Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions
Year: 2016
Type: article
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 tissue-specific 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.
Source: Translational Psychiatry
DOI: 10.1038/tp.2016.246
Authors: W D Hill, G Davies, S E Harris, S P Hagenaars, The neuroCHARGE Cognitive Working group, Gail Davies, Ian J Deary, Stephanie Debette, Carla I Verbaas, Jan Bressler, Maaike Schuur, Albert V Smith, Joshua C Bis, David A Bennett, M Arfan Ikram, Lenore J Launer, Annette L Fitzpatrick, Sudha Seshadri, Cornelia M van Duijn, Thomas H Mosley Jr, D C Liewald, L Penke, C R Gale, I J Deary
Institutions: University of Edinburgh, Western General Hospital, Institute of Genetics and Cancer, Erasmus MC, Erasmus University Rotterdam, The University of Texas Health Science Center at Houston, Icelandic Heart Association, University of Washington, Rush University Medical Center, National Institutes of Health, National Institute on Aging, Netherlands Consortium for Healthy Ageing, University of Mississippi Medical Center, Leibniz ScienceCampus Primate Cognition, MRC Lifecourse Epidemiology Unit, University of Southampton, University of Göttingen
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,542
Funders: School of Medicine, Boston University, University of Washington, Rush University, University of Texas Health Science Center at Houston, National Institute for Health and Care Research, University of Edinburgh, Institut National de la Santé et de la Recherche Médicale, Háskóli Íslands, Université de Bordeaux, Hjartavernd, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Directorate for Biological Sciences, School of Public Health, University of Texas Health Science Center at Houston, Medical Research Council, Biotechnology and Biological Sciences Research Council, Erasmus Universitair Medisch Centrum Rotterdam, National Institute on Aging, National Institute of Neurological Disorders and Stroke
Awards: G1184531726, G1194337659, UC Davis Alzheimer's Disease Core Center, G1379949353, Centre for Cognitive Ageing & Cognitive Epidemiology, G2352317866, G36433118, G3743240706, G3933842093, G4641403149, Risk Factors, Pathology, and Clinical Expressions of AD, G5067462658, NIHR Senior Investigator Award, G6276181198, G680566116, NIHR Senior Investigator Award, A genome-wide association study of non-pathological cognitive ageing, G828200374, Risk Factors, Pathology, and Clinical Expressions of AD, G983864884
OpenAlex ID: W2951443932