Version
Available under License Creative Commons Attribution.

Download (16kB)
[img] Microsoft Excel (Supplementary data 19) Published Version
Available under License Creative Commons Attribution.

Download (20kB)
[img] Microsoft Excel (Supplementary data 20) Published Version
Available under License Creative Commons Attribution.

Download (14kB)

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: Correction available at https://doi.org/10.1038/s41467-019-10160-w 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: Adolescent, Adult, Aged, Aged, 80 and over, Cognition, Genetic Loci, Genetic Predisposition to Disease, Humans, Mental Disorders, Middle Aged, Multifactorial Inheritance, Neurodegenerative Diseases, Neurodevelopmental Disorders, Polymorphism, Single Nucleotide, Reaction Time, Young Adult, Humans, Neurodegenerative Diseases, Genetic Predisposition to Disease, Cognition, Reaction Time, Mental Disorders, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Young Adult, Genetic Loci, Neurodevelopmental Disorders, 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
MC_UU_00007/10Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_U147585827Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U01 AG009740NIA NIH HHSUNSPECIFIED
U01 HL096917NHLBI NIH HHSUNSPECIFIED
MC_UU_12011/2Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 MH085018NIMH NIH HHSUNSPECIFIED
MR/K026992/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/S015132/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U01 HL096814NHLBI NIH HHSUNSPECIFIED
R01 AG055406NIA NIH HHSUNSPECIFIED
U01 AG052409NIA NIH HHSUNSPECIFIED
MC_UU_12011/4Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U01 AG049505NIA NIH HHSUNSPECIFIED
U01 HL096812NHLBI NIH HHSUNSPECIFIED
R01 NS017950NINDS NIH HHSUNSPECIFIED
R01 AG054076NIA NIH HHSUNSPECIFIED
R01 AG049789NIA NIH HHSUNSPECIFIED
RF1 AG015819NIA NIH HHSUNSPECIFIED
MC_QA137853Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U01 HL130114NHLBI NIH HHSUNSPECIFIED
U01 HL096902NHLBI NIH HHSUNSPECIFIED
MC_U147585819Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 HL105756NHLBI NIH HHSUNSPECIFIED
MC_UP_A620_1014Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
P30 AG010161NIA NIH HHSUNSPECIFIED
R01 AG033193NIA NIH HHSUNSPECIFIED
MC_UP_A620_1017Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12011/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 HL070825NHLBI NIH HHSUNSPECIFIED
U01 HL096899NHLBI NIH HHSUNSPECIFIED
P30 AG010129NIA NIH HHSUNSPECIFIED
MC_PC_17228Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/F019394/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UL1 TR001881NCATS NIH HHSUNSPECIFIED
G0400491Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0600237Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0100594Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U54 GM115428NIGMS NIH HHSUNSPECIFIED
MC_U147585824Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/F022441/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
G0901461Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
HHSN268201700004INHLBI NIH HHSUNSPECIFIED
PubMed ID: 29844566
Web of Science ID: WOS:000433297900009
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110464
Publisher's version: https://doi.org/10.1038/s41467-018-04362-x

Actions (login required)

Edit Item Edit Item