Power calculations.

Cohort: study used for eQTL data, Tissue: eQTL summary statistics obtained from this tissue, n eQTL: sample size for eQTL specific to tissue, r2 eQTL: proportion of variance in exposure variable explained by SNPs in gene expression GWAS, Outcome: trait used as outcome for MR, Outcome category: trait category, βOLS: regression coefficient for the observational association between the exposure and continuous outcome variables, βyx: unknown true causal association between exposure and continuous outcome, σ2 eQTL: variance of the exposure variable, σ2 GWAS: variance of the continuous outcome variable, n GWAS: sample size of GWAS, n cases GWAS: sample size of cases for binary outcomes, True OR: true odds ratio of the outcome variable per standard deviation of the exposure variable, K: proportion of cases in binary outcome, Power: estimated power for the exposure-outcome combination. (XLSX)</p

Details of GWAS used as outcomes.

IEUGWAS id: study ID in the IEU GWAS database, Outcome trait: name of the GWAS trait, Cohort: name of the GWAS cohort, Sex: sex of the GWAS population, Population: ethnicity of the GWAS population, Unit: measurement unit of the GWAS trait, Sample size: sample size of the GWAS cohort, Ref (see manuscript): reference for the study. Please refer to the manuscript. (XLSX)</p

SMR association of <i>PCSK9</i> and <i>USP24</i> gene-expression levels with phenotypes of interest.

The Y-axis represents the -log10 p-value of the MR association, while the direction signifies the direction of effect of gene-expression reduction, which serves as a proxy for PCSK9i. SMR multi-SNP analyses association of the available 25 tissues for PCSK9 and USP24 gene-expression in GTEx v8 for outcomes PCSK9 levels, LDL-C levels, and MDD. The blue and red lines signify p-value of 0.05 and Bonferroni-corrected threshold for 5 traits per gene of 0.005, respectively. (TIF)</p

Adverse metabolic and mental health outcomes associated with shiftwork in a population-based study of 277,168 workers in UK biobank^*

<p><b>Background:</b> Reported associations between shiftwork and health have largely been based on occupation-specific, or single sex studies that might not be generalizable to the entire working population. The objective of this study was to investigate whether shiftwork was independently associated with obesity, diabetes, poor sleep, and well-being in a large, UK general population cohort.</p> <p><b>Methods:</b> Participants of the UK Biobank study who were employed at the time of assessment were included. Exposure variables were self-reported shiftwork (any shiftwork and night shiftwork); and outcomes were objectively measured obesity, inflammation and physical activity and self-reported lifestyle, sleep and well-being variables, including mental health.</p> <p><b>Results:</b> Shiftwork was reported by 17% of the 277,168 employed participants. Shiftworkers were more likely to be male, socioeconomically deprived and smokers, and to have higher levels of physical activity. Univariately, and following adjustment for lifestyle and work-related confounders, shiftworkers were more likely to be obese, depressed, to report disturbed sleep, and to have neurotic traits.</p> <p><b>Conclusions:</b> Shiftwork was independently associated with multiple indicators of poor health and wellbeing, despite higher physical activity, and even in shiftworkers that did not work nights. Shiftwork is an emerging social factor that contributes to disease in the urban environment across the working population.Key messages</p><p>Studies have linked shiftwork to obesity and diabetes in nurses and industry workers, but little is known about the implications of shiftwork for the general workforce</p><p>In this large cross sectional study of UK workers, shiftwork was associated with obesity, depression and sleep disturbance, despite higher levels of physical activity.</p><p>Shiftwork was associated with multiple indicators of compromised health and wellbeing and were more likely to report neurotic traits and evening preference</p><p></p> <p>Studies have linked shiftwork to obesity and diabetes in nurses and industry workers, but little is known about the implications of shiftwork for the general workforce</p> <p>In this large cross sectional study of UK workers, shiftwork was associated with obesity, depression and sleep disturbance, despite higher levels of physical activity.</p> <p>Shiftwork was associated with multiple indicators of compromised health and wellbeing and were more likely to report neurotic traits and evening preference</p