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

G. Davies; M. Lam; S.E. Harris; J.W. Trampush; M. Luciano; W.D. Hill; S.P. Hagenaars; S.J. Ritchie; R.E. Marioni; C. Fawns-Ritchie; D.C.M. Liewald; J.A. Okely; A.V. Ahola-Olli; C.L.K. Barnes; L. Bertram; J.C. Bis; K.E. Burdick; A. Christoforou; P. DeRosse; S. Djurovic; T. Espeseth; S. Giakoumaki; S. Giddaluru; D.E. Gustavson; C. Hayward; E. Hofer; M.A. Ikram; R. Karlsson; E. Knowles; J. Lahti; M. Leber; S. Li; K.A. Mather; I. Melle; D. Morris; C. Oldmeadow; T. Palviainen; A. Payton; R. Pazoki; K. Petrovic; C.A. Reynolds; M. Sargurupremraj; M. Scholz; J.A. Smith; A.V. Smith; N. Terzikhan; A. Thalamuthu; S. Trompet; S.J. van der Lee; E.B. Ware; B.G. Windham; M.J. Wright; J. Yang; J. Yu; D. Ames; N. Amin; P. Amouyel; O.A. Andreassen; N.J. Armstrong; A.A. Assareh; J.R. Attia; D. Attix; D. Avramopoulos; D.A. Bennett; A.C. Böhmer; P.A. Boyle; H. Brodaty; H. Campbell; T.D. Cannon; E.T. Cirulli; E. Congdon; E.D. Conley; J. Corley; S.R. Cox; A.M. Dale; A. Dehghan; D. Dick; D. Dickinson; J.G. Eriksson; E. Evangelou; J.D. Faul; I. Ford; N.A. Freimer; H. Gao; I. Giegling; N.A. Gillespie; S.D. Gordon; R.F. Gottesman; M.E. Griswold; V. Gudnason; T.B. Harris; A.M. Hartmann; A. Hatzimanolis; G. Heiss; E.G. Holliday; P.K. Joshi; M. Kähönen; S.L.R. Kardia; I. Karlsson; L. Kleineidam; D.S. Knopman; N.A. Kochan; B. Konte; J.B. Kwok; S. Le Hellard; T. Lee; T. Lehtimäki; S-C Li; T. Liu; M. Koini; E. London; W.T. Longstreth; O.L. Lopez; A. Loukola; T. Luck; A.J. Lundervold; A. Lundquist; L-P Lyytikäinen; N.G. Martin; G.W. Montgomery; A.D. Murray; A.C. Need; R. Noordam; L. Nyberg; W. Ollier; G. Papenberg; A. Pattie; O. Polasek; R.A. Poldrack; B.M. Psaty; S. Reppermund; S.G. Riedel-Heller; R.J. Rose; J.I. Rotter; P. Roussos; S.P. Rovio; Y. Saba; F.W. Sabb; P.S. Sachdev; C.L. Satizabal; M. Schmid; R.J. Scott; M.A. Scult; J. Simino; P.E. Slagboom; N. Smyrnis; A. Soumaré; N.C. Stefanis; D.J. Stott; R.E. Straub; K. Sundet; A.M. Taylor; K.D. Taylor; I. Tzoulaki; C. Tzourio; A. Uitterlinden; V. Vitart; A.N. Voineskos; J. Kaprio; M. Wagner; H. Wagner; L. Weinhold; K.H. Wen; E. Widen; Q. Yang; W. Zhao; H.H.H. Adams; D.E. Arking; R.M. Bilder; P. Bitsios; E. Boerwinkle; O. Chiba-Falek; A. Corvin; P.L. De Jager; S. Debette; G. Donohoe; P. Elliott; A.L. Fitzpatrick; M. Gill; D.C. Glahn; S. Hägg; N.K. Hansell; A.R. Hariri; M.K. Ikram; J.W. Jukema; E. Vuoksimaa; M.C. Keller; W.S. Kremen; L. Launer; U. Lindenberger; A. Palotie; N.L. Pedersen; N. Pendleton; D.J. Porteous; K. Räikkönen; O.T. Raitakari; A. Ramirez; I. Reinvang; I. Rudan; D. Rujescu; R. Schmidt; H. Schmidt; P.W. Schofield; P.R. Schofield; J.M. Starr; V.M. Steen; J.N. Trollor; S.T. Turner; C.M. van Duijn; Arno Villringer; D.R. Weinberger; D.R. Weir; J.F. Wilson; A. Malhotra; A.M. McIntosh; C.R. Gale; S. Seshadri; T.H. Mosley; J. Bressler; T. Lencz; I.J. Deary

doi:10.1038/s41467-018-04362-x

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

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

G. Davies, M. Lam, S.E. Harris, J.W. Trampush, M. Luciano, W.D. Hill, S.P. Hagenaars, S.J. Ritchie, R.E. Marioni, C. Fawns-Ritchie, …

Nature Communications, Vol.9(1)

2018

DOI: https://doi.org/10.1038/s41467-018-04362-x

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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.

