title: Genetic contributions to self-reported tiredness.
abstract: Self-reported tiredness and low energy, often called fatigue, are 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 (GWAS) 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 single-nucleotide polymorphisms for this tiredness question was 8.4% (s.e.=0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 × 10-11). Linkage disequilibrium score regression and polygenic profile score analyses were used to test for shared genetic aetiology between tiredness and up to 29 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and body mass index (BMI), C-reactive protein, high-density lipoprotein (HDL) cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, neuroticism, schizophrenia and verbal-numerical reasoning (absolute rgeffect sizes between 0.02 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, low-density lipoprotein cholesterol, coronary artery disease, C-reactive protein, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder and schizophrenia (standardised β's had absolute values<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.
authors.affiliation: Department of Psychology, Northumbria University, Newcastle, UK.
authors.forename: V
authors.initials: V
authors.lastname: Deary
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Hagenaars
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh, Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: W D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.affiliation: Department of Psychology, Northumbria University, Newcastle, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: D C M
authors.initials: DCM
authors.lastname: Liewald
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Gale
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000328:Adult; D000368:Aged; D000075368:Anoctamins / Q000235:genetics; D015992:Body Mass Index; D005221:Fatigue / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D008875:Middle Aged; D020412:Multifactorial Inheritance; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012307:Risk Factors; D057566:Self Report; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom; D012097:Repressor Proteins
chemical_list: D000075368:Anoctamins; D017448:Receptors, Dopamine D2; D014157:Transcription Factors; C000594870:ANO10 protein, human; C494423:ASXL3 protein, human; D012097:Repressor Proteins; C581293:DRD2 protein, human