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Background: Diet habit is associated with mental health which has been suggested to be an independent risk factor. Nevertheless, evidence concerning the association between beverage consumption and age-specific mental health remains limited. Here we estimate the association between six types of beverages and depression and anxiety disorders., Methods: We included 188,355 participants who completed at least one dietary questionnaire and were free of depression and anxiety disorders at baseline from the UK-Biobank. Cox proportional hazard models and substituting analyses were used., Results: (i) During an average of 11.15 years of follow-up, 5884(3.12 %) participants with incident depression and 6445(3.42 %) anxiety disorders were documented. (ii)In individuals aged <60 years, the consumption of SSBs (sugar-sweetened beverages) and ASBs (artificially-sweetened beverages) (>1 serving/day) was associated with higher hazard of depression disorders (SSBs: HR 1.14, 95 % CI 1.02-1.28; ASBs: HR 1.23, 95 % CI 1.09-1.38); whereas, intakes of pure fruit/vegetable juices (PiSs) and coffee were associated with lower hazard of depression disorders(PiSs: HR 0.81, 95 % CI 0.72-0.92; coffee: HR 0.88, 95 % CI 0.81-0.96). (iii)In individuals aged ≥60 years, higher intakes of PiSs and coffee were related to lower hazard of depression and anxiety disorders. (iv)Replacing PiSs or coffee with SSBs was significantly associated with reduced depression and anxiety disorders in individuals aged <60 years while replacing PiSs or coffee with milk was consistently correlated with lower depression and anxiety disorders in those aged over 60 years., Conclusion: Individual beverages showed divergent associations with depression and anxiety disorders at different age levels, which underscores the potential relationship of prudent beverage choices in mitigating the risk of mental health., Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background : Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, with dietary interventions showing promise in reducing CVD risk factors. Phytosterols (PSs) in plant-based foods may reduce CVD risk by lowering low-density lipoprotein cholesterol. However, the relationship between dietary PS intake and CVD outcomes remains inconclusive. Methods : This study investigated the association between dietary PS intake and CVD outcomes, including coronary heart disease (CHD) and cardiovascular mortality, using a large cohort of 167 209 UK Biobank participants. PS intake was assessed through repeated 24 hour dietary recall data, with participants stratified into quintiles. The Cox proportional-hazards model was used to estimate hazard ratios (HRs) for CVD risk across quintiles of PS intake, adjusting for potential confounders. Restricted cubic splines were used to examine the nonlinear relationship between phytosterol intake and cardiovascular disease risk. Sensitivity and subgroup analyses explored interactions with demographic and lifestyle factors. Results : Higher dietary PS intake was significantly associated with a reduced risk of CVD events, including CHD and cardiovascular mortality. Each 100 mg increase in PS intake was linked to an 8% reduction in CVD risk (HR = 0.92, 95% CI: 0.87, 0.97). Multivariable-adjusted analyses revealed that participants in the highest quintile of PS intake had significantly lower CVD hazard ratios (HR = 0.81, 95% CI: 0.77, 0.84) compared to those in the lowest quintile. Significant inverse associations were also observed for cardiovascular mortality (HR: 0.86, 95% CI: 0.80, 0.94) and CHD (HR: 0.91, 95% CI: 0.84, 0.98). Subgroup analysis highlighted stronger inverse associations in current smokers, individuals with lower body mass index (BMI), and those with moderate to high physical activity levels, with variations observed based on dyslipidemia status. Sensitivity analyses, excluding early events and adjusting for energy intake, confirmed the robustness of the findings. Conclusions : This large cohort study provides evidence supporting the cardioprotective effects of dietary PS intake, particularly for CHD and cardiovascular mortality. Dietary PS may be considered an integral component of heart-healthy diets.

