Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

G. Davies; N. Armstrong; J.C. Bis; J. Bressler; V. Chouraki; S. Giddaluru; E. Hofer; C.A. Ibrahim-Verbaas; M. Kirin; J. Lahti; S.J. van der Lee; S. Le Hellard; T. Liu; R.E. Marioni; C. Oldmeadow; I. Postmus; A.V. Smith; J.A. Smith; A. Thalamuthu; R. Thomson; V. Vitart; J. Wang; L. Yu; L. Zgaga; W. Zhao; R. Boxall; S.E. Harris; W.D. Hill; D.C. Liewald; M. Luciano; H. Adams; D. Ames; N. Amin; P. Amouyel; A.A. Assareh; R. Au; J.T. Becker; A. Beiser; C. Berr; L. Bertram; E. Boerwinkle; B.M. Buckley; H. Campbell; J. Corley; P.L. De Jager; C. Dufouil; J.G. Eriksson; T. Espeseth; J.D. Faul; I. Ford; Generation Scotland; R.F. Gottesman; M.E. Griswold; V. Gudnason; T.B. Harris; G. Heiss; A. Hofman; E.G. Holliday; J. Huffman; S.L.R Kardia; N. Kochan; D.S. Knopman; J.B. Kwok; J-C Lambert; T. Lee; G. Li; S-C Li; M. Loitfelder; O.L. Lopez; A.J. Lundervold; A. Lundqvist; K.A. Mather; S.S. Mirza; L. Nyberg; B.A. Oostra; A. Palotie; G. Papenberg; A. Pattie; K. Petrovic; O. Polasek; B.M. Psaty; P. Redmond; S. Reppermund; J.I. Rotter; H. Schmidt; M. Schuur; P.W. Schofield; R.J. Scott; V.M. Steen; D.J. Stott; J.C. van Swieten; K.D. Taylor; J. Trollor; S. Trompet; A.G. Uitterlinden; G. Weinstein; E. Widen; B.G. Windham; J.W. Jukema; A.F. Wright; M.J. Wright; Q. Yang; H. Amieva; J.R. Attia; D.A Bennett; H. Brodaty; A.J.M. de Craen; C. Hayward; M.A. Ikram; U. Lindenberger; L-G Nilsson; D.J. Porteous; K. Räikkönen; I. Reinvang; I. Rudan; P.S. Sachdev; R. Schmidt; P.R. Schofield; V. Srikanth; J.M. Starr; S.T. Turner; D.R. Weir; J.F. Wilson; C van Duijn; L. Launer; A.L. Fitzpatrick; S. Seshadri; T.H. Mosley; I.J. Deary

doi:10.1038/mp.2014.188

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Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

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Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

G. Davies, N. Armstrong, J.C. Bis, J. Bressler, V. Chouraki, S. Giddaluru, E. Hofer, C.A. Ibrahim-Verbaas, M. Kirin, J. Lahti, …

Molecular Psychiatry, Vol.20(2), pp.183-192

2015

DOI: https://doi.org/10.1038/mp.2014.188

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Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

