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Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions

W. D. Hill, G. Davies, S. E Harris, S. P. Hagenaars, The neuroCHARGE Cognitive Working group, D. C. Liewald, L. Penke, C. R. Gale, Ian Deary
doi: https://doi.org/10.1101/063636
W. D. Hill
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
2Department of Psychology, University of Edinburgh, Edinburgh, UK
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G. Davies
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
2Department of Psychology, University of Edinburgh, Edinburgh, UK
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S. E Harris
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
3Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
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S. P. Hagenaars
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
2Department of Psychology, University of Edinburgh, Edinburgh, UK
4Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK
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D. C. Liewald
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
2Department of Psychology, University of Edinburgh, Edinburgh, UK
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L. Penke
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
5Georg Elias Müller Institute of Psychology, Georg August University Göttingen, Germany
6Leibniz Science Campus Primate Cognition, Göttingen, Germany
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C. R. Gale
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
2Department of Psychology, University of Edinburgh, Edinburgh, UK
7MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
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Ian Deary
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
2Department of Psychology, University of Edinburgh, Edinburgh, UK
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Abstract

Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with a 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 and UK Biobank, 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.

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  • Authors for The neuroCHARGE Cognitive Working group found in acknowledgements

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 21, 2016.
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Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions
W. D. Hill, G. Davies, S. E Harris, S. P. Hagenaars, The neuroCHARGE Cognitive Working group, D. C. Liewald, L. Penke, C. R. Gale, Ian Deary
bioRxiv 063636; doi: https://doi.org/10.1101/063636
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Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions
W. D. Hill, G. Davies, S. E Harris, S. P. Hagenaars, The neuroCHARGE Cognitive Working group, D. C. Liewald, L. Penke, C. R. Gale, Ian Deary
bioRxiv 063636; doi: https://doi.org/10.1101/063636

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