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Title: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Authors/Creators: G. Davies (Author/Creator) - University of Edinburgh
M. Lam (Author/Creator)
S.E. Harris (Author/Creator) - University of Edinburgh
J.W. Trampush (Author/Creator) - University of Southern California
M. Luciano (Author/Creator) - University of Edinburgh
W.D. Hill (Author/Creator) - University of Edinburgh
S.P. Hagenaars (Author/Creator) - University of Edinburgh
S.J. Ritchie (Author/Creator) - University of Edinburgh
R.E. Marioni (Author/Creator) - University of Edinburgh
C. Fawns-Ritchie (Author/Creator) - University of Edinburgh
D.C.M. Liewald (Author/Creator) - University of Edinburgh
J.A. Okely (Author/Creator) - University of Edinburgh
A.V. Ahola-Olli (Author/Creator) - University of Turku
C.L.K. Barnes (Author/Creator) - University of Edinburgh
L. Bertram (Author/Creator) - Max Planck Society
J.C. Bis (Author/Creator) - University of Washington
K.E. Burdick (Author/Creator) - Icahn School of Medicine at Mount Sinai
A. Christoforou (Author/Creator)
P. DeRosse (Author/Creator) - Northwell Health
S. Djurovic (Author/Creator) - University of Bergen
T. Espeseth (Author/Creator) - University of Oslo
S. Giakoumaki (Author/Creator) - University of Crete
S. Giddaluru (Author/Creator) - University of Bergen
D.E. Gustavson (Author/Creator) - University of California San Diego
C. Hayward (Author/Creator) - University of Edinburgh
E. Hofer (Author/Creator) - Medical University of Graz
M.A. Ikram (Author/Creator) - Erasmus University Rotterdam
R. Karlsson (Author/Creator) - Karolinska Institutet
E. Knowles (Author/Creator) - Yale University
J. Lahti (Author/Creator) - University of Helsinki
M. Leber (Author/Creator) - University of Cologne
S. Li (Author/Creator) - Boston University
K.A. Mather (Author/Creator) - UNSW Sydney
I. Melle (Author/Creator) - University of Bergen
D. Morris (Author/Creator) - Ollscoil na Gaillimhe – University of Galway
C. Oldmeadow (Author/Creator) - University of Newcastle Australia
T. Palviainen (Author/Creator) - University of Helsinki
A. Payton (Author/Creator) - University of Manchester
R. Pazoki (Author/Creator) - Imperial College London
K. Petrovic (Author/Creator) - Medical University of Graz
C.A. Reynolds (Author/Creator) - University of California, Riverside
M. Sargurupremraj (Author/Creator) - Université de Bordeaux
M. Scholz (Author/Creator) - Leipzig University
J.A. Smith (Author/Creator) - University of Michigan
A.V. Smith (Author/Creator) - University of Iceland
N. Terzikhan (Author/Creator) - Ghent University
A. Thalamuthu (Author/Creator) - UNSW Sydney
S. Trompet (Author/Creator) - Leiden University
S.J. van der Lee (Author/Creator) - Erasmus University Rotterdam
E.B. Ware (Author/Creator) - University of Michigan
B.G. Windham (Author/Creator) - University of Mississippi
M.J. Wright (Author/Creator) - The University of Queensland
J. Yang (Author/Creator) - Rush University Medical Center
J. Yu (Author/Creator) - Northwell Health
D. Ames (Author/Creator) - The University of Melbourne
N. Amin (Author/Creator) - Erasmus University Rotterdam
P. Amouyel (Author/Creator) - Lille University of Science and Technology
O.A. Andreassen (Author/Creator) - University of Oslo
N.J. Armstrong (Author/Creator) - Murdoch University
A.A. Assareh (Author/Creator) - UNSW Sydney
J.R. Attia (Author/Creator)
D. Attix (Author/Creator) - Duke University
D. Avramopoulos (Author/Creator) - Johns Hopkins University
D.A. Bennett (Author/Creator) - Rush University Medical Center
A.C. Böhmer (Author/Creator) - University of Bonn
P.A. Boyle (Author/Creator) - Rush University Medical Center
H. Brodaty (Author/Creator) - UNSW Sydney
H. Campbell (Author/Creator) - University of Edinburgh
T.D. Cannon (Author/Creator) - Yale University
E.T. Cirulli (Author/Creator)
E. Congdon (Author/Creator) - University of California, Los Angeles
E.D. Conley (Author/Creator)
J. Corley (Author/Creator) - University of Edinburgh
S.R. Cox (Author/Creator) - University of Edinburgh
A.M. Dale (Author/Creator) - University of California San Diego