Background: Post-COVID-19 condition (PCC) affects millions of people, and is an essential component of the long-term impact of COVID-19 during the post-pandemic era. Yet, consensus on clinical case definition and core components of PCC remains lacking, affecting our ability to inform research and evidence-based management. Our study aims 1) to identify the most specific symptoms for PCC, and identify clinical subtypes; 2) to evaluate both virus- and host-related determinants of PCC, and 3) assess the impact of PCC on physical and mental health., Methods: We studied participants from UK Biobank who completed a health and wellbeing survey between June and September 2022. Participants reported the current conditions of the presence, duration, and functional limitations of 45 symptoms, using an online questionnaire designed specifically for COVID-19 research. SARS-CoV-2 infection status and disease history were obtained through linkage to surveillance data and electronic medical records, respectively. Participants reporting symptoms within 30 days after infection (acute phase) were excluded. The most specific PCC symptoms were defined using two criteria: statistical significance (P < 0.05 after Bonferroni correction) and clinical relevance (absolute risk increase > 5%). Propensity score weighting was used to control for confounding. Subtypes of PCC were then defined based on the specific symptoms among the COVID-19 infected individuals. A multivariable regression was used to study pathogen- and host-related risk factors for PCC, and its impact on 13 physical and 4 mental health patient-reported functional outcomes., Findings: 172,303 participants (mean age 68.9, 57.4% female) were included in the analysis, of whom 43,395 had PCR-confirmed COVID-19. We identified 10 most specific symptoms and classified four PCC subtypes: ENT subtype (30.1%), characterized by alterations in smell, taste, and hearing loss; cardiopulmonary subtype (10.4%), characterized by shortness of breath, postural tachycardia, chest tightness, and chest pressure; neurological subtype (23.5%), characterized by brain fog and difficulty speaking; and general fatigue subtype (38.0%), characterized by mild fatigue. A higher PCC risk was observed for patients with Wild-type variant, multiple infections, and severe acute COVID-19 illness, consistently across the four PCC subtypes. In addition, a range of factors, including socioeconomic deprivation, higher BMI, unhealthy lifestyle, and multiple chronic health conditions, were associated with increased PCC risk, except for age and sex. Conversely, vaccination was associated with a largely reduced PCC risk, particularly for the cardiopulmonary subtypes. Individuals with PCC experienced a much worse physical and mental health. Specifically, the cardiopulmonary subtype had the most pronounced adverse impact on function impairments, followed by neurological, mild fatigue, and ENT subtype. The most affected functions included the ability to concentrate, participate in day-to-day work, and emotional vulnerability to health problems., Interpretation: PCC can be categorized into four distinct subtypes based on ten core symptoms. These subtypes appeared to share a majority of pathogen and host-related risk factors, but their impact on health varied markedly by subtype. Our findings could help refine current guidelines for precise PCC diagnosis and progression, enhance the identification of PCC subgroups for targeted research, and inform evidence-based policy making to tackle this new and debilitating condition., Funding: NIHR Senior Research Fellowship (grant SRF-2018-11-ST2-004)., Competing Interests: Declaration of interests D.P.-A. reported grants from Amgen, UCB Biopharma, Les Laboratoires Servier, Novartis, and Chiesi-Taylor, as well as speaker fees and advisory board membership with AstraZeneca and Johnson and Johnson outside the submitted work, in addition to research support from Janssen. R.P. has participated in advisory boards for Gilead, MSD, ViiV Healthcare, Theratechnologies and Lilly. His institution has received research support from Gilead, MSD, and ViiV Healthcare. The remaining authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding the genetic basis of COVID-19 vaccine seroconversion is crucial to study the role of genetics on vaccine effectiveness. In our study, we used UK Biobank data to find the genetic determinants of COVID-19 vaccine-induced seropositivity and breakthrough infections. We conducted four genome-wide association studies among vaccinated participants for COVID-19 vaccine seroconversion and breakthrough susceptibility and severity. Our findings confirmed a link between the HLA region and seroconversion after the first and second doses. Additionally, we identified 10 genomic regions associated with breakthrough infection (SLC6A20, ST6GAL1, MUC16, FUT6, MXI1, MUC4, HMGN2P18-KRTCAP2, NFKBIZ and APOC1), and one with breakthrough severity (APOE). No significant evidence of genetic colocalisation was found between those traits. Our study highlights the roles of individual genetic make-up in the varied antibody responses to COVID-19 vaccines and provides insights into the potential mechanisms behind breakthrough infections occurred even after the vaccination., (© 2024. The Author(s).)

