Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

Davies, G. and Armstrong, N. and Bis, J. C. and Bressler, J. and Chouraki, V. and Giddaluru, S. and Hofer, E. and Ibrahim-Verbaas, C. A. and Kirin, M. and Lahti, J. and van der Lee, S. J. and Le Hellard, S. and Liu, T. and Marioni, R. E. and Oldmeadow, C. and Postmus, I. and Smith, A. V. and Smith, J. A. and Thalamuthu, A. and Thomson, R. and Vitart, V. and Wang, J. and Yu, L. and Zgaga, Lina and Zhao, W. and Boxall, R. and Harris, S. E. and Hill, W. D. and Liewald, D. C. and Luciano, M. and Adams, H. and Ames, D. and Amin, N. and Amouyel, P. and Assareh, A. A. and Au, R. and Becker, J. T. and Beiser, A. and Berr, C. and Bertram, L. and Boerwinkle, E. and Buckley, B. M. and Campbell, H. and Corley, J. and De Jager, P. L. and Dufouil, C. and Eriksson, J. G. and Espeseth, T. and Faul, J. D. and Ford, I. and Gottesman, R. F. and Griswold, M. E. and Gudnason, V. and Harris, T. B. and Heiss, G. and Hofman, A. and Holliday, E. G. and Huffman, J. and Kardia, S. L. R. and Kochan, N. and Knopman, D. S. and Kwok, J. B. and Lambert, J.-C. and Lee, T. and Li, G. and Li, S.-C. and Loitfelder, M. and Lopez, O. L. and Lundervold, A. J. and Lundqvist, A. and Mather, K. A. and Mirza, S. S. and Nyberg, L. and Oostra, B. A. and Palotie, A. and Papenberg, G. and Pattie, A. and Petrovic, K. and Polašek, Ozren and Psaty, B. M. and Redmond, P. and Reppermund, S. and Rotter, J. I. and Schmidt, H. and Schuur, M. and Schofield, P. W. and Scott, R. J. and Steen, V. M. and Stott, D. J. and van Swieten, J. C. and Taylor, K. D. and Trollor, J. and Trompet, S. and Uitterlinden, A. G. and Weinstein, G. and Widen, E. and Windham, B. G. and Jukema, J. Wouter and Wright, A. F. and Wright, M. J. and Yang, Q. and Amieva, H. and Attia, J. R. and Bennett, D. A. and Brodaty, H. and de Craen, A. J. M. and Hayward, C. and Ikram, M. A. and Lindenberger, U. and Nilsson, L.-G. and Porteous, D. J. and Räikkönen, K. and Reinvang, I. and Rudan, Igor and Sachdev, P. S. and Schmidt, R. and Schofield, P. R. and Srikanth, V. and Starr, J. M. and Turner, S. T. and Weir, D. R. and Wilson, J. F. and van Duijn, C. and Launer, L. and Fitzpatrick, A. L. and Seshadri, S. and Mosley, T. H. 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=53949). Molecular Psychiatry, 20 (2). pp. 183-92. ISSN 1476-5578

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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.

