UNIVERSITY OF EDINBURGH London research found small genetic contributions to self-reported tiredness and low energy

Already feeling drained so early in the year? Genes might contribute in a small but significant way to whether people report being tired and low in energy. This is according to UK researchers led by Vincent Deary of Northumbria University, Newcastle, and Saskia Hagenaars of the University of Edinburgh, in a paper in Springer Nature’s journal Molecular Psychiatry.

They found that genetics accounts for about eight percent of people’s differences in self-reported tiredness/low energy; this implies that the vast majority of people’s differences in self-reported tiredness are environmental in origin. The researchers found that the small genetic contributions to self-reported tiredness overlapped with genetic contributions to a range of mental and physical health conditions, and with whether people smoke, or are carrying too much weight, and also longevity.

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), researchers 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 rg 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<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.

Their large-scale study analyzed genetic information of 111,749 participants who all indicated whether they felt tired or low in energy in the two weeks before their data were collected in the UK Biobank study. The large UK Biobank resource is used to identify the reasons behind certain diseases occurring in middle aged and older people. It includes genetic samples as well as information about participants’ physical and mental health, personality and cognitive functioning. The researchers working together on the study conducted various statistical analyses, including genome-wide associations, heritability estimates, and testing genetic associations between tiredness and more than 25 health-related variables. The researchers took factors such as age and gender into account.

The findings suggest that it was genetic proneness to some illnesses, not just presence of these illnesses, that had an association with self-reports of tiredness. For instance, the researchers looked at people who were genetically prone to diabetes but did not have the condition, and the small genetic link with tiredness remained intact. Indeed, genetic overlap was found to exist between tiredness and a general tendency to poor health.

Tiredness partly genetic say researchers

Genes may contribute in a small but significant way to why certain people tire easily or suffer from low energy levels.

Being prone to tiredness is partly heritable, according to researchers, with genetics accounting for eight per cent of differences between people who were asked about their levels of tiredness.

Large sample

The large-scale study was led by Saskia Hagenaars, a PhD student at the University of Edinburgh’s Centre for Cognitive Ageing and Cognitive Epidemiology and Dr Vincent Deary of Northumbria University.

They analyzed genetic make-up from 111,749 participants who had reported whether they whether they had felt tired or had low energy in the two weeks before data was collected for the UK Biobank.

Genetic overlap

Researchers also found that the genetic predisposition to tiredness was often present in people genetically prone to a range of mental and physical health conditions, such as smoking, depression and schizophrenia.

A genetic overlap was also identified between low energy levels, and high cholesterol levels and obesity.

According to the researchers, this raises the possibility of a genetic link between tiredness and a vulnerability to physiological stress.

Environmental factors

In general, the genetic overlap was found to exist between tiredness and a general tendency to poor health.

Most of people’s differences in tiredness are probably environmental, the researchers say. The genetic data accounted for only 8.4 percent of people’s differences in tiredness.

The findings are published in a paper, Genetic contributions to self-reported tiredness, in the journal Molecular Psychiatry.

Some people report feeling generally more wabbit or puggled than others. Our results suggest that a small but detectable part of that variation is related to differences in people’s genes. And the genes involved are associated with a range of health and personality factors.

Professor Ian DearyLeader of the research team



Molecular Psychiatry advance online publication, 14 February 2017; doi:10.1038/mp.2017.5.

National Institute of Health



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