Genetic contributions to self-reported tiredness, 2016, Deary et al

Sly Saint

Senior Member (Voting Rights)
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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)"

https://www.biorxiv.org/content/10.1101/047290v1.full
 
Fatigue is a common complaint. In a Dutch adult general population survey with 9375 respondents, 4.9% reported short term fatigue (<6 months duration), 30.5% chronic fatigue (> 6 months duration), and 1% fulfilled diagnostic criteria for Chronic Fatigue Syndrome (CFS) 1.

These findings are similar to a London-based survey of general practice patients in England, aged 18-45, with 15283 respondents, where 36.7% reported substantial fatigue, 18.3% substantial fatigue of > 6 months duration and 1% fulfilled the diagnostic criteria for CFS 2.

Two other large surveys of US workers and community dwelling adults aged 51 and over report fatigue rates of 37.9% (two week period prevalence) and 31.2% (one week period prevalence) respectively 3, 4. In an early review of fatigue epidemiology, Lewis and Wessely5 argue that fatigue “is best viewed on a continuum”, and the continuous distribution of fatigue in the general population is supported by the Pawlikowska et al. study2. Fatigue is also a common presentation in primary care. In a survey of 1428 consultations to 89 GPs in Ireland, fatigue prevalence was 25% and the main reason for attendance in 6.5% 6.
 
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