Dataset Information

Investigating causality in the association between vitamin D status and self-reported tiredness.

ABSTRACT: Self-reported tiredness or low energy, often referred to as fatigue, has been linked to low levels of circulating 25-hydroxyvitamin D (25OHD), a biomarker of vitamin D status. Although it is uncertain if the association is causal, fatigue is a common indication for testing, and correcting, low 25OHD-levels. We used two-sample Mendelian randomization to test for genetic evidence of a causal association between low 25OHD-levels and fatigue. Genetic-25OHD associations were estimated from the largest genome-wide association study of vitamin D to date, and genetic-fatigue associations were estimated in 327,478 individuals of European descent in UK Biobank, of whom 19,526 (5.96%) reported fatigue (tiredness or low energy nearly every day over the past two weeks). Using seven genome-wide significant 25OHD-reducing genetic variants, there was little evidence for a causal effect of 25OHD on fatigue (odds ratio for fatigue was 1.05 with 95% confidence interval of 0.87-1.27 per 1-SD decrease in log-transformed 25OHD). There was also little evidence of association between any individual 25OHD-reducing variant and fatigue. Our results suggest that a clinically relevant protective effect of 25OHD-levels on fatigue is unlikely. Therefore, vitamin D supplementation of the general population to raise 25OHD-levels is not likely to be useful in preventing fatigue.

SUBMITTER: Havdahl A

PROVIDER: S-EPMC6393455 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Investigating causality in the association between vitamin D status and self-reported tiredness.

Havdahl Alexandra A Mitchell Ruth R Paternoster Lavinia L Davey Smith George G

Scientific reports 20190227 1

Self-reported tiredness or low energy, often referred to as fatigue, has been linked to low levels of circulating 25-hydroxyvitamin D (25OHD), a biomarker of vitamin D status. Although it is uncertain if the association is causal, fatigue is a common indication for testing, and correcting, low 25OHD-levels. We used two-sample Mendelian randomization to test for genetic evidence of a causal association between low 25OHD-levels and fatigue. Genetic-25OHD associations were estimated from the larges ...[more]

PMID: 30814568

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Project description: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 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.

Project description:BackgroundPhysical activity (PA) was strongly associated with health status, with fewer related studies in adolescents (12-19 years). Most current studies using questionnaires to assess PA levels were not objective enough. So, this study used a wearable device to assess PA levels quantitatively and focused on the association between PA levels and self-reported 4 health status among adolescents.MethodsData were obtained from adolescents (2241) with both PA and health status assessments from two cycles of NHANES, 2011-2014, using a wearable accelerometer-based device to assess PA levels quantitatively, MIMS-units as the metric, averaging over all valid days of wear (MIMS-units average). There were 4 health statuses, including (1) whether or not flu, pneumonia, or ear infection, (2) whether or not stomach or intestinal illness, (3) whether or not head cold or chest cold, and (4) general health condition, from the past 30 days self-reported. Weighted multiple logistic regression was used to analyze the association between the 4 health statuses and the MIMS-units average and MIMS-units average quartiles respectively. Subgroup analyses were also conducted on age, sex, BMI, and race.ResultsAfter controlling confounding factors, there was no significant correlation between the MIMS-units average and the four physical health conditions in Table 3 model 3. While MIMS-units average quartiles results showed that compared to lower PA levels (Q1), higher PA levels (Q4) were linked to a lower incidence of "flu"(OR = 0.94, 95% CI [0.91, 0.99], P < 0.001). Furthermore, Q3 was linked to a decrease in the incidence of "head cold" (OR = 0.91, 95% CI [0.85, 0.96], P < 0.001), while Q2 showed a decrease in "stomach illness" (OR = 0.95, 95% CI [0.92, 0.99], P = 0.003) in Table 3 model 3. Subgroup analyses showed that higher PA levels significantly reduced "flu" risk among 12-15 year-olds, girls, obese, and Non-Hispanic White; decreased "head cold" risk among 16-19 year-olds, boys, obese, and Non-Hispanic White; significantly lower risk of "stomach illness" in girls.ConclusionsEnhancing PA levels can help prevent flu, head cold, and stomach or intestinal illness in US adolescents. Further studies are needed to determine whether adolescents in other regions have similar results, and high-quality cohort studies are needed to further validate the causal association.

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Investigating causality in the association between vitamin D status and self-reported tiredness.

Publications

Investigating causality in the association between vitamin D status and self-reported tiredness.

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