Please use this identifier to cite or link to this item: https://doi.org/10.1038/tp.2016.246
Title: Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions
Authors: Hill, W.D
Davies, G
Harris, S.E
Hagenaars, S.P
Liewald, D.C
Penke, L
Gale, C.R
Deary, I.J
Debette, S
Verbaas, C.I
Bressler, J
Schuur, M
Smith, A.V
Bis, J.C
Bennett, D.A
Ikram, M.A 
Launer, L.J
Fitzpatrick, A.L
Seshadri, S
Van Duijn, C.M
Mosley, T.H
Keywords: histone
Article
biobank
cognition
gene linkage disequilibrium
genome
genome-wide association study
molecular genetics
pleiotropy
single nucleotide polymorphism
aged
brain
cognition
conserved sequence
female
genetic variation
genetics
human
male
middle aged
molecular biology
molecular evolution
neuropsychological test
phenotype
physiology
problem solving
statistics
Aged
Brain
Cognition
Conserved Sequence
Evolution, Molecular
Female
Genetic Variation
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Male
Middle Aged
Molecular Biology
Neuropsychological Tests
Phenotype
Polymorphism, Single Nucleotide
Problem Solving
Statistics as Topic
Issue Date: 2016
Publisher: Springer Nature
Citation: Hill, W.D, Davies, G, Harris, S.E, Hagenaars, S.P, Liewald, D.C, Penke, L, Gale, C.R, Deary, I.J, Debette, S, Verbaas, C.I, Bressler, J, Schuur, M, Smith, A.V, Bis, J.C, Bennett, D.A, Ikram, M.A, Launer, L.J, Fitzpatrick, A.L, Seshadri, S, Van Duijn, C.M, Mosley, T.H (2016). Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions. Translational Psychiatry 6 (12) : e980. ScholarBank@NUS Repository. https://doi.org/10.1038/tp.2016.246
Rights: Attribution 4.0 International
Abstract: Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n =53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissuespecific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ?2.6% of the SNPs from each GWAS but accounted for ? 40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions. © The Author(s) 2016.
Source Title: Translational Psychiatry
URI: https://scholarbank.nus.edu.sg/handle/10635/183585
ISSN: 2158-3188
DOI: 10.1038/tp.2016.246
Rights: Attribution 4.0 International
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