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

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Title: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Authors: 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
Boehmer, 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
Kahonen, M
Kardia, SLR
Karlsson, I
Kleineidam, L
Knopman, DS
Kochan, NA
Konte, B
Kwok, JB
Le Hellard, S
Lee, T
Lehtimaki, T
Li, S-C
Liu, T
Koini, M
London, E
Longstreth, WT
Lopez, OL
Loukola, A
Luck, T
Lundervold, AJ
Lundquist, A
Lyytikainen, 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
Soumare, 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
Hagg, 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
Raikkonen, K
Raitakari, OT
Ramirez, A
Reinvang, I
Rudan, I
Rujescu, D
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
Item Type: Journal Article
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.
Issue Date: 29-May-2018
Date of Acceptance: 23-Apr-2018
URI: http://hdl.handle.net/10044/1/60547
DOI: https://dx.doi.org/10.1038/s41467-018-04362-x
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 9
Issue: 1
Copyright Statement: © The Author(s) 2018. 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/.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GENOME-WIDE ASSOCIATION
HUMAN INTELLIGENCE
REACTION-TIME
EDUCATIONAL-ATTAINMENT
PARKINSONS-DISEASE
PROCESSING SPEED
COMMON VARIANTS
HUMAN LONGEVITY
OLD-AGE
METAANALYSIS
MD Multidisciplinary
Publication Status: Published
Article Number: 2098
Appears in Collections:Department of Medicine
Epidemiology, Public Health and Primary Care



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