Genetic contributions to self-reported tiredness

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...

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Bibliographic Details
Published in:Molecular psychiatry 2018-03, Vol.23 (3), p.609-620
Main Authors: Deary, V, Hagenaars, S P, Harris, S E, Hill, W D, Davies, G, Liewald, D C M, McIntosh, A M, Gale, C R, Deary, I J
Format: Article
Language:English
Subjects:
Adult
Aged
Anoctamins - genetics
Attention deficit hyperactivity disorder
Bipolar disorder
Body mass
Body Mass Index
C-reactive protein
Cardiovascular disease
Children
Cholesterol
Cognitive ability
Coronary artery
Coronary artery disease
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Fatigue
Fatigue - genetics
Fatigue - physiopathology
Female
Genetic aspects
Genetic Predisposition to Disease
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Genotypes
Grip strength
Health aspects
Heart diseases
Heritability
High density lipoprotein
Hip
Humans
Linkage disequilibrium
Linkage Disequilibrium - genetics
Low density lipoprotein
Male
Mental depression
Mental disorders
Mental Disorders - genetics
Mental health
Methods
Middle Aged
Multifactorial Inheritance
Neurosis
Obesity
Obesity - genetics
Original
Polygenic inheritance
Polymorphism, Single Nucleotide - genetics
Receptors, Dopamine D2 - genetics
Risk Factors
Schizophrenia
Self Report
Single-nucleotide polymorphism
Smoking
Statistics, Nonparametric
Transcription Factors - genetics
Triglycerides
United Kingdom
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Summary: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 ). 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 r effect 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
ISSN:1359-4184
1476-5578
DOI:10.1038/mp.2017.5