@article {Deary047290, author = {Vincent Deary and Saskia P Hagenaars and Sarah E Harris and W David Hill and Gail Davies and David CM Liewald and International Consortium for Blood Pressure GWAS and CHARGE consortium Aging and Longevity Group and Andrew M McIntosh and Catharine R Gale and Ian J Deary}, title = {Genetic contributions to self-reported tiredness}, elocation-id = {047290}, year = {2016}, doi = {10.1101/047290}, publisher = {Cold Spring Harbor Laboratory}, 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, {\textquotedblleft}Over the last two weeks, how often have you felt tired or had little energy?{\textquotedblright} 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{\textquoteright}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.{\textquotedblleft}Hech, sirs! But I{\textquoteright}m wabbit, I{\textquoteright}m back frae the toon;I ha{\textquoteright}ena dune pechin{\textquoteright}{\textemdash}jist let me sit doon.From Glesca{\textquoteright}By William Dixon Cocker (1882-1970)}, URL = {https://www.biorxiv.org/content/early/2016/04/05/047290}, eprint = {https://www.biorxiv.org/content/early/2016/04/05/047290.full.pdf}, journal = {bioRxiv} }