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Title: Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
Authors/Creators: G. Davies (Author/Creator) - University of Edinburgh
N. Armstrong (Author/Creator) - The University of Sydney
J.C. Bis (Author/Creator) - University of Washington
J. Bressler (Author/Creator) - The University of Texas Health Science Center at Houston
V. Chouraki (Author/Creator) - Boston University
S. Giddaluru (Author/Creator) - University of Bergen
E. Hofer (Author/Creator) - Medical University of Graz
C.A. Ibrahim-Verbaas (Author/Creator) - Erasmus University Rotterdam
M. Kirin (Author/Creator) - University of Edinburgh
J. Lahti (Author/Creator) - University of Helsinki
S.J. van der Lee (Author/Creator) - Erasmus University Rotterdam
S. Le Hellard (Author/Creator) - University of Bergen
T. Liu (Author/Creator) - Max Planck Society
R.E. Marioni (Author/Creator) - University of Edinburgh
C. Oldmeadow (Author/Creator) - University of Newcastle Australia
I. Postmus (Author/Creator) - Leiden University
A.V. Smith (Author/Creator) - University of Iceland
J.A. Smith (Author/Creator) - University of Michigan
A. Thalamuthu (Author/Creator) - UNSW Sydney
R. Thomson (Author/Creator) - University of Tasmania
V. Vitart (Author/Creator) - University of Edinburgh
J. Wang (Author/Creator) - Boston University
L. Yu (Author/Creator) - Rush University Medical Center
L. Zgaga (Author/Creator) - University of Zagreb
W. Zhao (Author/Creator) - University of Michigan
R. Boxall (Author/Creator) - University of Edinburgh
S.E. Harris (Author/Creator) - University of Edinburgh
W.D. Hill (Author/Creator) - University of Edinburgh
D.C. Liewald (Author/Creator) - University of Edinburgh
M. Luciano (Author/Creator) - University of Edinburgh
H. Adams (Author/Creator)
D. Ames (Author/Creator) - The University of Melbourne
N. Amin (Author/Creator) - Erasmus University Rotterdam
P. Amouyel (Author/Creator) - Institut Pasteur
A.A. Assareh (Author/Creator) - UNSW Sydney
R. Au (Author/Creator) - Boston University
J.T. Becker (Author/Creator) - University of Pittsburgh
A. Beiser (Author/Creator) - Boston University
C. Berr (Author/Creator) - Université de Montpellier
L. Bertram (Author/Creator) - Imperial College London
E. Boerwinkle (Author/Creator) - Baylor College of Medicine
B.M. Buckley (Author/Creator) - University College Cork
H. Campbell (Author/Creator) - University of Edinburgh
J. Corley (Author/Creator) - University of Edinburgh
P.L. De Jager (Author/Creator) - Broad Institute
C. Dufouil (Author/Creator) - Inserm
J.G. Eriksson (Author/Creator) - Finnish Institute for Health and Welfare
T. Espeseth (Author/Creator) - University of Oslo
J.D. Faul (Author/Creator) - University of Michigan
I. Ford (Author/Creator) - University of Glasgow
Generation Scotland (Author/Creator) - University of Edinburgh
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
G. Heiss (Author/Creator) - University of North Carolina at Chapel Hill
A. Hofman (Author/Creator) - Erasmus University Rotterdam
E.G. Holliday (Author/Creator) - University of Newcastle Australia
J. Huffman (Author/Creator) - University of Edinburgh
S.L.R Kardia (Author/Creator) - University of Michigan
N. Kochan (Author/Creator) - UNSW Sydney
D.S. Knopman (Author/Creator) - Mayo Clinic
J.B. Kwok (Author/Creator) - UNSW Sydney
J-C Lambert (Author/Creator) - Institut Pasteur
T. Lee (Author/Creator) - UNSW Sydney
G. Li (Author/Creator) - University of Washington
S-C Li (Author/Creator) - Technische Universität Dresden
M. Loitfelder (Author/Creator) - Medical University of Graz
O.L. Lopez (Author/Creator) - University of Pittsburgh
A.J. Lundervold (Author/Creator) - University of Bergen
A. Lundqvist (Author/Creator) - Umeå University
K.A. Mather (Author/Creator) - UNSW Sydney
S.S. Mirza (Author/Creator) - Erasmus University Rotterdam
L. Nyberg (Author/Creator) - Umeå University
B.A. Oostra (Author/Creator) - Erasmus University Rotterdam
A. Palotie (Author/Creator) - University of Helsinki
G. Papenberg (Author/Creator) - Max Planck Society
A. Pattie (Author/Creator) - University of Edinburgh
K. Petrovic (Author/Creator) - Medical University of Graz
O. Polasek (Author/Creator) - University of Split
B.M. Psaty (Author/Creator) - University of Washington
P. Redmond (Author/Creator) - University of Edinburgh
S. Reppermund (Author/Creator) - UNSW Sydney
J.I. Rotter (Author/Creator) - University of California, Los Angeles
H. Schmidt (Author/Creator) - Medical University of Graz
M. Schuur (Author/Creator) - Erasmus University Rotterdam
P.W. Schofield (Author/Creator)
R.J. Scott (Author/Creator) - University of Newcastle Australia
V.M. Steen (Author/Creator) - University of Bergen
D.J. Stott (Author/Creator) - University of Glasgow
J.C. van Swieten (Author/Creator) - Erasmus University Rotterdam
K.D. Taylor (Author/Creator) - University of California, Los Angeles
J. Trollor (Author/Creator) - UNSW Sydney
S. Trompet (Author/Creator) - Leiden University
A.G. Uitterlinden (Author/Creator) - Erasmus University Rotterdam
G. Weinstein (Author/Creator) - Boston University
E. Widen (Author/Creator) - University of Helsinki
B.G. Windham (Author/Creator) - University of Mississippi
J.W. Jukema (Author/Creator) - Leiden University
A.F. Wright (Author/Creator) - University of Edinburgh
M.J. Wright (Author/Creator) - QIMR Berghofer Medical Research Institute
Q. Yang (Author/Creator) - Boston University
H. Amieva (Author/Creator) - Université de Bordeaux
J.R. Attia (Author/Creator) - University of Newcastle Australia
D.A Bennett (Author/Creator) - Rush University Medical Center
H. Brodaty (Author/Creator) - UNSW Sydney
A.J.M. de Craen (Author/Creator) - Leiden University
C. Hayward (Author/Creator) - University of Edinburgh
M.A. Ikram (Author/Creator) - Erasmus University Rotterdam
U. Lindenberger (Author/Creator) - Max Planck Society
L-G Nilsson (Author/Creator) - Umeå University
D.J. Porteous (Author/Creator) - University of Edinburgh
K. Räikkönen (Author/Creator) - University of Helsinki
I. Reinvang (Author/Creator) - University of Oslo
I. Rudan (Author/Creator) - University of Edinburgh
P.S. Sachdev (Author/Creator) - UNSW Sydney
R. Schmidt (Author/Creator) - Medical University of Graz
P.R. Schofield (Author/Creator) - University of Newcastle Australia
V. Srikanth (Author/Creator) - Monash University
J.M. Starr (Author/Creator) - University of Edinburgh
S.T. Turner (Author/Creator) - Mayo Clinic
D.R. Weir (Author/Creator) - University of Michigan
J.F. Wilson (Author/Creator) - University of Edinburgh
C van Duijn (Author/Creator) - Erasmus University Rotterdam
L. Launer (Author/Creator) - National Institutes of Health
A.L. Fitzpatrick (Author/Creator) - University of Washington
S. Seshadri (Author/Creator) - Boston University
T.H. Mosley (Author/Creator) - University of Mississippi
I.J. Deary (Author/Creator) - University of Edinburgh
Publication Details: Molecular Psychiatry, Vol.20(2), pp.183-192
Publisher: Nature Publishing Group
Identifiers: 991005540333307891
Copyright: © 2015 Macmillan Publishers Limited
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.455 Genome-Wide Association Studies
Web Of Science research areas: Biochemistry & Molecular Biology; Neurosciences; Psychiatry
ESI research areas: Neuroscience & Behavior