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Genetic contributions to self-reported tiredness

Vincent Deary, Saskia P Hagenaars, Sarah E Harris, W David Hill, Gail Davies, David CM Liewald, International Consortium for Blood Pressure GWAS, CHARGE consortium Aging and Longevity Group, Andrew M McIntosh, Catharine R Gale, Ian J Deary
doi: https://doi.org/10.1101/047290
Vincent Deary
1Department of Psychology, Northumbria University, Newcastle, NE1 8ST, UK
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  • For correspondence: vincent.deary@northumbria.ac.uk ian.deary@ed.ac.uk
Saskia P Hagenaars
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
3Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK
4Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK
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Sarah E Harris
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
5Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
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W David Hill
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
3Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK
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Gail Davies
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
3Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK
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David CM Liewald
1Department of Psychology, Northumbria University, Newcastle, NE1 8ST, UK
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
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Andrew M McIntosh
4Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK
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Catharine R Gale
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
3Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK
6MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK
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Ian J Deary
2Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
3Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK
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  • For correspondence: vincent.deary@northumbria.ac.uk ian.deary@ed.ac.uk
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Abstract

Self-reported tiredness and low energy, often called fatigue, is associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6% and 50%. In the UK Biobank sample (N = 108 976) we carried out a genome-wide association study of responses to the question, “Over the last two weeks, how often have you felt tired or had little energy?” Univariate GCTA-GREML found that the proportion of variance explained by all common SNPs for this tiredness question was 8.4% (SE = 0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; p = 1.36 x 10-11). LD score regression and polygenic profile analysis were used to test for pleiotropy between tiredness and up to 28 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and BMI, HDL cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, ADHD, bipolar disorder, major depressive disorder, neuroticism, schizophrenia, and verbal-numerical reasoning (absolute rg effect sizes between 0.11 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, LDL cholesterol, coronary artery disease, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, and waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder, and schizophrenia (standardised β’s between −0.016 and 0.03). These results suggest that tiredness is a partly-heritable, heterogeneous and complex phenomenon that is phenotypically and genetically associated with affective, cognitive, personality, and physiological processes.

“Hech, sirs! But I’m wabbit, I’m back frae the toon;

I ha’ena dune pechin’—jist let me sit doon.

From Glesca’

By William Dixon Cocker (1882-1970)

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Posted April 05, 2016.
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Genetic contributions to self-reported tiredness
Vincent Deary, Saskia P Hagenaars, Sarah E Harris, W David Hill, Gail Davies, David CM Liewald, International Consortium for Blood Pressure GWAS, CHARGE consortium Aging and Longevity Group, Andrew M McIntosh, Catharine R Gale, Ian J Deary
bioRxiv 047290; doi: https://doi.org/10.1101/047290
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Genetic contributions to self-reported tiredness
Vincent Deary, Saskia P Hagenaars, Sarah E Harris, W David Hill, Gail Davies, David CM Liewald, International Consortium for Blood Pressure GWAS, CHARGE consortium Aging and Longevity Group, Andrew M McIntosh, Catharine R Gale, Ian J Deary
bioRxiv 047290; doi: https://doi.org/10.1101/047290

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