A. Dehghan (Author/Creator) - Imperial College London
D. Dick (Author/Creator) - Virginia Commonwealth University
D. Dickinson (Author/Creator) - National Institutes of Health
J.G. Eriksson (Author/Creator) - Finnish Institute for Health and Welfare
E. Evangelou (Author/Creator) - Finnish Institute for Health and Welfare
J.D. Faul (Author/Creator) - University of Michigan
I. Ford (Author/Creator) - University of Glasgow
N.A. Freimer (Author/Creator)
H. Gao (Author/Creator) - Imperial College London
I. Giegling (Author/Creator) - Martin Luther University Halle-Wittenberg
N.A. Gillespie (Author/Creator) - Virginia Commonwealth University
S.D. Gordon (Author/Creator) - QIMR Berghofer Medical Research Institute
R.F. Gottesman (Author/Creator) - Johns Hopkins University
M.E. Griswold (Author/Creator) - University of Mississippi
V. Gudnason (Author/Creator) - University of Iceland
T.B. Harris (Author/Creator) - National Institutes of Health
A.M. Hartmann (Author/Creator) - Martin Luther University Halle-Wittenberg
A. Hatzimanolis (Author/Creator) - Mental Health Research Institute
G. Heiss (Author/Creator) - University of North Carolina at Chapel Hill
E.G. Holliday (Author/Creator)
P.K. Joshi (Author/Creator) - University of Edinburgh
M. Kähönen (Author/Creator)
S.L.R. Kardia (Author/Creator) - University of Michigan
I. Karlsson (Author/Creator) - Karolinska Institutet
L. Kleineidam (Author/Creator) - University of Bonn
D.S. Knopman (Author/Creator) - Mayo Clinic
N.A. Kochan (Author/Creator) - UNSW Sydney
B. Konte (Author/Creator) - Martin Luther University Halle-Wittenberg
J.B. Kwok (Author/Creator) - UNSW Sydney
S. Le Hellard (Author/Creator) - University of Bergen
T. Lee (Author/Creator) - UNSW Sydney
T. Lehtimäki (Author/Creator)
S-C Li (Author/Creator) - Boston University
T. Liu (Author/Creator) - Max Planck Society
M. Koini (Author/Creator) - Medical University of Graz
E. London (Author/Creator) - University of California, Los Angeles
W.T. Longstreth (Author/Creator) - University of Washington
O.L. Lopez (Author/Creator) - University of Pittsburgh
A. Loukola (Author/Creator) - University of Helsinki
T. Luck (Author/Creator) - Leipzig University
A.J. Lundervold (Author/Creator) - University of Bergen
A. Lundquist (Author/Creator) - Umeå University
L-P Lyytikäinen (Author/Creator)
N.G. Martin (Author/Creator) - QIMR Berghofer Medical Research Institute
G.W. Montgomery (Author/Creator) - The University of Queensland
A.D. Murray (Author/Creator) - University of Edinburgh
A.C. Need (Author/Creator) - Imperial College London
R. Noordam (Author/Creator) - Leiden University
L. Nyberg (Author/Creator) - Umeå University
W. Ollier (Author/Creator) - University of Manchester
G. Papenberg (Author/Creator) - Max Planck Society
A. Pattie (Author/Creator) - University of Edinburgh
O. Polasek (Author/Creator) - University of Split
R.A. Poldrack (Author/Creator) - Stanford University
B.M. Psaty (Author/Creator) - University of Washington
S. Reppermund (Author/Creator) - UNSW Sydney
S.G. Riedel-Heller (Author/Creator) - Leipzig University
R.J. Rose (Author/Creator) - Indiana University
J.I. Rotter (Author/Creator) - University of California, Los Angeles
P. Roussos (Author/Creator) - Icahn School of Medicine at Mount Sinai
S.P. Rovio (Author/Creator) - University of Turku
Y. Saba (Author/Creator) - Medical University of Graz
F.W. Sabb (Author/Creator) - University of Oregon
P.S. Sachdev (Author/Creator) - UNSW Sydney
C.L. Satizabal (Author/Creator) - Boston University
M. Schmid (Author/Creator) - University of Bonn
R.J. Scott (Author/Creator)
M.A. Scult (Author/Creator) - Duke University
J. Simino (Author/Creator) - University of Mississippi
P.E. Slagboom (Author/Creator) - Leiden University
N. Smyrnis (Author/Creator) - Mental Health Research Institute
A. Soumaré (Author/Creator) - Université de Bordeaux
N.C. Stefanis (Author/Creator) - Mental Health Research Institute
D.J. Stott (Author/Creator) - University of Glasgow
R.E. Straub (Author/Creator) - Johns Hopkins University
K. Sundet (Author/Creator) - University of Oslo
A.M. Taylor (Author/Creator) - University of Edinburgh
