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Objective: Light exposure is thought to be associated with blood pressure (BP). However, the existing evidence is inconsistent, and the underlying mechanisms remain unclear., Methods: This cohort study enrolled over 300,000 participants from the UK Biobank. Information on the time spent in outdoor light during typical summer and winter days was collected using questionnaires. Cases of hypertension and hypotension were identified using the 10th edition of the International Classification of Diseases codes. Cox proportional hazards regression models were employed to estimate the lightBP associations, and restricted cubic splines were utilized to detect potential nonlinear associations. Subgroup analyses were conducted to identify effect modifiers, and causal mediation analyses were performed to explore potential mechanisms., Results: Using summer light exposure as an illustration, after a median follow-up of 13.4 years, each additional hour of summer light exposure was found to be associated with an increased risk of hypertension (hazard ratio [HR] 1.011, 95 % confidence interval [CI] 1.0061.017, P-nonlinear=0.803) and a decreased risk of hypotension (0.988, 0.9770.998, P-nonlinear=0.109). The lightBP association was found to be stronger in females (P=0.022), those with short sleep durations (P=0.049), and those with a high genetic risk of hypertension (P<0.001). Potential mechanisms included increases in biological age (proportion mediated, 24.1 %, P<0.001), neutrophil count (5.4 %, P<0.001), body mass index (32.0 %, P<0.001), etc. CONCLUSIONS: Our study revealed a positive lightBP association. Potential mechanisms include inflammation, aging, and lifestyle changes. Further epidemiological and experimental investigations are necessary to validate these findings., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The count of locations with chronic pain is widely used in research and clinical practice. However, this approach might be too simplistic to fully capture the complexity of chronic pain experiences. This study identified prevalent patterns of chronic pain locations and evaluated their associations with incident dementia among middle-aged and older adults in the UK. Data were from 445,530 participants who were free of dementia at baseline (2006-2010) in the UK Biobank. We calculated the incidence rates of all-cause dementia by the 20 most prevalent combinations of pain locations assessed at baseline. Cox models were utilized to examine the hazard ratio of incident dementia among each of these 20 combinations compared to 3 groups: 1) participants without chronic pain, 2) participants with only a single chronic pain location not included in the combination, and 3) participants with only a single chronic pain location included in the combination. The 3 most prevalent combinations were neck and back (5.7%), back and knee (5.4%), and neck and knee (4.5%). Chronic back, neck, and knee pain was commonly present either individually or simultaneously in combinations associated with higher dementia rates than persons without chronic pain. The combinations involving back, neck, and knee were associated with higher dementia rates than groups with 1 pain location not included in the combination. Chronic pain is not randomly present in body locations. Understanding how different patterns of chronic pain locations relate to dementia provides new insights into dementia prevention through pain relief. PERSPECTIVE: This article unveils chronic pain patterns and dementia risks in the UK Biobank. Chronic pain in back, neck, and knee presents frequently, either individually or in combinations associated with increased dementia rates. Chronic pain combos correlate with diverse dementia rates, guiding targeted prevention strategies through pain management., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

The relationship between depression and severe non-alcoholic fatty liver disease (NAFLD) has not been clearly defined. We conducted a longitudinal cohort study and a two-sample Mendelian randomization (MR) analysis to assess the association of depression with severe NAFLD risk. We used individual data from the UK Biobank study with 481,181 participants, and summary data from published genome-wide association studies. The association between depression and severe NAFLD was assessed using Cox proportional hazards regression analysis. Two-sample MR for depression with NAFLD was conducted, the principal analysis employed the inverse variance weighted (IVW) approach. In the observational study, after a median follow-up of 13.46 years, 4,563 participants had severe NAFLD. In multivariable-adjusted model, participants with depression had an increased risk of severe NAFLD (hazards ratio:1.21, 95% confidence interval (CI):1.09-1.34), as compared to those without depression. In subgroup analyses, the association between depression and severe NAFLD risk was generally observed across different subgroups. For the MR, result also showed that genetically predicted depression was causally associated with a higher risk of NAFLD (odds ratio:1.55, 95%CI:1.10-2.19) in IVW. Our study revealed a prospective association of depression with severe NAFLD, thus potentially necessitating clinical monitoring of individuals with depression for severe NAFLD., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval The UK Biobank study has approval from the North West Multi-centre Research Ethics Committee, all methods were performed in accordance with the relevant guidelines and regulations, and all participants provided written informed consent. As our MR study was based on publicly available data, no additional ethical approval or consent was required., (© 2024. The Author(s).)

Background: Some pathogenic mechanisms suggest a potential relationship between gastroesophageal reflux disease (GERD) and respiratory diseases. However, evidence regarding the association between GERD and lung cancer is mixed. We aim to explore this relationship based on data from the large-scale UK Biobank study., Materials and Methods: We performed a cross-sectional and prospective cohort study in 501,569 (45.58% male) individuals included in the UK Biobank at baseline (2006-2010). The Cox proportional hazards model and logistic regression models were used to assess the relationship between GERD and lung cancer, small cell lung cancer (SCLC), lung squamous cell carcinoma (LUSC), and lung adenocarcinoma (LUAD)., Results: During a mean follow-up of 11.54 years, 3,863 (0.84%) incident lung cancer cases were identified. In the cross-sectional analysis using logistic models, significant associations were found between GERD and prevalent lung cancer cases (odds ratio [OR] = 1.87, 95% confidence interval [95% CI]: 1.45-2.38) and subtypes of lung cancer, with an OR (95% CI) of 3.19 (1.47-6.79) for SCLC, 2.08 (1.33-3.21) for LUSC, 1.85 (1.15-2.91) for LUAD. In the follow-up analysis using Cox models, GERD was associated with an increased risk of lung cancer (hazard ratio [HR] = 1.24, 95%CI: 1.14-1.34). Similar associations were also observed between GERD and SCLC (HR = 1.39, 95% CI: 1.09-1.78), LUSC (HR = 1.40, 95% CI: 1.18-1.65), and LUAD (HR = 1.17, 95% CI: 1.02-1.33). The risk of lung cancer resulting from GERD was mainly elevated in former smokers (HR = 1.38, 95% CI: 1.23-1.54) and current smokers (HR = 1.18, 95% CI: 1.04-1.34), but not in never-smokers (HR = 0.89, 95% CI: 0.70-1.14). No significant association was observed in former smokers who had quit smoking for at least 25 years., Conclusions: We found that GERD was positively associated with an increased risk of lung cancer, especially among smokers. Awareness of this association may be beneficial for prevention and treatment strategies of both diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Neurodegenerative diseases (NDDs) result from a complex interplay of genetic, environmental and aging factors. A balanced diet and adequate physical activity (PA) are recognized as pivotal components among modifiable environmental factors. The independent impact on NDD incidence has been previously debated. This investigation seeks to delineate the association between PA and NDDs across various levels of adherence to a plant-based diet., Methods: In this study, a cohort of 368,934 participants from the UK Biobank was analyzed. Total physical activity (TPA) levels and healthful plant-based diet index (hPDI) were calculated and categorized. A multiple adjusted Cox model was utilized to evaluate the influence of TPA and hPDI on common NDDs, respectively., Results: Finally, 4602 identified cases diagnosed as Alzheimer's disease (AD), Parkinson's disease (PD) or amyotrophic lateral sclerosis (ALS). We found that higher TPA was significantly associated with a reduced risk of developing AD (Q3: HR 0.87; Q4: HR 0.78) and PD (Q3: HR 0.86; Q4: HR 0.81). The protective effect was further accentuated with adherence to a plant-based diet. However, these connections were not observed in the analysis of ALS regardless of dietary patterns., Conclusion: Our findings underscore a significant association between higher TPA and reduced risks of AD and PD, with an enhanced effect observed in conjunction with a plant-based diet. This study contributes to addressing the knowledge gap regarding the combined impact of TPA and a plant-based diet on NDDs occurrence, providing insights into potential underlying mechanisms., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To investigate the relationship between cardiorespiratory fitness (CRF) and liver fat content (LFC) in community-based participants and highlight their relationship in people with different body mass indices (BMIs)., Materials and Methods: Using UK Biobank data, CRF was estimated with bicycle ergometer fitness testing and was evaluated based on physical work capacity at 75% maximum heart rate (PWC 75% ). LFC was quantified through liver proton density fat fraction (PDFF) on magnetic resonance imaging. Multivariate linear regression models were used to analyse the associations of CRF and BMI with absolute reduction and percentage change in PDFF (%)., Results: In total, 5765 participants with a mean age of 55.57 years and a median (range) follow-up of 10.7 (4.0-17.7) years were included. Compared with the lowest PWC 75% tertile, the absolute reduction and percentage change in PDFF in the highest PWC 75% tertile were -0.450 (95% confidence interval [CI] -0.699 to -0.192) and -4.152 (95% CI -6.044 to -2.104), respectively. These associations were independent of BMI, and individuals with obesity and normal weight had the largest absolute reduction and percentage change in LFC, respectively (p for interaction <0.001). Joint analysis showed that PWC 75% and BMI had a negative dose-response relationship with PDFF. These associations were consistent in different sex and age subgroups (p for interaction >0.05)., Conclusions: There was a significant negative association between CRF and LFC, and this association was independent of BMI. The results of this study strongly recommend improving CRF to mitigate LFC., (© 2024 John Wiley & Sons Ltd.)

