The Effect of Socioeconomic Deprivation on the Association between an Extended Lifestyle Score and Health Outcomes in the UK Biobank Cohort

Preliminary reports suggest that the Coronavirus Disease 2019 (COVIDâ^’19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. The extent to which these disparities are related to socioeconomic versus biologic factors is largely unknown. We investigate the racial and socioeconomic associations of COVIDâ^’19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both black participants (odds ratio 3.4; 95%CI 2.4â^’4.9) and Asian participants (odds ratio 2.1; 95%CI 1.5â^’3.2) were at substantially increased risk as compared to white participants. We further observed a striking gradient in COVIDâ^’19 hospitalization rates according to the Townsend Deprivation Index â^’ a composite measure of socioeconomic deprivation â^’ and household income. Adjusting for such factors led to only modest attenuation of the increased risk in black participants, adjusted odds ratio 3.1 (95%CI 2.0â^’4.8). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-white individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.

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The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic Transthyretin expression

10.1101/2021.07.14.21260525 ◽

2021 ◽

Author(s):

Gita A Pathak ◽

Antonella De Lillo ◽

Frank Wendt ◽

Flavio De Angelis ◽

Dora Koller ◽

...

Keyword(s):

Electronic Health Records ◽

Health Outcomes ◽

Bone Fracture ◽

Neuronal Response ◽

Genetic Regulation ◽

Uk Biobank ◽

Health Records ◽

Hepatic Expression ◽

Electronic Health ◽

The Uk

Background: Transthyretin (TTR) is a multi-function protein involved in the systemic transport of retinol and thyroxine. It also participates in the neuronal response to stress and proteolysis of few specific substrates. TTR is also the precursor of the fibrils that compromise organ function in the familial and sporadic systemic amyloidoses (ATTR). RNA-interference and anti-sense therapeutics targeting TTR hepatic transcription have been shown to reduce TTR amyloid formation. The goal of our study was to investigate the role of genetic regulation of TTR transcriptomic variation in human traits and diseases. Methods and Findings: We leveraged genetic and phenotypic information from the UK Biobank and transcriptomic profiles from the GTEx (Genotype-Tissue Expression) project to test the association of genetically regulated TTR gene expression with 7,149 traits assessed in 420,531 individuals. We conducted a joint multi-tissue analysis of TTR transcription regulation and identified an association with a specific operational procedure related to secondary open reduction of fracture of bone (p=5.46x10-6, false discovery rate q=0.039). Using tissue-specific TTR cis expression quantitative trait loci, we demonstrated that the association is driven by the genetic regulation of TTR hepatic expression (odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.85-6.44, p = 9.51x10-5). Although there is an established relationship of retinol and thyroxine abnormalities with bone loss and the risk of bone fracture, this is the first evidence of a possible effect of TTR transcriptomic regulation. Investigating the UK Biobank electronic health records available, we investigated the comorbidities affecting individuals undergoing the specific surgical procedure. Excluding medical codes related to bone fracture events, we identified a pattern of health outcomes that have been previously associated with ATTR manifestations. These included osteoarthritis (OR=3.18, 95%CI=1.93-4.25, p=9.18x10-8), carpal tunnel syndrome (OR=2.15, 95%CI=1.33-3.48, p=0.002), and a history of gastrointestinal diseases (OR=2.01, 95%CI=1.33-3.01, p=8.07x10-4). Conclusions: The present study supports the notion that TTR hepatic expression can affect health outcomes linked to physiological and pathological processes presumably related to the encoded protein. Our findings highlight how the integration of omics information and electronic health records can successfully dissect the complexity of multi-function proteins such as TTR.

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Modification of Heritability for Educational Attainment and Fluid Intelligence by Socioeconomic Deprivation in the UK Biobank

American Journal of Psychiatry ◽

10.1176/appi.ajp.2020.20040462 ◽

2021 ◽

pp. appi.ajp.2020.2

Author(s):

Mathias Rask-Andersen ◽

Torgny Karlsson ◽

Weronica E. Ek ◽

Åsa Johansson

Keyword(s):

Educational Attainment ◽

Fluid Intelligence ◽

Socioeconomic Deprivation ◽

Uk Biobank ◽

The Uk

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Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study

Scientific Reports ◽

10.1038/srep11208 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 192

Author(s):

Felix R Day ◽

Cathy E Elks ◽

Anna Murray ◽

Ken K Ong ◽

John R.B. Perry

Keyword(s):

Cardiovascular Disease ◽

Health Outcomes ◽

Uk Biobank ◽

Men And Women ◽

The Uk

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Frequent Daytime Napping is Detrimental to Human Health: A phenotype-wide Mendelian Randomization Study

10.1101/2020.01.20.20017723 ◽

2020 ◽

Author(s):

Lanlan Chen ◽

Aowen Tian ◽

Zhipeng Liu ◽

Miaoran Zhang ◽

Xingchen Pan ◽

...

