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

Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Le Hellard, S., Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S. E., Hill, W. D., Liewald, D. C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A. A., Au, R., Becker, J. T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B. M., Campbell, H., Corley, J., De Jager, P. L., Dufouil, C., Eriksson, J. G., Espeseth, T., Faul, J. D., Ford, I., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Heiss, G., Hofman, A., Holliday, E. G., Huffman, J., Kardia, S. L. R., Kochan, N., Knopman, D. S., Kwok, J. B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O. L., Lundervold, A. J., Lundqvist, A., Mather, K. A., Mirza, S. S., Nyberg, L., Oostra, B. A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B. M., Redmond, P., Reppermund, S., Rotter, J. I., Schmidt, H., Schuur, M., Schofield, P. W., Scott, R. J., Steen, V. M., Stott, D. J., Van Swieten, J. C., Taylor, K. D., Trollor, J., Trompet, S., Uitterlinden, A. G., Weinstein, G., Widen, E., Windham, B. G., Jukema, J. W., Wright, A. F., Wright, M. J., Yang, Q., Amieva, H., Attia, J. R., Bennett, D. A., Brodaty, H., de Craen, A. J. M., Hayward, C., Ikram, M. A., Lindenberger, U., Nilsson, L-G, Porteous, D. J., Raikkonen, K., Reinvang, I., Rudan, I., Sachdev, P. S., Schmidt, R., Schofield, P. R., Srikanth, V., Starr, J. M., Turner, S. T., Weir, D. R., Wilson, J. F., Van Duijn, C., Launer, L., Fitzpatrick, A. L., Seshadri, S., Jr, T. H. Mosley and Deary, I. J. (2015) Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949). Molecular Psychiatry, 20 2: 183-192. doi:10.1038/mp.2014.188

Author Davies, G.
Armstrong, N.
Bis, J. C.
Bressler, J.
Chouraki, V.
Giddaluru, S.
Hofer, E.
Ibrahim-Verbaas, C. A.
Kirin, M.
Lahti, J.
van der Lee, S. J.
Le Hellard, S.
Liu, T.
Marioni, R. E.
Oldmeadow, C.
Postmus, I.
Smith, A. V.
Smith, J. A.
Thalamuthu, A.
Thomson, R.
Vitart, V.
Wang, J.
Yu, L.
Zgaga, L.
Zhao, W.
Boxall, R.
Harris, S. E.
Hill, W. D.
Liewald, D. C.
Luciano, M.
Adams, H.
Ames, D.
Amin, N.
Amouyel, P.
Assareh, A. A.
Au, R.
Becker, J. T.
Beiser, A.
Berr, C.
Bertram, L.
Boerwinkle, E.
Buckley, B. M.
Campbell, H.
Corley, J.
De Jager, P. L.
Dufouil, C.
Eriksson, J. G.
Espeseth, T.
Faul, J. D.
Ford, I.
Gottesman, R. F.
Griswold, M. E.
Gudnason, V.
Harris, T. B.
Heiss, G.
Hofman, A.
Holliday, E. G.
Huffman, J.
Kardia, S. L. R.
Kochan, N.
Knopman, D. S.
Kwok, J. B.
Lambert, J-C
Lee, T.
Li, G.
Li, S-C
Loitfelder, M.
Lopez, O. L.
Lundervold, A. J.
Lundqvist, A.
Mather, K. A.
Mirza, S. S.
Nyberg, L.
Oostra, B. A.
Palotie, A.
Papenberg, G.
Pattie, A.
Petrovic, K.
Polasek, O.
Psaty, B. M.
Redmond, P.
Reppermund, S.
Rotter, J. I.
Schmidt, H.
Schuur, M.
Schofield, P. W.
Scott, R. J.
Steen, V. M.
Stott, D. J.
Van Swieten, J. C.
Taylor, K. D.
Trollor, J.
Trompet, S.
Uitterlinden, A. G.
Weinstein, G.
Widen, E.
Windham, B. G.
Jukema, J. W.
Wright, A. F.
Wright, M. J.
Yang, Q.
Amieva, H.
Attia, J. R.
Bennett, D. A.
Brodaty, H.
de Craen, A. J. M.
Hayward, C.
Ikram, M. A.
Lindenberger, U.
Nilsson, L-G
Porteous, D. J.
Raikkonen, K.
Reinvang, I.
Rudan, I.
Sachdev, P. S.
Schmidt, R.
Schofield, P. R.
Srikanth, V.
Starr, J. M.
Turner, S. T.
Weir, D. R.
Wilson, J. F.
Van Duijn, C.
Launer, L.
Fitzpatrick, A. L.
Seshadri, S.
Jr, T. H. Mosley
Deary, I. J.
Title Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
Formatted title
Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
Publication date 2015-02-01
Sub-type Article (original research)
DOI 10.1038/mp.2014.188
Open Access Status DOI
Volume 20
Issue 2
Start page 183
End page 192
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted 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.
Keyword Cognitive function
CHARGE consortium
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 51 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 53 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 29 Mar 2015, 11:03:15 EST by System User on behalf of Scholarly Communication and Digitisation Service