This study tested whether sexual orientation differences in depressive symptoms were partially explained by the chain mediation effect of neuroticism and victimization. Using the Avon Longitudinal Study of Parents and Children from the UK (N = 4647, 36.52% men, 88% White), self-reported neuroticism, sexual orientation, and depressive symptoms were measured at age 13.5, 21, and 22 years, respectively. Childhood abuse between birth and age 11 years and the individuals' experiences of being bullied at age 17.5 years were measured as the components of victimization. Structural equation modeling was used to analyze the data. Non-heterosexual individuals reported higher depressive symptoms than heterosexual individuals, with a total effect (standardized path coefficient) of 0.590 and 0.768 for men and women, respectively. This association was partially explained by childhood abuse (indirect effect = 0.043 and 0.046 for men and women, respectively) and neuroticism directly (indirect effect = 0.036 and 0.056 for men and women, respectively). Sexual orientation differences in depressive symptoms were also partially explained by a path through increased risk of experiencing childhood abuse leading to higher levels of neuroticism (indirect effect = 0.004 and 0.009 for men and women, respectively) and by a path through higher levels of neuroticism leading to increased risk of being bullied (indirect effect = 0.004 and 0.002 for men and women, respectively). The findings suggest that while some of the association between sexual orientation and depression might be explained by neuroticism and experiences of victimization measured prospectively, these factors do not account for most of this relationship., Competing Interests: Declarations. Conflict of interest: The authors report there are no competing interests to declare. Ethics Approval: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Additional ethical approval was not required since only secondary data analyses were involved. Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. Informed Consent: Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cardiometabolic multimorbidity (CMM) and aging are increasing public health concerns. This prospective study used UK Biobank cohort to investigate the relationship between biological aging and the trajectory of CMM to dementia and mortality., Methods: CMM is the coexistence of at least two cardiometabolic diseases (CMD), including stroke, ischemic heart disease, and diabetes. Biological age was calculated using the KDM-BA and PhenoAge algorithms. Accelerated aging indicated biological age advances more rapidly than chronological age., Results: The study included 415,147 individuals with an average age of 56.5 years. During the average 11-year follow-up period, CMD-free individuals with accelerated aging had a significantly greater risk of CMD (KDM-BA, HR 1.456; PhenoAge, HR 1.404), CMM (KDM-BA, HR 1.952; PhenoAge, HR 1.738), dementia (KDM-BA, HR 1.243; PhenoAge, HR 1.212), and mortality (KDM-BA, HR 1.821; PhenoAge, HR 2.047) in fully-adjusted Cox regression models ( p  < 0.05 for all). Accelerated aging had adjusted HRs of 1.489 (KDM-BA) and 1.488 (PhenoAge) for CMM, 1.434 (KDM-BA) and 1.514 (PhenoAge) for dementia, and 1.943 (KDM-BA) and 2.239 (PhenoAge) for mortality in participants with CMD at baseline ( p  < 0.05 for all). CMM significantly mediated accelerated aging's indirect effects on dementia by 13.7% (KDM-BA, HR) and 21.6% (PhenoAge); those on mortality were 4.7% (KDM-BA) and 5.2% (PhenoAge). The population attributable-risk of Life's Essential 8 score (≥80 vs. <80) were 0.79 and 0.43 for KDM-BA and PhenoAge accelerated aging, respectively., Conclusion: Biological aging involves the entire trajectory of CMM from a CMD-free state to CMD, to CMM, and ultimately to dementia and death. Life's Essential 8 may be a potential target to counter age acceleration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Jia, Li, Wan, Lei, Liao, Zhao and Li.)

Background: Multiple psychosocial factors have been associated with dementia, while the individual or joint effects of various psychosocial states on dementia remain unrevealed due to the complex interplay between those factors. Here, the authors examined the associations of psychosocial factors and patterns with subsequent risk of dementia, and if the associations could be modified by genetic susceptibility to dementia., Methods: UK Biobank dementia-free participants were followed from one year after recruitment (median date: 24 January, 2010) until 31 October, 2022. Psychosocial states were measured by 22 items related to five dimensions, including psychiatric history, recent stressful life events, current psychiatric symptoms, social contact, and individual socioeconomic state. We identified clusters of individuals with distinct psychosocial patterns using latent class analysis. Cox proportional hazards models were used to evaluate the association between psychosocial items, as well as psychosocial patterns, and risk of dementia. We further performed stratification analyses by apolipoprotein E (APOE) genotype, polygenic risk score (PRS) of dementia, and family history of dementia., Results: Of 497,787 included participants, 54.54% were female. During a median follow-up of 12.70 years, we identified 9,858 (1.98%) patients with newly diagnosed dementia. We identified seven clusters with distinct psychosocial patterns. Compared to individuals with a pattern of 'good state', individuals with other unfavorable patterns, featured by varying degrees of poor psychological state ('fair state' and 'mildly, moderately, and extremely poor psychological state'), low social contact or socioeconomic state ('living alone' and 'short education years'), were all at an increased risk of dementia (hazard ratios [HR] between 1.29 and 2.63). The observed associations showed no significant differences across individuals with varying APOE genotypes, levels of PRS, and family histories of dementia., Conclusion: Unfavorable psychosocial patterns are associated with an increased risk of dementia, independent of genetic susceptibility. The findings highlight the importance of surveillance and prevention of cognitive decline among individuals with suboptimal psychosocial state., (© 2024. The Author(s).)

