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https://doi.org/10.1038/mp.2014.188
Title: | Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) | Authors: | Davies, G Armstrong, N Bis, J.C |
Keywords: | apolipoprotein E high mobility group N1 protein interleukin 15 transfer RNA high mobility group N1 protein adult Article cell cycle cell death cell survival chromosome 14q chromosome 19q chromosome 21 chromosome 6q cognition cohort analysis cytokine production female gene frequency gene linkage disequilibrium gene location genetic association genetic trait genetic variability genomics genotype phenotype correlation heritability human male middle aged phenotype phenotypic variation priority journal single nucleotide polymorphism aged atherosclerosis cognition Cognition Disorders complication genetic predisposition genetics genome-wide association study meta analysis neuropsychological test physiology Scotland very elderly 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 |
Issue Date: | 2015 | Publisher: | Nature Publishing Group | 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 | Rights: | Attribution 4.0 International | 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. | Source Title: | Molecular Psychiatry | URI: | https://scholarbank.nus.edu.sg/handle/10635/180111 | ISSN: | 1359-4184 | DOI: | 10.1038/mp.2014.188 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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