Background: Unraveling gene-environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population., Objective: We investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence., Methods: This study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution ( PM 2.5 , PM 10 , NO 2 , and NO x ) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales., Results: Among 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for PM 2.5 , 1.20 (95% CI: 1.19, 1.22) for PM 10 , 1.13 (95% CI: 1.12, 1.15) for NO 2 , and 1.12 (95% CI: 1.11, 1.13) for NO x . In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants ( ∼ 255 % to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI., Discussion: There were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291.

Objective: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS., Methods: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms., Results: In this study, a total of 539 cases of ALS were recorded after a median follow-up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19-1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19-1.95; HR: 1.31, 95% CI: 1.06-1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ-glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega-6 fatty acids to omega-3 fatty acids ratio., Interpretation: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024;96:788-801., (© 2024 American Neurological Association.)

Objectives: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients., Design: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes., Setting and Participants: Dementia-free UK Biobank participants with chronic pain and regular analgesic use., Measurements: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively., Results: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ 2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ 2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ 2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ 2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes., Conclusion: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness., (© 2024. The Author(s).)

Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection (n = 26,101), contemporary control with no evidence of infection (n = 380,337) and historical control predating the pandemic (n = 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42-1.67; P = 1.70 × 10 -24 ; difference in incidence rate: 27.36, 95% CI 21.16-34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70-2.78; P = 5.80 × 10 -10 ) than those not hospitalized (1.41, 1.30-1.53; P = 1.46 × 10 -16 ), and were reduced in fully vaccinated people (0.97, 0.80-1.19; P = 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49-1.79; P = 4.95 × 10 -26 ). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78-1.07; P = 0.278) but increased prescription risk (1.42, 1.00-2.02; P = 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders., (© 2024. The Author(s).)

Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HR Q4vsQ1 : 0.48 (95% CI: 0.33-0.69) and 0.48 (95% CI: 0.28-0.81), respectively] and CLD mortality [HR Q4vsQ1 : 0.21 (95% CI: 0.13-0.33) and 0.15 (95% CI: 0.08-0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HR Q4vsQ1 : 3.55 (95% CI: 2.25-5.61) for HCC and 6.34 (95% CI: 3.68-10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes., (© 2024. The Author(s).)

Evidences on the association between exposure to air pollution and liver enzymes was scarce in low pollution area. We aimed to investigate the association between air pollution and liver enzyme levels and further explore whether alcohol intake influence this association. This cross-sectional study included 425,773 participants aged 37 to 73 years from the UK Biobank. Land Use Regression was applied to assess levels of PM 2.5 , PM 10 , NO 2 , and NOx. Levels of liver enzymes including AST, ALT, GGT, and ALP were determined by enzymatic rate method. Long-term low-level exposure to PM 2.5 (per 5-μg/m 3 increase) was significantly associated with AST (0.596% increase, 95% CI, 0.414 to 0.778%), ALT (0.311% increase, 0.031 to 0.593%), and GGT (1.552% increase, 1.172 to 1.933%); The results were similar for PM 10 ; NO X and NO 2 were only significantly correlated with AST and GGT Significant modification effects by alcohol consumption were found (P-interaction < 0.05). The effects of pollutants on AST, ALT, and GGT levels gradually increased along with the weekly alcohol drinking frequency. In conclusion, long-term low-level air pollutants exposure was associated with elevated liver enzyme levels. And alcohol intake may exacerbate the effect of air pollution on liver enzymes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: This study aimed to investigate the association between night shift work and the risk of nonalcoholic fatty liver disease (NAFLD)., Methods: We conducted a prospective analysis of 281,280 UK Biobank participants. Cox proportional hazards models were used to estimate the association of night shift work with incident NAFLD. Polygenic risk score analyses were performed to assess whether a genetic predisposition to NAFLD modified the association., Results: During a median follow-up of 12.1 years (3,373,964 person-years), 2,555 incident NAFLD cases were identified. Compared with workers who never/rarely worked night shifts, those who worked some night shifts or usual/permanent night shifts were 1.12 (95% CI: 0.96-1.31) and 1.27 (95% CI: 1.08-1.48) times more likely to develop NAFLD, respectively. Among the 75,059 participants who had reports on lifetime experience of night shift work, those with a longer duration, a higher frequency, more consecutive night shifts and a longer length per shift all showed higher risks of incident NAFLD. Further analyses showed that the association between night shift work and incident NAFLD was not modified by a genetic predisposition to NAFLD., Conclusions: Night shift work was associated with increased risks of incident NAFLD., (© 2023. The Author(s).)