Keyword(s):

Health Outcomes ◽

Human Health ◽

Mendelian Randomization ◽

Wide Spectrum ◽

Association Studies ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Major Depressive ◽

Genome Wide ◽

The Uk

ABSTRACTBackgroundIt remains controversial whether daytime napping is beneficial for human health.ObjectiveTo examine the causal relationship between daytime napping and the risk for various human diseases.DesignPhenotype-wide Mendelian randomization study.SettingNon-UK Biobank cohorts reported in published genome-wide association studies (GWAS) provided the outcome phenotypes in the discovery stage. The UK Biobank cohort provided the outcome phenotypes in the validation stage.ParticipantsThe UK Biobank GWAS included 361,194 European-ancestry residents in the UK. Non-UKBB GWAS included various numbers of participants.ExposureSelf-reported daytime napping frequency.Main outcome measureA wide-spectrum of human health outcomes including obesity, major depressive disorder, and high cholesterol.MethodsWe examined the causal relationship between daytime napping frequency in the UK Biobank as exposure and a panel of 1,146 health outcomes reported in genome-wide association studies (GWAS), using a two-sample Mendelian randomization analysis. The significant findings were further validated in the UK Biobank health outcomes of 4,203 human traits and diseases. The causal effects were estimated using a fixed-effect inverse variance weighted model. MR-Egger intercept test was applied to detect horizontal pleiotropy, along with Cochran’s Q test to assess heterogeneity among the causal effects of IVs.FindingsThere were significant causal relationships between daytime napping frequency and a wide spectrum of human health outcomes. In particular, we validated that frequent daytime napping increased the risks of major depressive disorder, obesity and abnormal lipid profile.InterpretationThe current study showed that frequent daytime napping mainly had adverse impacts on physical and mental health. Cautions should be taken for health recommendations on daytime napping. Further studies are necessary to precisely define the best daytime napping strategies.

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Epigenome-wide association analysis of daytime sleepiness in the Multi-Ethnic Study of Atherosclerosis reveals African-American specific associations

10.1101/447474 ◽

2018 ◽

Author(s):

Richard Barfield ◽

Heming Wang ◽

Yongmei Liu ◽

Jennifer A Brody ◽

Brenton Swenson ◽

...

Keyword(s):

Dna Methylation ◽

African Americans ◽

Health Outcomes ◽

Association Analysis ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Uk Biobank ◽

Ethnic Study ◽

The Uk ◽

Future Work

AbstractStudy ObjectivesExcessive daytime sleepiness (EDS) is a consequence of inadequate sleep, or of a primary disorder of sleep-wake control. Population variability in prevalence of EDS and susceptibility to EDS are likely due to genetic and biological factors as well as social and environmental influences. Epigenetic modifications (such as DNA methylation-DNAm) are potential influences on a range of health outcomes. Here, we explored the association between DNAm and daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS).MethodsWe performed multi-ethnic and ethnic-specific epigenome-wide association studies for DNAm and ESS in 619 individuals from the Multi-Ethnic Study of Atherosclerosis. Replication was assessed in the Cardiovascular Health Study (CHS). Genetic variants in genes proximal to ESS-associated DNAm were analyzed to identify methylation quantitative trait loci and followed with replication of genotype-sleepiness associations in the UK Biobank.Results61 methylation sites were associated with ESS (FDR ≤ 0.1) in African Americans only, including an association inKCTD5, a gene strongly implicated in sleep. One association (cg26130090) replicated in CHS African Americans (p-value 0.0004). We identified a sleepiness-associated methylation site in the geneRAI1, a gene associated with sleep and circadian phenotypes. In a follow-up analysis, a genetic variant withinRAI1associated with both DNAm and sleepiness score. The variant’s association with sleepiness was replicated in the UK Biobank.ConclusionsOur analysis identified methylation sites in multiple genes that may be implicated in EDS. These sleepiness-methylation associations were specific to African Americans. Future work is needed to identify mechanisms driving ancestry-specific methylation effects.Statement of SignificanceExcessive daytime sleepiness is associated with negative health outcomes such as reduction in quality of life, increased workplace accidents, and cardiovascular mortality. There are race/ethnic disparities in excessive daytime sleepiness, however, the environmental and biological mechanisms for these differences are not yet understood. We performed an association analysis of DNA methylation, measured in monocytes, and daytime sleepiness within a racially diverse study population. We detected numerous DNA methylation markers associated with daytime sleepiness in African Americans, but not in European and Hispanic Americans. Future work is required to elucidate the pathways between DNA methylation, sleepiness, and related behavioral/environmental exposures.

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Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour

10.1101/299826 ◽

2018 ◽

Cited By ~ 1

Author(s):

Eleanor Sanderson ◽

George Davey Smith ◽

Jack Bowden ◽

Marcus R. Munafò

Keyword(s):

Educational Attainment ◽

Health Outcomes ◽

Cognitive Ability ◽

Smoking Behaviour ◽

Mendelian Randomisation ◽

Individual Data ◽

General Cognitive Ability ◽

Uk Biobank ◽

The Uk ◽

Summary Data

AbstractRecent analyses have shown educational attainment to be associated with a number of health outcomes. This association may, in part, be due to an effect of educational attainment on smoking behaviour. In this study we apply a multivariable Mendelian randomisation design to determine whether the effect of educational attainment on smoking behaviour could be due to educational attainment or general cognitive ability. We use individual data from the UK Biobank study (N = 120,050) and summary data from large GWAS studies of educational attainment, cognitive ability and smoking behaviour. Our results show that more years of education are associated with a reduced likelihood of smoking which is not due to an effect of general cognitive ability on smoking behaviour. Given the considerable physical harms associated with smoking, the effect of educational attainment on smoking is likely to contribute to the health inequalities associated with differences in educational attainment.

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