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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=53949).
Friday,2015-08-28 11:58 America/Los_Angeles — zdrager
| Title | Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Davies, G, Armstrong, N, Bis, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, van der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N, Knopman, DS, Kwok, JB, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, van Swieten, JC, Taylor, KD, Trollor, J, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, Wright, AF, Wright, MJ, Yang, Q, Amieva, H, Attia, JR, Bennett, DA, Brodaty, H, de Craen, AJM, Hayward, C, Ikram, MA, Lindenberger, U, Nilsson, L-G, Porteous, DJ, Räikkönen, K, Reinvang, I, Rudan, I, Sachdev, PS, Schmidt, R, Schofield, PR, Srikanth, V, Starr, JM, Turner, ST, Weir, DR, Wilson, JF, van Duijn, C, Launer, L, Fitzpatrick, AL, Seshadri, S, Mosley, TH, Deary, IJ |
| Corporate/Institutional Authors | Generation Scotland |
| Journal | Mol Psychiatry |
| Volume | 20 |
| Issue | 2 |
| Pagination | 183-92 |
| Date Published | 2015 Feb |
| ISSN | 1476-5578 |
| Keywords | Aged, Aged, 80 and over, Atherosclerosis, Cognition, Cognition Disorders, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HMGN1 Protein, Humans, Male, Middle Aged, Neuropsychological Tests, Phenotype, Polymorphism, Single Nucleotide, Scotland |
| Abstract | <p>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.</p> |
| DOI | 10.1038/mp.2014.188 |
| Alternate Journal | Mol. Psychiatry |
| PubMed ID | 25644384 |
| PubMed Central ID | PMC4356746 |
| Grant List | BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom CZB/4/505 / / Chief Scientist Office / United Kingdom CZB/4/710 / / Chief Scientist Office / United Kingdom CZD/16/6/4 / / Chief Scientist Office / United Kingdom ETM/55 / / Chief Scientist Office / United Kingdom G0700704 / / Medical Research Council / United Kingdom MC_PC_U127561128 / / Medical Research Council / United Kingdom MR/K026992/1 / / Medical Research Council / United Kingdom P30 AG010161 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States S18386 / / Biotechnology and Biological Sciences Research Council / United Kingdom U01 AG049505 / AG / NIA NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1 TR000135 / TR / NCATS NIH HHS / United States |