Background: Short-term exposure to air pollution has been linked to pneumonia risk. However, evidence on the long-term effects of air pollution on pneumonia morbidity is scarce and inconsistent. We investigated the associations of long-term air pollutant exposure with pneumonia and explored the potential interactions with smoking., Research Question: Is long-term exposure to ambient air pollution associated with the risk of pneumonia, and does smoking modify the associations?, Study Design and Methods: We analyzed data in 445,473 participants without pneumonia within 1 year before baseline from the UK Biobank. Annual average concentrations of particulate matter (particulate matter with a diameter < 2.5 μm [PM 2.5 ] and particulate matter with a diameter < 10 μm [PM 10 ]), nitrogen dioxide (NO 2 ), and nitrogen oxides (NO x ) were estimated using land-use regression models. Cox proportional hazards models were used to assess the associations between air pollutants and pneumonia incidence. Potential interactions between air pollution and smoking were examined on both additive and multiplicative scales., Results: The hazard ratios of pneumonia for each interquartile range increase in PM 2.5 , PM 10 , NO 2 , and NO x concentrations were 1.06 (95% CI, 1.04-1.08), 1.10 (95% CI, 1.08-1.12), 1.12 (95% CI, 1.10-1.15), and 1.06 (95% CI, 1.04-1.07), respectively. There were significant additive and multiplicative interactions between air pollution and smoking. Compared with individuals who had never smoked with low air pollution exposure, individuals who had ever smoked with high air pollution exposure had the highest pneumonia risk (PM 2.5 : hazard ratio [HR], 1.78; 95% CI, 1.67-1.90; PM 10 : HR, 1.94; 95% CI, 1.82-2.06; NO 2 : HR, 2.06; 95% CI, 1.93-2.21; NO x : HR, 1.88; 95% CI, 1.76-2.00). The associations between air pollutants and pneumonia risk persisted in participants exposed to air pollutants concentrations meeting the European Union limits., Interpretation: Long-term exposure to air pollutants was associated with an increased risk of pneumonia, especially in individuals who smoke., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The association of serum uric acid (SUA) levels with liver-related morbidity and mortality remains undetermined. Therefore, we aimed to explore the association of SUA levels with liver-related morbidity and mortality., Methods: The present cohort study included 459 619 adults from the UK Biobank. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SUA levels with morbidity and mortality of overall liver disease. Mendelian randomization (MR) analyses were conducted to explore the underlying causality. A polygenic risk score was generated to assess whether there was a gene-exposure interaction., Results: During a median follow-up of 12.6 years, 14 302 nonfatal and 609 fatal cases of overall liver disease were identified. Compared to individuals in the lowest quartile, the HRs (95% CI) of incident overall liver disease were 1.08 (1.02-1.14), 1.13 (1.07-1.20) and 1.44 (1.36-1.53) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. Similarly, the HRs (95% CI) of liver disease-associated mortality were 1.09 (0.78-1.52), 1.55 (1.14-2.13) and 1.96 (1.42-2.69) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. The MR results did not support the causal association of SUA levels with liver disease. In addition, there was a significant modification effect of the polygenic risk score on the association of SUA levels with incident overall liver disease (p interaction  = .003)., Conclusions: Higher SUA levels were significantly associated with an increased risk of overall liver disease morbidity and mortality., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: The adverse effects of air pollutants on the risk of most cardiovascular diseases (CVDs) are well-established, but the risk of CVDs such as deep vein thrombosis, pulmonary embolism, or aortic valve stenosis have been underappreciated, especially in the diabetic population. This study aimed to evaluate associations between long-term air pollutants exposure and the risk of incident CVDs among participants with diabetes., Methods: This study included 27,827 participants with baseline diabetes from the UK Biobank. We then estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CVDs