Exposure to adverse life events is linked to somatic disorders. The study aims to evaluate the association between adverse events at varying life stages and the risk of chronic kidney disease (CKD), a condition affecting about 10% population worldwide. This prospective cohort study included 140,997 participants from the UK Biobank. Using survey items related to childhood maltreatment, adulthood adversity and catastrophic trauma, we performed latent class analysis to summarize five distinct patterns of exposure to adverse life events, namely "low-level exposure", "childhood exposure", "adulthood exposure", "sexual abuse" and "child-to-adulthood exposure". We used Cox proportional hazard regression to evaluate the association of patterns of exposure to adverse life events with CKD, regression-based mediation analysis to decompose the total effect, and gene-environment-wide interaction study (GEWIS) to identify interactions between genetic loci and adverse life events. During a median follow-up of 5.98 years, 2734 cases of incident CKD were identified. Compared with the "low-level exposure" pattern, "child-to-adulthood exposure" was associated with increased risk of CKD (hazard ratio 1.37, 95% CI 1.14 to 1.65). BMI, smoking and hypertension mediated 11.45%, 9.79%, and 4.50% of this total effect, respectively. Other patterns did not show significant results. GEWIS and subsequent analyses indicated that the magnitude of the association between adverse life events and CKD differed according to genetic polymorphisms, and identified potential underlying pathways (e.g., interleukin 1 receptor activity). These findings underscore the importance of incorporating an individual's psychological encounters and genetic profiles into the precision prevention of CKD., (© 2024. The Author(s).)

Background: Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases., Objective: To estimate the risk of neurodegenerative diseases among individuals with CHIP., Methods: We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP., Results: We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01-1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05-1.63) and ALS (HR 1.50, 95% CI 1.05-2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97-1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96-1.17), AD (HR 1.04, 95% CI 0.88-1.23), and PD (HR 1.02, 95% CI 0.86-1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A-mutant CHIP, ASXL1-mutant CHIP, or SRSF2-mutant CHIP., Conclusion: Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Background: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes., Methods: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators., Results: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654)., Conclusion: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, N case /N control =40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMT max -AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMT mean -AS: HR = 1.39, 95%CI = 1.09-1.78; cIMT min -AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMT max -AS: [Formula: see text]=0.23, P=9.44 × 10 -5 ; cIMT mean -AS: [Formula: see text]=0.21, P=3.00 × 10 -4 ; cIMT min -AS: [Formula: see text]=0.16, P=6.30 × 10 -3 ). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMT max -AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMT mean -AS: OR=1.09, 95%CI=0.93-1.26; cIMT min -AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMT max : beta=0.07, 95%CI = 0.01-0.13; AS-cIMT mean : beta=0.08, 95%CI = 0.01-0.15; AS-cIMT min : beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Unhealthy sleep patterns and accelerated biological age are frequently associated with multiple chronic respiratory diseases (CRDs), including COPD, asthma, and interstitial lung disease (ILD). However, few studies have explored the role of biological age in the relationship between sleep patterns and CRDs., Objectives: To explore the association between sleep patterns and CRD, and the extent to which biological age mediates the relationship between sleep patterns and CRD., Methods: This was a prospective cohort study based on UK Biobank. The sleep score was derived from five self-reported sleep traits: sleep duration, daytime sleepiness, chronotype, snoring, and insomnia. The score ranged from 0 (least healthy) to 5 (healthiest). Biological age was represented by PhenoAgeAccel., Results: Among 303,588 participants, 11,105 (3.7 %), 9,380 (3.1 %), and 1,667 (0.5 %) were diagnosed with asthma, COPD, and ILD, respectively. Each 1-point increase in the sleep score was associated with a 0.156-year reduction in PhenoAgeAccel, and 14.3 %, 12.4 %, and 6.7 % reduction in asthma, COPD, and ILD, respectively. For each 1-year increase in PhenoAgeAccel, the risk of asthma, COPD, and ILD increased by 2.8 %, 4.3 %, and 5.7 %, respectively. PhenoAgeAccel mediated the associations between the sleep score and asthma, COPD, and ILD, with a mediated proportion (95 % CI) of 2.81 % (2.35 % to 3.27 %), 4.94 % (4.23 % to 5.66 %), and 12.48 % (10.43 % to 14.53 %), respectively., Conclusion: A better sleep score was significantly associated with younger biological age and decreased risk of CRDs, with biological age playing a mediating role in the association between sleep score and CRDs., 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 © 2024 Elsevier Inc. All rights reserved.)

Background: Late-onset seborrhoeic dermatitis seriously affects patients' quality of life. Studies have shown an association between air pollution and other inflammatory skin diseases. However, associations between air pollution exposures and the incidence of late-onset seborrhoeic dermatitis have not been elucidated., Objectives: To investigate air pollution's role in the incidence of late-onset seborrhoeic dermatitis., Methods: We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data spanning various years for specific air pollutants, namely particulate matter [PM; with an aerodynamic diameter of ≤ 2.5 µm (PM2.5), between 2.5 and 10 μm (PM2.5-10), ≤ 10 μm (PM10)] along with nitrogen oxides (NO plus NO2, denoted NOx) and NO2, were incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between air pollution and seborrhoeic dermatitis was delineated., Results: Our examination of 193 995 participants identified 3363 cases of seborrhoeic dermatitis. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated risk of seborrhoeic dermatitis. Notably, PM2.5, PM10, NO2 and NOx exhibited hazard ratios of 1.11, 1.15, 1.22 and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and onset of seborrhoeic dermatitis. Intriguingly, this association was accentuated in certain demographics, including younger men, socioeconomically deprived people, smokers, daily alcohol consumers, and those engaging in regular physical activity., Conclusions: Our findings revealed that air pollution exposures were associated with incidence of late-onset seborrhoeic dermatitis. These results emphasize the importance of preventing environmental air pollution exposures to mitigate the risk of developing the condition., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Unicompartmental knee arthroplasty (UKA) has a long history and has many advantages in some aspects over total knee arthroplasty (TKA) for patients with suitable indications, but it has not been established as a treatment at the same level with TKA. Therefore, 80 members of the British Association for Surgery of the Knee (BASK) and the European Knee Society (EKS) were invited to attend a joint meeting with the aim of creating an evidence-based consensus statement on UKA, in London, UK (December 2019). A formal consensus process was undertaken at the meeting incorporating a multiple round Delphi exercise, with group discussion of areas of agreement and disagreement between rounds. Five consensus statements were issued: ① UKA should be offered as a successful alternative to TKA in patients undergoing arthroplasty who meet agreed indications. ② When consenting a patient for UKA, information including the benefits and risks that are specific to UKA, should be tailored to and discussed with the individual patient. ③ Evidence suggests that surgeons should avoid low-volume use of UKA to optimise outcomes for their patients. ④ Surgeons should use the contemporary evidence-based indications and contraindications for medial UKA. ⑤ Knee arthroplasty surgeons should have exposure to and training in UKA. On the basis of full study of the consensus, combined with the Expert Consensus on Perioperative Management of Unicompartmental Knee Arthroplasty in China in 2020, this paper elaborates the meaning of the final evidence-based consensus for clinicians' reference.

