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

Davies, Gail; Lam, Max; Liewald, David C. M.; Knopman, DS; Kochan, NA; Konte, B; Kwok, JB; Le Hellard, S; Lee, T; Lehtimaki, T; Li, S-C; Liu, T; Koini, M; Okely, Judith A.; London, E; Longstreth, WT; Lopez, OL; Loukola, A; Luck, T; Lundervold, AJ; Lundquist, A; Lyytikainen, L-P; Martin, NG; Montgomery, GW; Ahola-Olli, Ari V.; Murray, AD; Need, AC; Noordam, R; Nyberg, L; Ollier, W; Papenberg, G; Pattie, A; Polasek, O; Poldrack, RA; Psaty, BM; Barnes, Catriona L. K.; Reppermund, S; Riedel-Heller, SG; Rose, RJ; Rotter, JI; Roussos, P; Rovio, SP; Saba, Y.; Sabb, FW; Sachdev, PS; Satizabal, CL; Bertram, Lars; Schmid, M; Scott, Rodney J.; Scult, MA; Simino, J; Slagboom, PE; Smyrnis, N; Soumare, A; Stefanis, NC; Stott, DJ; Straub, RE; Bis, Joshua C.; Sundet, K; Taylor, AM; Taylor, KD; Tzoulaki, I; Tzourio, C; Uitterlinden, A; Vitart, V; Voineskos, AN; Kaprio, J; Wagner, M; Burdick, Katherine E.; Wagner, H; Weinhold, L; Wen, KH; Widen, E; Yang, Q; Zhao, W; Adams, HHH; Arking, DE; Bilder, RM; Bitsios, P; Christoforou, Andrea; Boerwinkle, E; Chiba-Falek, O; Corvin, A; De Jager, PL; Debette, S; Donohoe, G; Elliott, P; Fitzpatrick, AL; Gill, M; Glahn, DC; DeRosse, Pamela; Hagg, S; Hansell, NK; Hariri, AR; Ikram, MK; Jukema, JW; Vuoksimaa, E; Keller, MC; Kremen, WS; Launer, L; Lindenberger, U; Djurovic, Srdjan; Palotie, A; Pedersen, NL; Pendleton, N; Porteous, DJ; Raikkonen, K; Raitakari, OT; Ramirez, A; Reinvang, I; Rudan, I; Rujescu, D; Harris, Sarah E.; Espeseth, Thomas; Schmidt, R; Schmidt, H; Schofield, PW; Schofield, PR; Starr, JM; Steen, VM; Trollor, JN; Turner, ST; Van Duijn, CM; Villringer, A; Giakoumaki, Stella; Weinberger, DR; Weir, DR; Wilson, JF; Malhotra, A; McIntosh, AM; Gale, CR; Seshadri, S; Mosley, TH; Bressler, J; Lencz, T; Giddaluru, S; Deary, IJ; Gustavson, DE; Hayward, C; Hofer, E; Ikram, MA; Karlsson, R; Knowles, E; Lahti, J; Trampush, Joey W.; Leber, M; Li, S; Mather, KA; Melle, I; Morris, D; Oldmeadow, Christopher; Palviainen, T; Payton, A; Pazoki, R; Petrovic, K; Luciano, Michelle; Reynolds, CA; Sargurupremraj, M; Scholz, M; Smith, JA; Smith, AV; Terzikhan, N; Thalamuthu, A; Trompet, S; van der Lee, SJ; Ware, EB; Hill, W. David; Windham, BG; Wright, MJ; Yang, J; Yu, J; Ames, D; Amin, N; Amouyel, P; Andreassen, OA; Armstrong, NJ; Assareh, AA; Hagenaars, Saskia P.; Attia, John R.; Attix, D; Avramopoulos, D; Bennett, DA; Boehmer, AC; Boyle, PA; Brodaty, H; Campbell, H; Cannon, TD; Cirulli, ET; Ritchie, Stuart J.; Congdon, E; Conley, ED; Corley, J; Cox, SR; Dale, AM; Dehghan, A; Dick, D; Dickinson, D; Eriksson, JG; Evangelou, E; Marioni, Riccardo E.; Faul, JD; Ford, I; Freimer, NA; Gao, H; Giegling, I; Gillespie, NA; Gordon, SD; Gottesman, RF; Griswold, ME; Gudnason, V; Fawns-Ritchie, Chloe; Harris, TB; Hartmann, AM; Hatzimanolis, A; Heiss, G; Holliday, Elizabeth G.; Joshi, PK; Kahonen, M; Kardia, SLR; Karlsson, I; Kleineidam, L