K.D. Taylor (Author/Creator) - University of California, Los Angeles
I. Tzoulaki (Author/Creator) - Imperial College London
C. Tzourio (Author/Creator) - Université de Bordeaux
A. Uitterlinden (Author/Creator) - Erasmus University Rotterdam
V. Vitart (Author/Creator) - University of Edinburgh
A.N. Voineskos (Author/Creator) - University of Toronto
J. Kaprio (Author/Creator) - Finnish Institute for Health and Welfare
M. Wagner (Author/Creator) - University of Bonn
H. Wagner (Author/Creator) - University of Bonn
L. Weinhold (Author/Creator) - University of Bonn
K.H. Wen (Author/Creator) - Erasmus University Rotterdam
E. Widen (Author/Creator) - University of Helsinki
Q. Yang (Author/Creator) - Boston University
W. Zhao (Author/Creator) - University of Michigan
H.H.H. Adams (Author/Creator) - Erasmus University Rotterdam
D.E. Arking (Author/Creator) - Johns Hopkins University
R.M. Bilder (Author/Creator) - University of California, Los Angeles
P. Bitsios (Author/Creator) - University of Crete
E. Boerwinkle (Author/Creator) - Baylor College of Medicine
O. Chiba-Falek (Author/Creator) - Duke University
A. Corvin (Author/Creator) - Trinity College Dublin
P.L. De Jager (Author/Creator) - Columbia University
S. Debette (Author/Creator) - Université de Bordeaux
G. Donohoe (Author/Creator) - Ollscoil na Gaillimhe – University of Galway
P. Elliott (Author/Creator) - Imperial College London
A.L. Fitzpatrick (Author/Creator) - University of Washington
M. Gill (Author/Creator) - Trinity College Dublin
D.C. Glahn (Author/Creator) - Yale University
S. Hägg (Author/Creator) - Karolinska Institutet
N.K. Hansell (Author/Creator) - The University of Queensland
A.R. Hariri (Author/Creator) - Duke University
M.K. Ikram (Author/Creator)
J.W. Jukema (Author/Creator) - Leiden University
E. Vuoksimaa (Author/Creator) - University of Helsinki
M.C. Keller (Author/Creator) - University of Colorado Boulder
W.S. Kremen (Author/Creator) - University of California San Diego
L. Launer (Author/Creator) - National Institutes of Health
U. Lindenberger (Author/Creator) - Max Planck Society
A. Palotie (Author/Creator) - Wellcome Trust
N.L. Pedersen (Author/Creator) - Karolinska Institutet
N. Pendleton (Author/Creator) - University of Manchester
D.J. Porteous (Author/Creator) - University of Edinburgh
K. Räikkönen (Author/Creator) - University of Helsinki
O.T. Raitakari (Author/Creator) - University of Turku
A. Ramirez (Author/Creator) - University of Bonn
I. Reinvang (Author/Creator) - University of Oslo
I. Rudan (Author/Creator) - University of Edinburgh
D. Rujescu (Author/Creator) - Martin Luther University Halle-Wittenberg
R. Schmidt (Author/Creator) - Medical University of Graz
H. Schmidt (Author/Creator) - Medical University of Graz
P.W. Schofield (Author/Creator)
P.R. Schofield (Author/Creator) - UNSW Sydney
J.M. Starr (Author/Creator) - University of Edinburgh
V.M. Steen (Author/Creator) - University of Bergen
J.N. Trollor (Author/Creator) - UNSW Sydney
S.T. Turner (Author/Creator) - Mayo Clinic
C.M. van Duijn (Author/Creator) - Erasmus University Rotterdam
Arno Villringer (Author/Creator) - Max Planck Society
D.R. Weinberger (Author/Creator) - Johns Hopkins University
D.R. Weir (Author/Creator) - University of Michigan
J.F. Wilson (Author/Creator) - University of Edinburgh
A. Malhotra (Author/Creator) - Hofstra University
A.M. McIntosh (Author/Creator) - University of Edinburgh
C.R. Gale (Author/Creator) - University of Edinburgh
S. Seshadri (Author/Creator) - Boston University
T.H. Mosley (Author/Creator) - University of Mississippi
J. Bressler (Author/Creator) - The University of Texas Health Science Center at Houston
T. Lencz (Author/Creator) - University of Edinburgh
I.J. Deary (Author/Creator) - University of Edinburgh
Publication Details: Nature Communications, Vol.9(1)
Publisher: Springer Nature
Identifiers: 991005542860707891
Copyright: © 2018 Macmillan Publishers Limited, part of Springer Nature
Murdoch Affiliation: School of Engineering and Information Technology
Language: English
Resource Type: Journal article

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