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

Publication ,  Journal Article
Davies, G; Lam, M; Harris, SE; Trampush, JW; Luciano, M; Hill, WD; Hagenaars, SP; Ritchie, SJ; Marioni, RE; Fawns-Ritchie, C; Liewald, DCM ...
Published in: Nat Commun
May 29, 2018

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 29, 2018

Volume

9

Issue

1

Start / End Page

2098

Location

England

Related Subject Headings

  • Young Adult
  • Reaction Time
  • Polymorphism, Single Nucleotide
  • Neurodevelopmental Disorders
  • Neurodegenerative Diseases
  • Multifactorial Inheritance
  • Middle Aged
  • Mental Disorders
  • Humans
  • Genetic Predisposition to Disease
 

Citation

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Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2018). Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun, 9(1), 2098. https://doi.org/10.1038/s41467-018-04362-x
Davies, Gail, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W David Hill, Saskia P. Hagenaars, et al. “Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.Nat Commun 9, no. 1 (May 29, 2018): 2098. https://doi.org/10.1038/s41467-018-04362-x.
Davies G, Lam M, Harris SE, Trampush JW, Luciano M, Hill WD, et al. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun. 2018 May 29;9(1):2098.
Davies, Gail, et al. “Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.Nat Commun, vol. 9, no. 1, May 2018, p. 2098. Pubmed, doi:10.1038/s41467-018-04362-x.
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. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun. 2018 May 29;9(1):2098.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 29, 2018

Volume

9

Issue

1

Start / End Page

2098

Location

England

Related Subject Headings

  • Young Adult
  • Reaction Time
  • Polymorphism, Single Nucleotide
  • Neurodevelopmental Disorders
  • Neurodegenerative Diseases
  • Multifactorial Inheritance
  • Middle Aged
  • Mental Disorders
  • Humans
  • Genetic Predisposition to Disease