Title: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Creator: Davies, Gail; Lam, Max; Liewald, David C. M.; Knopman, DS; Kochan, NA; Konte, B; Kwok, JB; Le Hellard, S; Lee, T; Lehtimaki, T; Li, S-C; Liu, T; Koini, M; Okely, Judith A.; London, E; Longstreth, WT; Lopez, OL; Loukola, A; Luck, T; Lundervold, AJ; Lundquist, A; Lyytikainen, L-P; Martin, NG; Montgomery, GW; Ahola-Olli, Ari V.; Murray, AD; Need, AC; Noordam, R; Nyberg, L; Ollier, W; Papenberg, G; Pattie, A; Polasek, O; Poldrack, RA; Psaty, BM; Barnes, Catriona L. K.; Reppermund, S; Riedel-Heller, SG; Rose, RJ; Rotter, JI; Roussos, P; Rovio, SP; Saba, Y.; Sabb, FW; Sachdev, PS; Satizabal, CL; Bertram, Lars; Schmid, M; Scott, Rodney J.; Scult, MA; Simino, J; Slagboom, PE; Smyrnis, N; Soumare, A; Stefanis, NC; Stott, DJ; Straub, RE; Bis, Joshua C.; Sundet, K; Taylor, AM; Taylor, KD; Tzoulaki, I; Tzourio, C; Uitterlinden, A; Vitart, V; Voineskos, AN; Kaprio, J; Wagner, M; Burdick, Katherine E.; Wagner, H; Weinhold, L; Wen, KH; Widen, E; Yang, Q; Zhao, W; Adams, HHH; Arking, DE; Bilder, RM; Bitsios, P; Christoforou, Andrea; Boerwinkle, E; Chiba-Falek, O; Corvin, A; De Jager, PL; Debette, S; Donohoe, G; Elliott, P; Fitzpatrick, AL; Gill, M; Glahn, DC; DeRosse, Pamela; Hagg, S; Hansell, NK; Hariri, AR; Ikram, MK; Jukema, JW; Vuoksimaa, E; Keller, MC; Kremen, WS; Launer, L; Lindenberger, U; Djurovic, Srdjan; Palotie, A; Pedersen, NL; Pendleton, N; Porteous, DJ; Raikkonen, K; Raitakari, OT; Ramirez, A; Reinvang, I; Rudan, I; Rujescu, D; Harris, Sarah E.; Espeseth, Thomas; Schmidt, R; Schmidt, H; Schofield, PW; Schofield, PR; Starr, JM; Steen, VM; Trollor, JN; Turner, ST; Van Duijn, CM; Villringer, A; Giakoumaki, Stella; Weinberger, DR; Weir, DR; Wilson, JF; Malhotra, A; McIntosh, AM; Gale, CR; Seshadri, S; Mosley, TH; Bressler, J; Lencz, T; Giddaluru, S; Deary, IJ; Gustavson, DE; Hayward, C; Hofer, E; Ikram, MA; Karlsson, R; Knowles, E; Lahti, J; Trampush, Joey W.; Leber, M; Li, S; Mather, KA; Melle, I; Morris, D; Oldmeadow, Christopher; Palviainen, T; Payton, A; Pazoki, R; Petrovic, K; Luciano, Michelle; Reynolds, CA; Sargurupremraj, M; Scholz, M; Smith, JA; Smith, AV; Terzikhan, N; Thalamuthu, A; Trompet, S; van der Lee, SJ; Ware, EB; Hill, W. David; Windham, BG; Wright, MJ; Yang, J; Yu, J; Ames, D; Amin, N; Amouyel, P; Andreassen, OA; Armstrong, NJ; Assareh, AA; Hagenaars, Saskia P.; Attia, John R.; Attix, D; Avramopoulos, D; Bennett, DA; Boehmer, AC; Boyle, PA; Brodaty, H; Campbell, H; Cannon, TD; Cirulli, ET; Ritchie, Stuart J.; Congdon, E; Conley, ED; Corley, J; Cox, SR; Dale, AM; Dehghan, A; Dick, D; Dickinson, D; Eriksson, JG; Evangelou, E; Marioni, Riccardo E.; Faul, JD; Ford, I; Freimer, NA; Gao, H; Giegling, I; Gillespie, NA; Gordon, SD; Gottesman, RF; Griswold, ME; Gudnason, V; Fawns-Ritchie, Chloe; Harris, TB; Hartmann, AM; Hatzimanolis, A; Heiss, G; Holliday, Elizabeth G.; Joshi, PK; Kahonen, M; Kardia, SLR; Karlsson, I; Kleineidam, L
Relation: Nature Communications Vol. 9, Issue 1, no. 2098
Publisher Link: http://dx.doi.org/10.1038/s41467-018-04362-x
Publisher: Nature Publishing Group
Resource Type: journal article
Date: 2018
Description: 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.
Subject: adolescent; adult; aged; cognition; genetic loci; mental disorders
Identifier: http://hdl.handle.net/1959.13/1441293
Identifier: uon:41379
Identifier: ISSN:2041-1723
Rights: 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/.
Language: eng
Full Text
Reviewed

Hits: 103708
Visitors: 103329
Downloads: 204

		Thumbnail	File	Description	Size	Format
View Details Download			ATTACHMENT02	Publisher version (open access)	3 MB	Adobe Acrobat PDF	View Details Download