Background: While stable dietary patterns and hedonic responses in food preferences are associated with depression, whether neurobiological mechanisms mediate this relationship remains unknown. This study therefore investigates the food preference–depression associations and their potential neurostructural mediation. Methods: Over 140,000 participants were included in a longitudinal study and cross-sectional. We employed Cox regression models to examine the relationships between food preferences and depression. Half-longitudinal mediation analysis and cross-lagged models estimated the mediating roles of brain grey matter and prospective relationships with depressive symptoms. Results: We found protective effects of moderate salty, bitter and spicy preferences against depression, especially in overweight and obese participants. Further, brain structure demonstrated widespread positive correlations with both food preferences and depressive symptoms. The mediation analysis identified volumes of peripheral cortical grey matter, ventricular cerebrospinal fluid, and grey and white matter as potential mediators in the relationships between salty preferences and depression. Of these, cross-lagged models revealed the distinct directional relationships between the volume of grey matter in the VI cerebellum (vermis)/lateral occipital cortex inferior division (right) and depression, indicating that their mutual influences are mediated through different neural mechanisms. Conclusions: Moderate, but not extreme, liking of specific tastes (spicy, bitter, or salty) reflects healthier mental states. The structure of brain grey matter may mediate the relationship between salty preference and depression; also, the cerebellum together with lateral occipital regions may potentially serve as potential emotional correlates. Further neurobiological investigations are needed to confirm this pathway and inform novel therapeutic strategies for depressive disorders.

ABSTRACT Background and aims: Mental and behavioral disorders due to use of tobacco (MBDT) present a critical challenge to global health, yet modifiable lifestyle factors for reducing its risk remain poorly understood. Given that dietary fibre can affect mental health through gut-brain communication, we sought to explore how fibre intake relates to MBDT risks in smokers. Methods: We specifically evaluated the link between dietary fibre intake and MBDT within a smoking population. Utilizing the UK Biobank (UKB) database, we performed cross-sectional (N=19,943) and prospective cohort (N=19,885) evaluations applying logistic and Cox proportional hazards models, respectively. To determine potential causality, two-sample Mendelian randomization (MR) was applied, relying on GWAS summary data derived from the IEU Open GWAS Project and FinnGen repositories. Results: Cross-sectional findings indicated that individuals in the top quartile (Q4) of fibre intake exhibited decreased MBDT risks relative to the bottom quartile (Q1) (OR: 0.32, 95% CI: 0.13-0.79). Over a median observation time of 12.84 years, the prospective evaluation demonstrated a notable inverse correlation (Q4 HR: 0.46, 95% CI: 0.40-0.54). Non-linear modeling via restricted cubic splines uncovered an L-shaped dose-response curve. Furthermore, MR results confirmed a genetically predicted protective causality (IVW OR: 0.68, 95% CI: 0.49-0.95), which remained consistent across sensitivity validations. Conclusions: Among smokers, higher dietary fibre intake is robustly associated with a reduced risk of mental and behavioral disorders due to the use of tobacco, offering a modifiable dietary target for public health interventions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The North West Multi-centre Research Ethics Committee gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes UK Biobank data are available upon successful application (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). The GWAS summary statistics used in this study have been publicly released. For dietary iron intake data, please visit https://opengwas.io/datasets/. For the MBDT data, please visit https://www.finngen.fi/en/access_results.

Tobacco use was as an unhealthy lifestyle. But there were few studies about mental and behavioral disorders due to use of tobacco (MBDT). Inflammation played a role in several mental and behavioral disorders. Hence, this research investigated the association between inflammation biomarkers and MBDT. We selected 10 inflammation biomarkers including lymphocyte (LYM), neutrophil (NEU), monocyte (MON), platelet (PLT), aggregate index of systemic inflammation (AISI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), platelet-to-Lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) to explore the association between inflammation biomarkers and MBDT in a cross-section study and a dynamic cohort study. To explore the dose-response relationship between inflammation biomarkers MBDT, the restricted cubic spline was performed. Besides, the stratified analyses and sensitive analyses were used to test the stability of results. According to results of cohort study, all inflammation biomarkers were significantly associated with the risk of MBDT. The changes in HRs (95