associated with chronic air pollutant exposure in the diabetic population by fitting the Cox proportional hazards model. Moreover, we investigated the cardiovascular effects of air pollutants at concentrations below WHO guideline limits., Results: After multivariable adjustment, long-term NO 2 and NO x exposures were positively associated with the development of 8 and 6 types of CVDs in participants with diabetes, respectively. In term of particulate matters, the effect estimates ranged from 1.51 (1.13, 2.03) (coronary artery disease) to 4.65 (2.73, 7.92) (peripheral arterial disease) per 10 μg/m 3 increase in PM 2.5 . Whereas, the effect estimates ranged from 1.15 (1.04, 1.27) (arterial hypertension) to 2.28 (1.40, 3.69) (pulmonary embolism) per 10 μg/m 3 increase in PM 10 . In addition, our study discovered that for most of the cardiovascular events (8 of 9), the deleterious effects of air pollutants persisted even when participants were exposed to air pollutants concentrations below WHO guideline limits., Conclusions: Long-term exposure to ambient NO 2 , NO x , PM 2.5 , and PM 10 , either at normal or low level, increased risk of various cardiovascular outcomes in the diabetic population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Evidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations., Methods: This population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM 2.5 , PM 10 , NO 2 , and NO x were estimated using a Land Use Regression model. A lifestyle score was determined based on a combination of smoking, alcohol drinking, physical activity, television viewing time, sleep duration, and diet. A polygenic risk score (PRS) was defined using 17 MDD-associated genetic loci., Results: During a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM 2.5 (HR: 1.16, 95% CI: 1.07-1.26; per 5 μg/m 3 ) and NO x (HR: 1.02, 95% CI: 1.01-1.05; per 20 μg/m 3 ) were associated with increased risk of MDD. There was a significant interaction between the genetic susceptibility and air pollution for MDD (P-interaction < 0.05). Compared with participants with low genetic risk and low air pollution, those with high genetic risk and high PM 2.5 exposure had the highest risk of incident MDD (PM 2.5 : HR: 1.34, 95% CI: 1.23-1.46). We also observed an interaction between PM 2.5 exposure and unhealthy lifestyle (P-interaction < 0.05). Participants with the least healthy lifestyle and high air pollution exposures had the highest MDD risk when compared to those with the most healthy lifestyle and low air pollution (PM 2.5 : HR: 2.22, 95% CI: 1.92-2.58; PM 10 : HR: 2.09, 95% CI: 1.78-2.45; NO 2 : HR: 2.11, 95% CI: 1.82-2.46; NO x : HR: 2.28, 95% CI: 1.97-2.64)., Conclusions: Long-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health., (© 2023. The Author(s).)

Large longitudinal studies exploring the role of dietary patterns in the assessment of long-term outcomes of NAFLD are still lacking. We conducted a prospective analysis of 128,695 UK Biobank participants. Cox proportional hazards models were used to estimate the risk associated with two dietary patterns for long-term outcomes of NAFLD. During a median follow-up of 12.5 years, 1925 cases of end-stage liver disease (ESLD) and 12,466 deaths occurred in patients with NAFLD. Compared with patients in the lowest quintile, those in the highest quintile of the diet quality score was negatively associated with the risks of ESLD and all-cause mortality (HRQ5vsQ1: 0.76, 95% CI: 0.66−0.87, p < 0.001; HRQ5vsQ1: 0.84, 95% CI: 0.79−0.88, p < 0.001, respectively). NAFLD patients with high-quality carbohydrate patterns carried a 0.74-fold risk of ESLD and a 0.86-fold risk of all-cause mortality (HRQ5vsQ1: 0.74, 95% CI: 0.65−0.86, p < 0.001; HRQ5vsQ1: 0.86, 95% CI: 0.82−0.91, p < 0.001, respectively). For prudent dietary patterns rich in vegetables, fruits and fish, the adjusted HR Q5vsQ1 (95% CI) was 0.87 (0.76−0.99) and 0.94 (0.89−0.99) for ESLD and all-cause mortality of NAFLD patients. There was a U-shaped association between the meat-rich dietary pattern and all-cause mortality in patients with NAFLD. These findings suggest that a diet characterized by a high-quality, high intake of vegetables, fruits, fish and whole grains as well as an appropriate intake of meat, was associated with a lower risk of adverse outcomes of NAFLD.