Item Type: Article
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Departments: Katedra za medicinsku statistiku, epidemiologiju i medicinsku informatiku
Depositing User: Marijan Šember
Status: Published
Creators:
CreatorsEmail
Davies, G.UNSPECIFIED
Armstrong, N.UNSPECIFIED
Bis, J. C.UNSPECIFIED
Bressler, J.UNSPECIFIED
Chouraki, V.UNSPECIFIED
Giddaluru, S.UNSPECIFIED
Hofer, E.UNSPECIFIED
Ibrahim-Verbaas, C. A.UNSPECIFIED
Kirin, M.UNSPECIFIED
Lahti, J.UNSPECIFIED
van der Lee, S. J.UNSPECIFIED
Le Hellard, S.UNSPECIFIED
Liu, T.UNSPECIFIED
Marioni, R. E.UNSPECIFIED
Oldmeadow, C.UNSPECIFIED
Postmus, I.UNSPECIFIED
Smith, A. V.UNSPECIFIED
Smith, J. A.UNSPECIFIED
Thalamuthu, A.UNSPECIFIED
Thomson, R.UNSPECIFIED
Vitart, V.UNSPECIFIED
Wang, J.UNSPECIFIED
Yu, L.UNSPECIFIED
Zgaga, LinaUNSPECIFIED
Zhao, W.UNSPECIFIED
Boxall, R.UNSPECIFIED
Harris, S. E.UNSPECIFIED
Hill, W. D.UNSPECIFIED
Liewald, D. C.UNSPECIFIED
Luciano, M.UNSPECIFIED
Adams, H.UNSPECIFIED
Ames, D.UNSPECIFIED
Amin, N.UNSPECIFIED
Amouyel, P.UNSPECIFIED
Assareh, A. A.UNSPECIFIED
Au, R.UNSPECIFIED
Becker, J. T.UNSPECIFIED
Beiser, A.UNSPECIFIED
Berr, C.UNSPECIFIED
Bertram, L.UNSPECIFIED
Boerwinkle, E.UNSPECIFIED
Buckley, B. M.UNSPECIFIED
Campbell, H.UNSPECIFIED
Corley, J.UNSPECIFIED
De Jager, P. L.UNSPECIFIED
Dufouil, C.UNSPECIFIED
Eriksson, J. G.UNSPECIFIED
Espeseth, T.UNSPECIFIED
Faul, J. D.UNSPECIFIED
Ford, I.UNSPECIFIED
Gottesman, R. F.UNSPECIFIED
Griswold, M. E.UNSPECIFIED
Gudnason, V.UNSPECIFIED
Harris, T. B.UNSPECIFIED
Heiss, G.UNSPECIFIED
Hofman, A.UNSPECIFIED
Holliday, E. G.UNSPECIFIED
Huffman, J.UNSPECIFIED
Kardia, S. L. R.UNSPECIFIED
Kochan, N.UNSPECIFIED
Knopman, D. S.UNSPECIFIED
Kwok, J. B.UNSPECIFIED
Lambert, J.-C.UNSPECIFIED
Lee, T.UNSPECIFIED
Li, G.UNSPECIFIED
Li, S.-C.UNSPECIFIED
Loitfelder, M.UNSPECIFIED
Lopez, O. L.UNSPECIFIED
Lundervold, A. J.UNSPECIFIED
Lundqvist, A.UNSPECIFIED
Mather, K. A.UNSPECIFIED
Mirza, S. S.UNSPECIFIED
Nyberg, L.UNSPECIFIED
Oostra, B. A.UNSPECIFIED
Palotie, A.UNSPECIFIED
Papenberg, G.UNSPECIFIED
Pattie, A.UNSPECIFIED
Petrovic, K.UNSPECIFIED
Polašek, OzrenUNSPECIFIED
Psaty, B. M.UNSPECIFIED
Redmond, P.UNSPECIFIED
Reppermund, S.UNSPECIFIED
Rotter, J. I.UNSPECIFIED
Schmidt, H.UNSPECIFIED
Schuur, M.UNSPECIFIED
Schofield, P. W.UNSPECIFIED
Scott, R. J.UNSPECIFIED
Steen, V. M.UNSPECIFIED
Stott, D. J.UNSPECIFIED
van Swieten, J. C.UNSPECIFIED
Taylor, K. D.UNSPECIFIED
Trollor, J.UNSPECIFIED
Trompet, S.UNSPECIFIED
Uitterlinden, A. G.UNSPECIFIED
Weinstein, G.UNSPECIFIED
Widen, E.UNSPECIFIED
Windham, B. G.UNSPECIFIED
Jukema, J. WouterUNSPECIFIED
Wright, A. F.UNSPECIFIED
Wright, M. J.UNSPECIFIED
Yang, Q.UNSPECIFIED
Amieva, H.UNSPECIFIED
Attia, J. R.UNSPECIFIED
Bennett, D. A.UNSPECIFIED
Brodaty, H.UNSPECIFIED
de Craen, A. J. M.UNSPECIFIED
Hayward, C.UNSPECIFIED
Ikram, M. A.UNSPECIFIED
Lindenberger, U.UNSPECIFIED
Nilsson, L.-G.UNSPECIFIED
Porteous, D. J.UNSPECIFIED
Räikkönen, K.UNSPECIFIED
Reinvang, I.UNSPECIFIED
Rudan, IgorUNSPECIFIED
Sachdev, P. S.UNSPECIFIED
Schmidt, R.UNSPECIFIED
Schofield, P. R.UNSPECIFIED
Srikanth, V.UNSPECIFIED
Starr, J. M.UNSPECIFIED
Turner, S. T.UNSPECIFIED
Weir, D. R.UNSPECIFIED
Wilson, J. F.UNSPECIFIED
van Duijn, C.UNSPECIFIED
Launer, L.UNSPECIFIED
Fitzpatrick, A. L.UNSPECIFIED
Seshadri, S.UNSPECIFIED
Mosley, T. H.UNSPECIFIED
Deary, I. J.UNSPECIFIED
Date: February 2015
Date Deposited: 08 Feb 2016 12:39
Last Modified: 08 Feb 2016 12:39
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/2415

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