Background: Although healthy sleep patterns have been linked to a lower risk of cardiovascular disease in earlier research, it is unclear how beneficial they are for venous thromboembolism (VTE)., Aim: This research aimed to examine the correlation between sleep patterns, genetic susceptibility, and VTE., Methods: In the UK Biobank cohort, healthy sleep behaviors were defined as early chronotype, 7-8 hours of sleep each day, no snoring, infrequent insomnia, and infrequent daytime sleepiness. Each of the five criteria was given 1 point, creating a healthy sleep score ranging from 0 to 5. Cox proportional hazards regression models were utilized to examine the associations between genetic susceptibility, healthy sleep score and VTE., Results: The UK Biobank study included 384,758 participants aged 56.6 ± 8.0 years. After a median of 11.9 years of follow-up, 8,885 (2.3%) participants were diagnosed with VTE. A healthy sleep score inversely affected VTE risk. For participants with a score of 5, the hazard ratio of VTE was 0.813 (95% confidence interval: 0.758-0.873, P<0.001) compared to those with a score ≤2. Early chronotype, sleeping 7-8 hours each day, infrequent insomnia, and infrequent daytime sleepiness were significantly associated with a 7.9%, 8.3%, 5.1%, and 20.7% lower risk of VTE, respectively. In addition, the correlation between sleep pattern and the incidence of VTE was consistent, regardless of genetic susceptibility (P for interaction = 0.366)., Conclusions: Our secondary analysis of a large-scale prospectively gathered registry revealed that individuals with a healthy sleep pattern are significantly correlated with lower risk of developing VTE, irrespective of genetic susceptibility., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking., Methods: Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models., Results: We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the "Absence of trauma and psychopathology" cluster, the "adverse childhood experiences (ACEs) with psychopathology" cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 - 1.23] for biological and 1.52 [1.18 - 1.95] for facial aging acceleration), while no such association was observed for the "ACEs without psychopathology" cluster (1.04 [0.99 - 1.09] and 1.02 [0.84 - 1.24]., Conclusions: Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals' psychological resilience to prevent aging acceleration., (© 2024. The Author(s).)

Background and Objectives: Accumulating evidence connects diverse components of body composition (e.g., fat, muscle, and bone) to neurodegenerative disease risk, yet their interplay remains underexplored. This study examines the associations between patterns of body composition and the risk of neurodegenerative diseases, exploring the mediating role of cardiovascular diseases (CVDs)., Methods: This retrospective analysis used data from the UK Biobank, a prospective community-based cohort study. We included participants free of neurodegenerative diseases and with requisite body composition measurements at recruitment, who were followed from 5 years after recruitment until April 1, 2023, to identify incident neurodegenerative diseases. We assessed the associations between different components and major patterns of body composition (identified by principal component analysis) with the risk of neurodegenerative diseases, using multivariable Cox models. Analyses were stratified by disease susceptibility, indexed by polygenetic risk scores for Alzheimer and Parkinson diseases, APOE genotype, and family history of neurodegenerative diseases. Furthermore, we performed mediation analysis to estimate the contribution of CVDs to these associations. In addition, in a subcohort of 40,790 participants, we examined the relationship between body composition patterns and brain aging biomarkers (i.e., brain atrophy and cerebral small vessel disease)., Results: Among 412,691 participants (mean age 56.0 years, 55.1% female), 8,224 new cases of neurodegenerative diseases were identified over an average follow-up of 9.1 years. Patterns identified as "fat-to-lean mass," "muscle strength," "bone density," and "leg-dominant fat distribution" were associated with a lower rate of neurodegenerative diseases (hazard ratio [HR] = 0.74-0.94) while "central obesity" and "arm-dominant fat distribution" patterns were associated with a higher rate (HR = 1.13-1.18). Stratification analysis yielded comparable risk estimates across different susceptibility groups. Notably, 10.7%-35.3% of the observed associations were mediated by CVDs, particularly cerebrovascular diseases. The subcohort analysis of brain aging biomarkers corroborated the findings for "central obesity," "muscle strength," and "arm-dominant fat distribution" patterns., Discussion: Our analyses demonstrated robust associations of body composition patterns featured by "central obesity," "muscle strength," and "arm-dominant fat distribution" with both neurodegenerative diseases and brain aging, which were partially mediated by CVDs. These findings underscore the potential of improving body composition and early CVD management in mitigating risk of neurodegenerative diseases.

Aims: Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined., Methods and Results: Utilizing the UK Biobank cohort, we assessed biological age using the Klemera-Doubal and PhenoAge methods. BAA was quantified by residual analysis compared with chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analysis was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF [26% per standard deviation (SD) increase in KDM-BA acceleration, 95% confidence intervals (CI): 23-28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32-35%]. Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk., Conclusion: In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions., Competing Interests: Conflict of interest: none declared, (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Childhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association., Methods: We included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes., Results: The mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (p for trend  < 0.01). Compared to individuals with no history of CM, individuals exposed to any CM were more likely to be hospitalized or die due to COVID-19 (odds ratio [OR] = 1.54 [95%CI 1.31-1.81]), particularly after physical neglect (2.04 [1.57-2.62]). Largely comparable risk patterns were observed across groups of high vs. low genetic risks for severe COVID-19 outcomes (p for difference  > 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01-1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13-1.29])., Conclusions: Our results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics., (© 2024. The Author(s).)

Background: The associations between cardiovascular disease (CVD) and multiple psychiatric disorders and suicide attempt, and whether different genetic susceptibilities affect such links, have not been investigated clearly., Methods and Results: Based on the UK Biobank, we conducted a matched cohort study involving 63 923 patients who were first hospitalized with a CVD diagnosis between 1997 and 2020, and their 127 845 matched unexposed individuals. Cox models were used to examine the subsequent risk of psychiatric disorders and suicide attempt (ie, anxiety, depression, stress-related disorder, substance misuse, psychotic disorder, and suicide behaviors) following CVD. We further performed stratified analyses by polygenic risk score for each studied psychiatric condition to detect the possible effects of genetic susceptibility on the observed associations. We found an increased risk of any psychiatric disorders and suicide attempt among CVD patients, compared with matched unexposed individuals, particularly within 1 year following the CVD (fully adjusted hazard ratio [HR] within 1 year, 1.83 [95% CI, 1.58-2.12]; HR after 1 year, 1.24 [95% CI, 1.16-1.32]). By subtype, the risk elevations existed for any psychiatric disorders and suicide attempt following most categories of CVDs. Analyses stratified by polygenic risk score revealed little impact of genetic predisposition to studied psychiatric conditions on these observed links., Conclusions: Patients hospitalized for CVD were at increased subsequent risk of multiple types of psychiatric disorders and suicide attempt, especially in the first year after hospitalization, irrespective of their genetic susceptibilities to studied psychiatric conditions, and these findings underscore the necessity of developing timely psychological interventions for this vulnerable population.