Objective: The present study aims to investigate the association between PM 2.5 exposure and major depressive disorder, and to examine whether vitamin D and physical activity could attenuate the impact of PM 2.5 on major depressive disorder., Methods: 39168 elderly adults (age≥60 years) who had valid estimates on exposure of PM 2.5 in 2010 and data on major depressive disorder were extracted from the UK Biobank. Major depressive disorder was assessed by lifetime experience of mild, moderate, and severe major depression with validated instruments. Logistic regression models were used to estimate the association between PM 2.5 exposure and major depressive disorder., Results: A total of 9079 participants had major depressive disorder, with a prevalence of 23.2%. The odds ratio (OR) of major depressive disorder was 1.096 (1.023, 1.175) for participants in the highest quartile compared with the lowest quartile of PM 2.5 . The correlation of PM 2.5 with major depressive disorder generally increased with the decreasing levels of vitamin D. For instance, in participants with the highest quartile of PM 2.5 , the corresponding ORs were 1.141 (0.951, 1.369), 1.232 (1.027, 1.478), 1.286 (1.072, 1.543), and 1.390 (1.159, 1.667) for those who had adequate, desirable, insufficient, and deficient levels of vitamin D, respectively. Additionally, significant modification effects of physical activity on the relationship between PM 2.5 and major depressive disorder were also observed., Conclusions: Our study suggests that high levels of vitamin D and physical activity may attenuate the relationship between PM 2.5 and major depressive disorder among elderly adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; P nonadjusted  = .003, P adjusted  = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers., (© 2021 UICC.)

Background: Epidemiological evidence remains conflicting regarding diet and risk of lung cancer., Objectives: We sought to systematically investigate whether dietary factors are associated with the risk of incident lung cancer in the UK Biobank., Methods: A total of 416,588 participants (54% women) from the UK Biobank were included in the present study. Based on baseline data from FFQs, 3 main dietary patterns were identified by using principal component analysis. Cox proportional hazards models were used to investigate the association of individual food groups and dietary patterns with lung cancer risk., Results: During a median follow-up of 7.13 y, 1782 incident lung cancer cases were documented. The association analysis showed high intake of red meat and processed meat was associated with an increased risk of lung cancer (HRper 50 g/d: 1.36; 95% CI: 1.13, 1.65 for red meat; HRper 25 g/d: 1.30; 95% CI: 1.10, 1.53 for processed meat). However, the consumption of fruits (HRper 100 g/d: 0.90; 95% CI: 0.84, 0.95), vegetables (HRper 100 g/d: 0.89; 95% CI: 0.81, 0.99), breakfast cereals (HRper 50 g/d: 0.81; 95% CI: 0.74, 0.89), and dietary fiber (HRper 5 g/d: 0.76; 95% CI: 0.69, 0.84) was inversely associated with the risk of lung cancer. For the dietary pattern analysis [quartile (Q) comparison], high adherence to the Prudent pattern (HRQ4 compared with Q1: 0.84; 95% CI: 0.73, 0.96) was associated with a lower risk of lung cancer, whereas the Western pattern (HRQ4 compared with Q1: 1.27; 95% CI: 1.11, 1.46) was associated with a higher risk of lung cancer., Conclusions: Our study indicated that a diet characterized by high intake of fruits, vegetables, breakfast cereals, and dietary fiber, as well as low intake of red meat and processed meat, was associated with a lower risk of lung cancer., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Rationale: Both genetic and environmental factors contribute to lung cancer, but the degree to which air pollution modifies the impact of genetic susceptibility on lung cancer remains unknown. Objectives: To investigate whether air pollution and genetic factors jointly contribute to incident lung cancer. Methods: We analyzed data from 455,974 participants (53% women) without previous cancer at baseline in the UK Biobank. The concentrations of particulate matter (PM) (PM ⩽2.5 μm in aerodynamic diameter [PM 2.5 ], coarse PM between 2.5 μm and 10 μm in aerodynamic diameter [PM coarse ], and PM ⩽10 μm in aerodynamic diameter [PM 10 ]), nitrogen dioxide (NO 2 ), and nitrogen oxides (NO x ) were estimated by using land-use regression models, and the association between air pollutants and incident lung cancer was investigated by using a Cox proportional hazard model. Furthermore, we constructed a polygenic risk score and evaluated whether air pollutants modified the