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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, Ikram, AM, 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, 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
Abstract<p>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.</p>
DOI10.1038/s41467-018-04362-x
Alternate JournalNat Commun
PubMed ID29844566
PubMed Central IDPMC5974083
Grant ListMC_UU_12011/2 / / Medical Research Council / United Kingdom
R01 MH085018 / MH / NIMH NIH HHS / United States
MC_U147585819 / / Medical Research Council / United Kingdom
R01 AG033193 / AG / NIA NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
ePub date: 
18/05