Background and Aims: The relationship between alcohol consumption and age-related diseases is inconsistent. Biological age (BA) serves as both a precursor and a predictor of age-related diseases; however, longitudinal associations between alcohol consumption and BA in middle-aged and older people remain unclear. We measured whether there was a longitudinal association between drinking frequency and pure alcohol intake with BA among middle-aged and older people., Design and Setting and Participants: This study involved two prospective cohort studies, set in Southwestern China and the United Kingdom. A total of 8046 participants from the China Multi-Ethnic Cohort study (CMEC) and 5412 participants from the UK Biobank (UKB), aged 30-79 years, took part, with complete data from two waves of clinical biomarkers., Measurements: BA was calculated by the Klemera Doubal's method. Accelerated BA equalled BA minus chronological age. Drinking frequency and pure alcohol intake were obtained through self-reported questionnaires. Drinking frequency in the past year was classified as current non-drinking, occasional (monthly drinking) and regular (weekly drinking)., Findings: Compared with consistent current non-drinkers, more frequent drinkers [CMEC: β = 0.46, 95% confidence interval (CI) = 0.13-0.80; UKB: β = 0.65, 95% CI = 0.01-1.29)], less frequent drinkers (CMEC: β = 0.62, 95% CI = 0.37-0.87; UKB: β = 0.54, 95% CI = -0.01-1.09), consistent occasional drinkers (CMEC: β = 0.51, 95% CI = 0.23-0.79; UKB: β = 0.63, 95% CI = 0.13-1.13) and consistent regular drinkers (CMEC: β = 0.56, 95% CI = 0.17-0.95; UKB: β = 0.46, 95% CI = 0.00-0.91) exhibited increased accelerated BA. A non-linear relationship between pure alcohol intake and accelerated BA was observed among consistent regular drinkers., Conclusions: In middle-aged and older people, any change in drinking frequency and any amount of pure alcohol intake seem to be positively associated with acceleration of biological ageing, compared with maintaining abstinence., (© 2024 Society for the Study of Addiction.)

Background: Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts., Methods: This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels., Results: A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels., Conclusions: Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Endometriosis is a poorly understood disease that affects up to 196 million women worldwide and imposes high costs in terms of economic burden and quality of life of women. Traits of circulating lipids have been related to the onset and progression of endometriosis in previous observational studies but the results have remained contradictory., Methods: We performed univariable and multivariable Mendelian randomization (MR) analyses using instrument variables to genetically predict the associations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoprotein (apo) A-I and B from the UK Biobank with endometriosis (consisting of 8288 cases and 68 969 controls from the FinnGen consortium). The inverse-variance weighted (IVW) method was used as the primary estimate, whereas MR-Egger and weighted median were conducted as complements to the IVW model., Results: Increased levels of triglycerides were associated with higher risk of endometriosis and endometriosis of the pelvic peritoneum in the univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, triglycerides still retained a robust effect. Decreased levels of apoA-I and HDL cholesterol were associated with increased risk of endometriosis and endometriosis of the pelvic peritoneum in univariable MR analyses. After mutual adjustment, HDL cholesterol retained a robust effect whereas the association for apoA-I was attenuated., Conclusions: This is the first MR-based evidence to suggest that triglycerides and HDL cholesterol are the predominant traits that account for the aetiological relationship of lipoprotein lipids with risk of endometriosis, in particular endometriosis of the pelvic peritoneum. Further well-designed randomized controlled trials are needed to address these results., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Limited evidence demonstrated the potential relationship between dietary sugar intake and dementia. This association demands further clarification in a large-scale population., Methods: A total of 210,832 participants from the UK Biobank cohort were included in this prospective cohort study. Absolute and relative sugar intake and high-sugar dietary scores were utilized to reflect dietary sugar intake. Absolute sugar intake was identified by the Oxford WebQ in the UK Biobank. Relative sugar intake was calculated by dividing the absolute sugar intake by total diet energy. High-sugar dietary pattern was identified using the method of reduced rank regression. Cox proportional hazards regression analyses and restricted cubic splines were performed to examine the longitudinal associations between dietary sugar intake and all-cause dementia and its main subtype, Alzheimer's disease. Explorative mediation analyses were conducted to explore underlying mechanisms., Results: Increased absolute sugar intake (g/day) was significantly associated with a higher risk of all-cause dementia (HR = 1.003, [95%CI: 1.002-1.004], p < 0.001) and Alzheimer's disease (1.002, [1.001-1.004], 0.005). Relative sugar intake (%g/kJ/day) also demonstrated significant associations with all-cause dementia (1.317, [1.173-1.480], p < 0.001) and Alzheimer's disease (1.249, [1.041-1.500], 0.017), while the high-sugar dietary score was only significantly associated with a higher risk of all-cause dementia (1.090, [1.045-1.136], p < 0.001). In addition, both sugar intake and high-sugar dietary score demonstrated significant non-linear relationships with all-cause dementia and Alzheimer's disease (all p values for non-linearity < 0.05)., Conclusions: Our study provided evidence that excessive sugar intake was associated with dementia. Controlling the excess consumption of dietary sugar may be of great public health implications for preventing dementia., (© 2024. The Author(s).)

Background: The role of lifestyle factors and their relative contributions to the development and mortality of cardio-renal-metabolic multimorbidity (CRMM) remains unclear., Methods: A study was conducted with 357,554 UK Biobank participants. CRMM was defined as the coexistence of two or three cardio-renal-metabolic diseases (CRMDs), including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD). The prospective study examined the associations of individual and combined lifestyle scores (diet, alcohol consumption, smoking, physical activity, sedentary behavior, sleep duration and social connection) with longitudinal progression from healthy to first cardio-renal-metabolic disease (FCRMD), then to CRMM, and ultimately to death, using a multistate model. Subsequently, quantile G-computation was employed to assess the relative contribution of each lifestyle factor., Results: During a median follow-up of 13.62 years, lifestyle played crucial role in all transitions from healthy to FCRMD, then to CRMM, and ultimately to death. The hazard ratios (95% CIs) per score increase were 0.91 (0.90, 0.91) and 0.90 (0.89, 0.91) for healthy to FCRMD, and for FCRMD to CRMM, and 0.84 (0.83, 0.86), 0.87 (0.86, 0.89), and 0.90 (0.88, 0.93) for mortality risk from healthy, FCRMD, and CRMM, respectively. Among the seven factors, smoking status contributed to high proportions for the whole disease progression, accounting for 19.88-38.10%. High-risk diet contributed the largest proportion to the risk of transition from FCRMD to CRMM, with 22.53%. Less-frequent social connection contributed the largest proportion to the risk of transition from FCRMD to death, with 28.81%. When we further consider the disease-specific transitions, we find that lifestyle scores had slightly stronger associations with development to T2D than to CVD or CKD., Conclusions: Our study indicates that a healthy lifestyle may have a protective effect throughout the longitudinal progression of CRMM, informing more effective management and treatment. Smoking status, diet, and social connection played pivotal roles in specific disease transitions., (© 2024. The Author(s).)

Background: The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect., Methods: This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects., Results: In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (β CMEC  = 0.068, β UK-Biobank  = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (β CMEC  = 0.027, β UK-Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D., Conclusions: Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well., (© 2024. The Author(s).)