effect of genetic susceptibility on the development of lung cancer. Measurements and Main Results: The results showed significant associations between the risk of lung cancer and PM 2.5 (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.33-2.01; per 5 μg/m 3 ), PM 10 (HR, 1.53; 95% CI, 1.20-1.96; per 10 μg/m 3 ), NO 2 (HR, 1.10; 95% CI, 1.05-1.15; per 10 μg/m 3 ), and NO x (HR, 1.13; 95% CI, 1.07-1.18; per 20 μg/m 3 ). There were additive interactions between air pollutants and the genetic risk. Compared with participants with low genetic risk and low air pollution exposure, those with high air pollution exposure and high genetic risk had the highest risk of lung cancer (PM 2.5 : HR, 1.71; 95% CI, 1.45-2.02; PM 10 : HR, 1.77; 95% CI, 1.50-2.10; NO 2 : HR, 1.77; 95% CI, 1.42-2.22; NO x : HR, 1.67; 95% CI, 1.43-1.95). Conclusions: Long-term exposure to air pollution may increase the risk of lung cancer, especially in those with high genetic risk.

Study Objectives: To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer., Methods: We included 469 691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable-adjusted hazard ratios (HRs) for lung cancer (2177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia, and snoring) and examined the interaction and joint effects with a lung cancer polygenic risk score., Results: A U-shaped association was observed for sleep duration and lung cancer risk, with an 18% higher risk (95% confidence interval [CI]: 1.07 to 1.30) for short sleepers and a 17% higher risk (95% CI: 1.02 to 1.34) for long sleepers compared with normal sleepers (7-8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95% CI: 1.07 to 1.46), but no association was found for insomnia or snoring. Compared with participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (<7 hours or >8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HRsleep duration: 1.83; 95% CI: 1.47 to 2.27; HRchronotype: 1.85; 95% CI: 1.34 to 2.56)., Conclusions: Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA., Methods: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%., Results: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis., Conclusion: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation., Trial Registration: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Chronic respiratory diseases have become a non-negligible cause of death globally. Although smoking and environmental exposures are primary risk factors for chronic respiratory diseases, genetic factors also play an important role in determining individual's susceptibility to diseases. Here we performed integrated gene-based and pathway analyses to systematically illuminate the heritable characteristics of chronic respiratory diseases., Methods: UK (United Kingdom) Biobank is a very large, population-based prospective study with over 500,000 participants, established to allow detailed investigations of the genetic and nongenetic determinants of the diseases. Utilizing the GWAS-summarized data downloaded from UK Biobank, we conducted gene-based analysis to obtain associations of susceptibility genes with asthma, chronic obstructive pulmonary disease(COPD) and pneumonia using FUSION and MAGMA software. Across the identified susceptibility regions, functional annotation integrating multiple functional data sources was performed to explore potential regulatory mechanisms with INQUISIT algorithm. To further detect the biological process involved in the development of chronic respiratory diseases, we undertook pathway enrichment analysis with the R package (clusterProfiler)., Results: A total of 195 susceptibility genes were identified significantly associated with chronic respiratory diseases (P bonferroni  < 0.05), and 24/195 located out of known susceptibility regions (e.g. WDPCP in 2p15). Within the identified susceptibility regions, functional annotation revealed an aggregation of credible variants in promoter-like and enhancer-like histone modification regions and such regulatory mechanisms were specific to lung tissues. Furthermore, 110 genes with INQUISIT score ≥1 may influence diseases susceptibility through exerting effects on coding sequences, proximal promoter and distal enhancer regulations. Pathway enrichment results showed that these genes were enriched in immune-related processes and nicotinic acetylcholine receptors pathways., Conclusions: This study implemented an integrated gene-based and pathway strategy to explore the underlying biological mechanisms and our findings may serve as promising targets for future clinical treatments of chronic respiratory diseases., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)