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

TitleStudy of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Publication TypeJournal Article
Year of Publication2018
AuthorsDavies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, W Hill, D, 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, M Ikram, A, 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, B Windham, G, 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, EDrabant, 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, P Slagboom, E, 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, K Wen, H, 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, M Ikram, K, J Jukema, W, 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, 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
JournalNat Commun
Volume9
Issue1
Pagination2098
Date Published2018 May 29
ISSN2041-1723
KeywordsAdolescent, 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
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) 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.
DOI10.1038/s41467-018-04362-x
Alternate JournalNat Commun
PubMed ID29844566
PubMed Central IDPMC5974083
Grant ListMC_PC_17228 / MRC_ / Medical Research Council / United Kingdom
U01 AG009740 / AG / NIA NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 MH085018 / MH / NIMH NIH HHS / United States
MC_UU_12011/1 / MRC_ / Medical Research Council / United Kingdom
MR/R023484/1 / MRC_ / Medical Research Council / United Kingdom
G0600237 / MRC_ / Medical Research Council / United Kingdom
U01 HL096814 / HL / NHLBI NIH HHS / United States
R01 AG055406 / AG / NIA NIH HHS / United States
MC_U147585827 / MRC_ / Medical Research Council / United Kingdom
U54 GM115428 / GM / NIGMS NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 AG049789 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
BB/F022441/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
U01 HL096917 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
G0400491 / MRC_ / Medical Research Council / United Kingdom
MC_U147585819 / MRC_ / Medical Research Council / United Kingdom
U01 HL096902 / HL / NHLBI NIH HHS / United States
L30 MH104879 / MH / NIMH NIH HHS / United States
MC_UU_12011/2 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_UP_A620_1014 / MRC_ / Medical Research Council / United Kingdom
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
G0100594 / MRC_ / Medical Research Council / United Kingdom
U01 AG052409 / AG / NIA NIH HHS / United States
MR/S015132/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL070825 / HL / NHLBI NIH HHS / United States
G0901461 / MRC_ / Medical Research Council / United Kingdom
MC_UP_A620_1017 / MRC_ / Medical Research Council / United Kingdom
U01 HL096899 / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
MC_UU_12011/4 / MRC_ / Medical Research Council / United Kingdom
MC_U147585824 / MRC_ / Medical Research Council / United Kingdom
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
U01 AG049505 / AG / NIA NIH HHS / United States

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