@article{42b15a6f41294618ba6a5551f43d676d,
title = "Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)",
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.",
author = "G. Davies and N. Armstrong and Bis, {J. C.} and J. Bressler and V. Chouraki and S. Giddaluru and E. Hofer and Ibrahim-Verbaas, {C. A.} and M. Kirin and J. Lahti and {Van Der Lee}, {S. J.} and {Le Hellard}, S. and T. Liu and Marioni, {R. E.} and C. Oldmeadow and I. Postmus and Smith, {A. V.} and Smith, {J. A.} and A. Thalamuthu and R. Thomson and V. Vitart and J. Wang and L. Yu and L. Zgaga and W. Zhao and R. Boxall and Harris, {S. E.} and Hill, {W. D.} and Liewald, {D. C.} and M. Luciano and H. Adams and D. Ames and N. Amin and P. Amouyel and Assareh, {A. A.} and R. Au and Becker, {J. T.} and A. Beiser and C. Berr and L. Bertram and E. Boerwinkle and Buckley, {B. M.} and H. Campbell and J. Corley and {De Jager}, {P. L.} and C. Dufouil and Eriksson, {J. G.} and T. Espeseth and Faul, {J. D.} and I. Ford and Generation Scotland and Gottesman, {R. F.} and Griswold, {M. E.} and V. Gudnason and Harris, {T. B.} and G. Heiss and A. Hofman and Holliday, {E. G.} and J. Huffman and Kardia, {S. L.R.} and N. Kochan and Knopman, {D. S.} and Kwok, {J. B.} and Lambert, {J. C.} and T. Lee and G. Li and Li, {S. C.} and M. Loitfelder and Lopez, {O. L.} and Lundervold, {A. J.} and A. Lundqvist and Mather, {K. A.} and Mirza, {S. S.} and L. Nyberg and Oostra, {B. A.} and A. Palotie and G. Papenberg and A. Pattie and K. Petrovic and O. Polasek and Psaty, {B. M.} and P. Redmond and S. Reppermund and Rotter, {J. I.} and H. Schmidt and M. Schuur 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 J. Trollor and S. Trompet and Uitterlinden, {A. G.} and G. Weinstein and E. Widen and Windham, {B. G.} and Jukema, {J. W.} and Wright, {A. F.} and Wright, {M. J.} and Q. Yang and H. Amieva and Attia, {J. R.} and Bennett, {D. A.} and H. Brodaty and {De Craen}, {A. J.M.} and C. Hayward and Ikram, {M. A.} and U. Lindenberger and Nilsson, {L. G.} and Porteous, {D. J.} and K. R{\"a}ikk{\"o}nen and I. Reinvang and I. Rudan and Sachdev, {P. S.} and R. Schmidt and Schofield, {P. R.} and V. Srikanth and Starr, {J. M.} and Turner, {S. T.} and Weir, {D. R.} and Wilson, {J. F.} and {Van Duijn}, C. and L. Launer and Fitzpatrick, {A. L.} and S. Seshadri and Mosley, {T. H.} and Deary, {I. J.} and {CHARGE Consortium}",
year = "2015",
month = feb,
day = "1",
doi = "10.1038/mp.2014.188",
language = "English",
volume = "20",
pages = "183--192",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "2",
}