Purpose: This study aims to investigate the association between Body Mass Index (BMI) and sex hormone levels utilizing a cross-sectional study design alongside Mendelian randomization (MR) analysis., Materials and Methods: A cross-sectional study was performed based on National Health and Nutrition Examination Survey (NHANES) 2013-2016. Additionally, a two-sample MR analysis was performed, utilizing Single Nucleotide Polymorphisms (SNPs) associated with BMI identified in a genome-wide association study (GWAS) comprising 339224 individuals. Data on outcomes, including total testosterone (TT, 199569 samples), estradiol (E 2 , 17134 samples), and sex hormone binding globulin (SHBG, 185211 samples), were sourced from the United Kingdom Biobank (UKB)., Results: In cross-sectional analysis involving 4092 males, multivariable linear regression demonstrated that each unit increase in BMI was positively correlated with an elevated risk of testosterone deficiency (TD), increased E 2 levels, and a reduced TT, SHBG, free androgen index and TT/E 2 . Subsequent quartile division of BMI revealed, through multivariable logistic regression, that higher BMI quartiles were associated with a greater TD risk, elevated E 2 levels, and reduced TT, SHBG, and TT/E 2 levels compared to quartile 1 (P for trend <0.001). In the MR analysis, a causal effect was established, with each unit increase in BMI being associated with decreased TT (β = -0.17; 95 % CI -0.24 to -0.09) and SHBG (β = -0.13; 95 % CI -0.21 to -0.05) levels., Conclusions: Our findings unveil a causal link between BMI and reduced TT and SHBG levels in males., 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 © 2024. Published by Elsevier Ltd.)

Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment., (© 2024. The Author(s).)

Previous studies have revealed an association between dietary factors and atopic dermatitis (AD). To explore whether there was a causal relationship between diet and AD, we performed Mendelian randomisation (MR) analysis. The dataset of twenty-one dietary factors was obtained from UK Biobank. The dataset for AD was obtained from the publicly available FinnGen consortium. The main research method was the inverse-variance weighting method, which was supplemented by MR‒Egger, weighted median and weighted mode. In addition, sensitivity analysis was performed to ensure the accuracy of the results. The study revealed that beef intake (OR = 0·351; 95 % CI 0·145, 0·847; P = 0·020) and white bread intake (OR = 0·141; 95 % CI 0·030, 0·656; P = 0·012) may be protective factors against AD. There were no causal relationships between AD and any other dietary intake factors. Sensitivity analysis showed that our results were reliable, and no heterogeneity or pleiotropy was found. Therefore, we believe that beef intake may be associated with a reduced risk of AD. Although white bread was significant in the IVW analysis, there was large uncertainty in the results given the wide 95 % CI. Other factors were not associated with AD in this study.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. While previous studies have indicated that albumin, the primary protein in human plasma, may exert influence on the inflammatory process and confer beneficial effects in neurodegenerative disorders, its role in the context of MS has been underexplored. Here, we aimed to explore the link between albumin and the risk of MS., Methods: Employing data from the UK Biobank, we investigated the association between baseline levels of serum and urine albumin and the risk of MS using Cox proportional hazards regression analysis., Results: A higher baseline level of serum albumin was associated with a lower risk of incident MS (HR=0.94, 95% CI: 0.91-0.98, P=7.66E-04). Subgroup analysis revealed a more pronounced effect in females, as well as participants with younger ages, less smoking and deficient levels of vitamin D. Conversely, no association was identified between baseline microalbuminuria level and risk of incident MS., Conclusion: Higher serum albumin level at baseline is linked to a reduced risk of MS. These results contribute to an enhanced understanding of albumin's role in MS, propose the potential use of albumin as a biomarker for MS, and have implications for the design of therapeutic interventions targeting albumin in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Li, Zhao and Shang.)

Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese Han and 33,224 white British participants. We identified 38 new associations in Chinese-alone analyses and 486 additional new associations in cross-ancestry meta-analyses at P < 1.46 × 10 -11 for discovery and P < 0.05 for replication. We pooled significant autosomal associations identified by single- or cross-ancestry analyses into 6,443 independent associations, which showed uneven distribution in the genome and the phenotype subgroups. We further divided them into 44 associations with different effect sizes and 3,557 associations with similar effect sizes between ancestries. Loci of these associations were shared with 15 brain-related non-imaging traits including cognition and neuropsychiatric disorders. Our results provide a valuable catalog of genetic associations for brain imaging phenotypes in more diverse populations., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp., Methods: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations., Results: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp., Conclusion: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp., (© 2024. The Author(s).)

Introduction: The impact of early-life tobacco exposure on dementia has remained unknown., Methods: Using the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all-cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted., Results: The time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk., Discussion: Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks., Highlights: Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method - the accelerated failure model - to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The UK screening and treatment of retinopathy of prematurity (ROP) updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists, following the standards of the National Institute for Health and Care Excellence. They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022, and formally published in Early Human Development in March 2023. The guidelines provide evidence-based recommendations for the screening and treatment of ROP. The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks. The treatment section covers treatment indications, timing, methods, and follow-up visits of ROP. This article interprets the guidelines and compares them with ROP guidelines/consensus in China, providing a reference for domestic peers.

Background: Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer's disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts., Methods: This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates., Results: A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels., Conclusions: These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits., (© 2024. The Author(s).)

Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public., (© 2024. The Author(s).)

Objectives: This study aimed to explore the associations between different types of meat consumption and mortality risk among people with frailty., Design: Longitudinal study., Setting and Participants: We included 19,913 physically frail participants from the UK Biobank., Measurements: We used the validated brief food frequency questionnaire (FFQ) to measure meat consumption. Baseline diet data from 2006 to 2010 were collected, and participants were followed up until March 23, 2021. Cox proportional hazards regression models were conducted to examine the associations of meat consumption with mortality risk., Results: We identified 3,622 all-cause deaths, 1,453 cancer deaths, and 1,663 cardiovascular deaths during a median follow-up time of 11.2 years. Higher consumption of unprocessed poultry (per 25 g/day increment) was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.75-0.88), cancer mortality (HR 0.84, 95% CI 0.74-0.96), and cardiovascular mortality (HR 0.72, 95% CI 0.63-0.81). Consumption of unprocessed red meat had a U-shaped relationship with mortality. Moderate consumption of unprocessed red meat 1.0-1.9 times/week was associated with a 14% (95% CI: 3 %-24%) lower risk of all-cause mortality than the lowest consumption frequency group (0-0.9 times/week). The hazard of cancer and CV mortality was also lower in the 1.0-1.9 times/week group, though the associations were not statistically significant. More frequent consumption of processed meat was associated with an increased risk of all-cause mortality (HR 1.20, 95% CI 1.07-1.34) and cardiovascular mortality (HR 1.20, 95% CI 1.02-1.42). Fish consumption was not associated with all types of mortality., Conclusions: Higher consumption of processed meat, not fish, was associated with increased all-cause and cardiovascular mortality. In contrast, higher consumption of unprocessed poultry and moderate consumption of unprocessed red meat was associated with reduced all-cause, cancer, and cardiovascular mortality. These findings warrant further investigation to establish optimal dietary patterns for frail individuals., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To investigate the longitudinal association between alcohol abstinence and accelerated biological aging among middle-aged and older adults and to explore the potential effect modifiers influencing the association., Methods: Utilizing the clinico-biochemical and anthropometric data from the baseline and first repeat survey of the UK Biobank (UKB), we employed the Klemera and Doubal method (KDM) to construct the biological age (BA) and calculate BA acceleration. Change analysis based on multivariate linear regression models was employed to explore the association between changes in alcohol abstinence and changes in BA acceleration. Age, sex, smoking status, tea and coffee consumption, and body mass index were considered as the stratification factors for conducting stratified analysis., Results: A total of 5 412 participants were included. Short-term alcohol abstinence ( β =1.00, 95% confidence interval [ CI ]: 0.15-1.86) was found to accelerate biological aging when compared to consistent never drinking, while long-term abstinence ( β =-0.20, 95% CI : -1.12-0.71) did not result in a significant acceleration of biological aging. Body mass index may be a potential effect modifier., Conclusion: Short-term alcohol abstinence was associated with accelerated biological aging, but the effect gradually diminishes over extended periods of abstinence., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objectives: Osteoporosis, a prevalent skeletal disorder characterized by reduced bone strength, is closely linked to the IGF system, crucial for skeletal metabolism. However, the precise nature of this relationship remains elusive. In this study, we employed Mendelian randomization (MR) to unravel the associations between genetically predicted serum IGF system member levels and osteoporosis., Methods: A two-sample MR approach was employed to investigate these causal associations based on two individual datasets. Predictions of 14 serum levels of IGF system members were made using 11,036,163 relevant Single Nucleotide Polymorphisms (SNPs) within a cohort of 4,301 individuals of European descent. Genetic association estimates for osteoporosis were derived from two publicly available GWAS consortia: the Finnish consortium from the FinnGen biobank, comprising 212,778 individuals of Finnish descent (3,203 cases and 209,575 controls), and the UK consortium from the UK Biobank, including 337,159 individuals of European descent (5,266 cases and 331,893 controls)., Results: According to the UK dataset, IGF-1 levels were associated with a reduced risk of osteoporosis, as indicated by the weighted median method (Odds Ratio [OR] = 0.998, 95% CI = 0.997-1.000, P = 0.032). Additionally, higher levels of IGFBP-3 were linked to a decreased risk of osteoporosis using the Inverse-Variance Weighted (IVW) method (OR = 0.999, 95% CI = 0.998-1.000, P = 0.019), and CTGF levels exhibited a negative association with osteoporosis, as determined by the weighted median method (OR = 0.998, 95% CI = 0.996-0.999, P = 0.004). In the FinnGen dataset, IGF-1 and IGFBP-3 were not identified to be associated with osteoporosis. While, IGF-LR1 levels displayed a negative association with osteoporosis, according to the MR-Egger method (OR = 0.886, 95% CI = 0.795-0.987, P = 0.036), while CYR61 was linked to an increased risk of osteoporosis based on both the weighted median and IVW methods (OR = 1.154, 95% CI = 1.009-1.319, P = 0.037, and OR = 1.115, 95% CI = 1.022-1.215, P = 0.014, respectively)., Conclusion: This study provides compelling evidence that certain IGF family members play a role in the pathogenesis of osteoporosis between different datasets, indicating population specific causal effects between IGF family and osteoporosis. Although the results from both datasets demonstrated that IGF family involved in the pathogenesis of osteoporosis, but the responding key molecules might be various among different population. Subsequent research is warranted to evaluate the potential of these biomarkers as targets for osteoporosis prevention and treatment in specific population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Zhao, Lin, Li, Zhu and Li.)

