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https://doi.org/10.1038/mp.2014.188
DC Field | Value | |
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dc.title | Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) | |
dc.contributor.author | Davies, G | |
dc.contributor.author | Armstrong, N | |
dc.contributor.author | Bis, J.C | |
dc.date.accessioned | 2020-10-26T07:00:43Z | |
dc.date.available | 2020-10-26T07:00:43Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Davies, G, Armstrong, N, Bis, J.C (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. ScholarBank@NUS Repository. https://doi.org/10.1038/mp.2014.188 | |
dc.identifier.issn | 1359-4184 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/180111 | |
dc.description.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. © 2015 Macmillan Publishers Limited. | |
dc.publisher | Nature Publishing Group | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | apolipoprotein E | |
dc.subject | high mobility group N1 protein | |
dc.subject | interleukin 15 | |
dc.subject | transfer RNA | |
dc.subject | high mobility group N1 protein | |
dc.subject | adult | |
dc.subject | Article | |
dc.subject | cell cycle | |
dc.subject | cell death | |
dc.subject | cell survival | |
dc.subject | chromosome 14q | |
dc.subject | chromosome 19q | |
dc.subject | chromosome 21 | |
dc.subject | chromosome 6q | |
dc.subject | cognition | |
dc.subject | cohort analysis | |
dc.subject | cytokine production | |
dc.subject | female | |
dc.subject | gene frequency | |
dc.subject | gene linkage disequilibrium | |
dc.subject | gene location | |
dc.subject | genetic association | |
dc.subject | genetic trait | |
dc.subject | genetic variability | |
dc.subject | genomics | |
dc.subject | genotype phenotype correlation | |
dc.subject | heritability | |
dc.subject | human | |
dc.subject | male | |
dc.subject | middle aged | |
dc.subject | phenotype | |
dc.subject | phenotypic variation | |
dc.subject | priority journal | |
dc.subject | single nucleotide polymorphism | |
dc.subject | aged | |
dc.subject | atherosclerosis | |
dc.subject | cognition | |
dc.subject | Cognition Disorders | |
dc.subject | complication | |
dc.subject | genetic predisposition | |
dc.subject | genetics | |
dc.subject | genome-wide association study | |
dc.subject | meta analysis | |
dc.subject | neuropsychological test | |
dc.subject | physiology | |
dc.subject | Scotland | |
dc.subject | very elderly | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Atherosclerosis | |
dc.subject | Cognition | |
dc.subject | Cognition Disorders | |
dc.subject | Cohort Studies | |
dc.subject | Female | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Genome-Wide Association Study | |
dc.subject | HMGN1 Protein | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Middle Aged | |
dc.subject | Neuropsychological Tests | |
dc.subject | Phenotype | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Scotland | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1038/mp.2014.188 | |
dc.description.sourcetitle | Molecular Psychiatry | |
dc.description.volume | 20 | |
dc.description.issue | 2 | |
dc.description.page | 183-192 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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