Objectives: Oral health problem is prevalent in the elderly population which is also at high risk of Parkinson's disease (PD). However, the association between self-reported oral health and PD is still unclear. We aimed to explore the association between baseline self-reported oral health (mouth ulcers, painful gums, bleeding gums, loose teeth, toothache, dentures) and future incidence of PD., Methods and Participants: Participants were enrolled in the UK Biobank from 2006 to 2010 and those without PD at baseline were included in the current study. We used Cox regression analysis to explore the question and adjusted for age, sex, body mass index, smoking, drinking, ethnicity, education, socioeconomic status, and average total household income before tax., Results: We included 421,180 participants with a mean age of 56.26 years old, and 46.5% of them were male. And 2,339 participants were diagnosed with PD in the follow-up. Mouth ulcers, loose teeth, dentures, toothache, and bleeding gums were not related to the risk of PD. Painful gums were related to a higher risk of PD (HR: 1.39, 95% CI: 1.12-1.72, p = 0.003), and similar results were reached after adjusting for gene risk (HR: 1.39, 95% CI: 1.12-1.73, p = 0.003), or source of diagnosis (HR: 1.39, 95% CI: 1.12-1.72, p = 0.002), and time of diagnosis (HR: 1.29, 95% CI: 1.03-1.63, p = 0.02)., Conclusions: Our study has demonstrated a substantial correlation between painful gums and elevated susceptibility to PD, underscoring the potential advantages of implementing oral health interventions for decreasing the risk of PD., (© 2023 S. Karger AG, Basel.)

Background: Previous research has suggested that pathogen infections may serve as potential contributors to dementia., Objective: Consequently, the study aimed to evaluate whether pathogen exposure heightens the risk of dementia., Methods: Between 2006 and 2010, a total of 8,144 individuals from the UK Biobank had data on pathogen antibodies and were included in the baseline assessment. Cox proportional hazard models were employed for the analysis., Results: Out of the 8,144 participants, 107 eventually developed dementia, while 55 participants were diagnosed with Alzheimer's disease (AD). Multivariate Cox regression analysis revealed that the levels of pathogen antibody titers of EBV and C. trachomatis were associated with an increased risk of dementia/AD. The highest quartile of EBV EBNA-1 and EBV VCA p18, and the second quartile of H. pylori VacA significantly increased the risk of dementia compared lower quartile (EBV EBNA-1: HR = 1.938, p = 0.018; EBV VCA p18: HR = 1.824, p = 0.040; H. pylori VacA: HR = 1.890, p = 0.033). Besides, the highest quartile of EBV VCA p18 had a higher risk of AD compared lower quartile (HR = 2.755, p = 0.029)., Conclusions: The study demonstrated that exposure to EBV, H. pylori, and C. trachomatis substantially elevated the risk of dementia/AD. Despite the relatively widespread occurrence of EBV infection in the population, elevated pathogen antibody titers were still found to increase the risk of dementia/AD. Besides, since C. trachomatis and C. pneumoniae are quite homologous, this study found that trachomatis (C. trachomatis/C. pneumoniae) may be significantly associated with the risk of AD/dementia.

Aims: Genetic and lifestyle factors are both major contributors to valvular heart disease (VHD). However, it is still uncertain whether genetic susceptibility alters the association between lifestyle and VHD. We aimed to investigate the association between lifestyle and VHD in different genetic risk backgrounds., Methods and Results: A prospective cohort study was carried out on 499 341 participants without VHD at baseline. The assessment of lifestyle included smoking, alcohol consumption, diet, activity, and sleep. Genetic susceptibility was separately measured by polygenic risk scores (PRSs) and family history of cardiovascular disease (CVD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) between lifestyle and VHD, as well as aortic stenosis (AS). During a median follow-up of 10.8 years, 12 983 incident VHD cases were diagnosed (incidence rate 2.46 per 1000 person-years), including 3527 AS cases (incidence rate 0.66 per 1000 person-years). The risk of VHD and AS decreased with healthier lifestyles (P value for trend <0.001). Compared to individuals with a unhealthy lifestyle, the HRs of VHD in intermediate and healthy lifestyle groups were 0.81 (0.76-0.86) and 0.81 (0.76-0.87). The negative association between healthy lifestyle and VHD events was independent of genetic risk (P for interaction between healthy lifestyle scores and PRSs/family history of CVD was 0.723/0.763). Similar findings were obtained in analyses of AS, and a stronger negative association was found., Conclusion: Our study reveals that adherence to a healthy lifestyle is significantly associated with a reduced risk of VHD especially AS, irrespective of genetic susceptibility., Summary: Based on a cohort of around 490 000 participants, the study investigated the association between lifestyle and VHD under different stratifications of genetic risk. The study found that a healthy lifestyle was associated with a lower risk of VHD, particularly AS, independent of genetic risk. Our findings suggest that advance interventions for lifestyle may be an effective way to reduce the global burden of VHD., Competing Interests: Conflict of interest: We declare that there are no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification., Methods: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections., Results: Participants aged 59 (51-64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid-base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results., Conclusions: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To investigate whether prior cholecystectomy is associated with incident osteoporosis., Background: Cholecystectomy may have consequences involving abnormal metabolism. Studies investigating the association between prior cholecystectomy and osteoporosis have yielded inconsistent results., Methods: In total, 17,603 UK Biobank participants underwent cholecystectomy, and 35,206 matched controls were included in this study. They were followed up for incident osteoporosis, which was determined using ICD-10 codes (M80-82). The association between cholecystectomy and osteoporosis was assessed using Cox proportional regression modeling. The association between osteoporosis risk and cholecystectomy was further analyzed across age, sex, serum vitamin D level, and body mass index (BMI) categories., Results: Within a median follow-up period of 13.56 years, 3,217 participants were diagnosed with osteoporosis. After adjustment for relevant confounders, prior cholecystectomy was associated with a 1.21 times higher risk of osteoporosis in women (hazard ratio (HR): 1.21 [95% CI, 1.12-1.31], p < 0.001) and a 1.45 times higher risk in men (HR: 1.45 [95% CI, 1.10-1.90], p = 0.007). In women, the association was stronger for patients who were aged 40-55 years, with BMI < 18.5 kg/m 2 , and vitamin D between 30 and 50 nmol/ml. No significant interactions between cholecystectomy and income level, education level, presence of hypertension, or diabetes were identified in either sex., Conclusions: Our findings indicated that people who underwent cholecystectomy had a higher risk of developing osteoporosis after adjustment for potential confounders. Our findings suggest that awareness of the risk of osteoporosis in patients with a history of cholecystectomy is merited., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Wang, Zhang, Wen, Long and Xia.)

Objective: To explore the association between body composition and sensorineural hearing loss (SNHL)., Study Design: Cross-sectional study, prospective study and Mendelian randomization (MR) analyses., Setting: UK Biobank., Methods: This cross-sectional study included 147,296 adult participants with complete data on body composition and the speech-reception-threshold (SRT) test. We further conducted a prospective study with 129,905 participants without SNHL at baseline and followed up to 15 years to explore the association between body composition and new-onset SNHL. Multivariable logistic regression and Cox regression models were used. Subgroup analyses stratified by age and sex were performed. We further assessed the causal association between body composition and SNHL using two-sample MR analyses., Results: Our cross-sectional study revealed that fat percentage, especially leg (odds ratio [OR] 1.46, p = .029) and arm (OR 1.43, p = .004), were significant risk factors for SNHL. However, fat-free mass, especially in the arm (OR 0.27, p < .001) and leg (OR 0.58, p < .001) showed significant protective effects against SNHL, which was substantially consistent with the results of the prospective study. In addition, we found that young women with SNHL were more susceptible to body composition indicators. However, MR analyses revealed no evidence of significant causal association., Conclusion: Fat percentage, especially in the leg and arm, was a significant risk factor for SNHL, whereas fat-free mass, especially in the leg and arm, had significant protective effects against SNHL, however, these associations may not be causal., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives: To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases., Design: Retrospective cohort study., Setting: UK Biobank., Participants: A total of 500 371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex., Exposure: Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank., Primary and Secondary Outcome Measures: The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively., Results: During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p < 0.001; male: HR=1.66, 95% CI=1.41 to 1.97, p < 0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95% CI=1.47 to 2.11, p < 0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95% CI=3.32 to 11.04, p < 0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups., Conclusion: In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Hearing impairment is common in the middle-aged population but remains largely undiagnosed and untreated. The knowledge about to what extent and how hearing impairment matters for health is currently lacking. Thus, we aimed to comprehensively examine the adverse health consequences as well as the comorbidity patterns of undiagnosed hearing loss., Study Design: Based on the prospective cohort of the UK Biobank, we included 14,620 individuals (median age 61 years) with audiometry-determined (i.e., speech-in-noise test) objective hearing loss and 38,479 individuals with subjective hearing loss (i.e., tested negative but with self-reported hearing problems; median age 58 years) at recruitment (2006-2010), together with 29,240 and 38,479 matched unexposed individuals respectively., Main Outcome Measures: Cox regression was used to determine the associations of both hearing-loss exposures with the risk of 499 medical conditions and 14 cause-specific deaths, adjusting for ethnicity, annual household income, smoking and alcohol intake, exposure to working noise, and BMI. Comorbidity patterns following both exposures were visualized by comorbidity modules (i.e., sets of connected diseases) identified in the comorbidity network analyses., Results: During a median follow-up of 9 years, 28 medical conditions and mortality related to nervous system disease showed significant associations with prior objective hearing loss. Subsequently, the comorbidity network identified four comorbidity modules (i.e., neurodegenerative, respiratory, psychiatric, and cardiometabolic diseases), with the most pronounced association noted for the module related to neurodegenerative diseases (meta-hazard ratio [HR] = 2.00, 95%confidence interval [CI] 1.67-2.39). For subjective hearing loss, we found 57 associated medical conditions, which were partitioned into four modules (i.e., diseases related to the digestive, psychiatric, inflammatory, and cardiometabolic systems), with meta-HRs varying from 1.17 to 1.25., Conclusions: Undiagnosed hearing loss captured by screening could identify individuals with at greater risk of multiple adverse health consequences, highlighting the importance of screening for speech-in-noise hearing impairment in the middle-aged population, for potential early diagnosis and intervention., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To determine the association between self-rated health (SRH) and subsequent all-cause hospitalizations in patients with bipolar disorder (BD) or major depression (MDD)., Methods: We conducted a prospective cohort study on people with BD or MDD in the UK from 2006 to 2010 using UK Biobank touchscreen questionnaire data and linked administrative health databases. The association between SRH and 2-year all-cause hospitalizations was assessed using proportional hazard regression after adjustment for sociodemographics, lifestyle behaviors, previous hospitalization use, the Elixhauser comorbidity index, and environmental factors., Results: A total of 29,966 participants were identified, experiencing 10,279 hospitalization events. Among the cohort, the average age was 55.88 (SD 8.01) years, 64.02 % were female, and 3029 (10.11 %), 15,972 (53.30 %), 8313 (27.74 %), and 2652 (8.85 %) reported excellent, good, fair, and poor SRH, respectively. Among patients reporting poor SRH, 54.19 % had a hospitalization event within 2 years compared with 22.65 % for those having excellent SRH. In the adjusted analysis, patients with good, fair, and poor SRH had 1.31 (95 % CI 1.21-1.42), 1.82 (95 % CI 1.68-1.98), and 2.45 (95 % CI 2.22, 2.70) higher hazards of hospitalization, respectively, than those with excellent SRH., Limitations: Selection bias can exist as our cohort cannot fully represent all the BD and MDD cases in the UK. Moreover, the causality is questionable., Conclusion: SRH was independently associated with subsequent all-cause hospitalizations in patients with BD or MDD. This large study underscores the need for proactive SRH screening in this population, which might inform resource allocation in clinical care and enhance high-risk population detection., Competing Interests: Conflict of interest The authors declare none., (Copyright © 2023 Elsevier B.V. All rights reserved.)