Background:Some cross-sectional have found the negative association between dietary biotin intake and anxiety and depression symptoms. However, there is still a lack of cohort study in this field. So we conduct this prospective cohort study to investigate the association between dietary biotin intake and anxiety and depression, evaluate their dose-response relationship and the mediating role of inflammation in this process. Methods:A total of 144,439 UK Biobank participants without baseline anxiety or depression were included. Dietary biotin intake was derived from the 24-h Oxford WebQ data, and anxiety and depression were defined in accordance with the ICD-10 criteria. Cox proportional hazards models and restricted cubic splines (RCS) were used to evaluate longitudinal associations. The Karlson-Holm-Breen method was used to examine the mediating effect of inflammation. Results:A total of 144,439 participants were included in this study with a median follow-up of 14.06 years. Compared to Q1 group, dietary biotin intake was associated with a reduced risk of anxiety or depression (HR: 0.86 [0.82, 0.91] for Q2; HR: 0.84 [0.79, 0.88] for Q3; HR: 0.86 [0.81, 0.91] for Q4). Similar results were also found in anxiety, depression, and their comorbidity. RCS existed an approximately "L-shaped" dose-response relationship between biotin and both anxiety and depression. Except for depression and comorbidity, both single mediating indicators and composite mediating indicators played a partial mediating role in the course of this. Conclusion:Dietary biotin intake exhibited an approximately L-shaped nonlinear relationship with anxiety and depression risk, where risk decreased with increasing intake up to a moderate threshold, beyond which no further reduction was observed. This association may be partially mediated by inflammation.

Background Previous studies have shown that tea consumption frequency or sleep quality is independently associated with cognitive function, but the combined association remains unclear. Objective To investigate the individual and combined associations between tea consumption frequency and sleep quality with cognitive function and analyze whether this association is modified by gender and age. Methods The cross-sectional study involved 646 participants from 17 villages in Jimo District, Qingdao, in 2022. Data on tea consumption frequency were collected via a questionnaire. Cognitive function and sleep quality were assessed through the Montreal Cognitive Assessment and Pittsburgh Sleep Quality Index, respectively. Linear regression models were used to analyze associations, with a combined variable for tea consumption frequency and sleep quality constructed to evaluate their combined association. Stratified analysis and interaction tests assessed the moderating effects of gender and age. Results Higher consumption frequency of green tea (β (95% CI): 0.97 (0.23, 1.70)) or black tea (β (95% CI): 0.78 (0.08, 1.48)) was positively associated with cognitive function. Moreover, higher consumption frequency of green tea combined with good sleep quality was significantly associated with optimal cognitive function (β (95% CI): 1.17 (0.10, 2.31)). Stratified analysis revealed no significant modifying effects of gender or age on the aforementioned associations. Conclusion Increased consumption frequency of green tea, alongside maintaining good sleep quality, is associated with enhanced cognitive function. These findings highlight the value of modifiable lifestyle factors in promoting cognitive health.

Background: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) frequently coexist, yet the shared genetic variants underlying these conditions remain poorly understood. This study aimed to investigate shared genetic variants underlying lung function and glucose levels in middle-aged Chinese twins. Methods: In this exploratory analysis, we reanalyzed genotype data from a previously published northern Chinese twin sample, including 139 dizygotic and 238 monozygotic twin pairs from the Qingdao Twin Registry. Lung function traits (FEV1, FVC, and FEV1/FVC) and fasting plasma glucose (FPG) were jointly analyzed using a twin-based bivariate genome-wide association approach, followed by functional annotation and gene-based analyses. Variants showing suggestive associations were further examined in an independent UK Biobank Chinese sample. Results: A significant negative correlation between the FEV1/FVC ratio and FPG was revealed. The analysis identified 29 SNPs reaching genome-wide significance, with association signals primarily clustering at the 2q33.1 locus. Functional annotation indicated that most associated variants were non-coding, with several SNPs overlapping regulatory elements annotated to the SPATS2L locus. Gene-based analysis further supported the involvement of SPATS2L in the shared genetic architecture of the two traits. In the validation analysis, seven variants at the 2q33.1 locus showed nominal associations with consistent effect directions. Conclusions: This exploratory bivariate analysis provides evidence supporting shared genetic variants underlying pulmonary function and glucose regulation and offers insight into the genetic basis of COPD-T2DM comorbidity.

This study investigated the relationships of total dietary grain fibre (TGF) and its two subtypes (whole grain fibre (WGF) and refined grain fibre (RGF)) with essential hypertension (EHP) in a large-scale prospective cohort study. The participants were recruited by UK Biobank. Dietary grain fibre was assessed using the baseline touchscreen food-frequency questionnaire. New-onset EHP was defined by International Classification of Disease version 10. Cox proportional hazards model and restricted cubic spline (RCS) analysis were utilized to examine the associations of TGF and its subtypes with EHP. Additionally, mediation analysis was applied to assess whether the triglyceride-glucose (TyG) index and inflammatory index score (INFLA-score) mediated these associations. Among 60,315 participants without prior hypertension, 3,651 (6.05%) developed EHP over a median follow-up of 10.3 years, with an incidence density of 6.08 per 1,000 person-years. The adjusted hazard ratios for Q4 compared with Q1 were 0.828 (95% CI: 0.750, 0.914) for TGF and 0.842 (95% CI: 0.767, 0.936) for WGF. RCS analysis confirmed inverse relationships for TGF and WGF with EHP risk. But RGF showed no significant association with EHP. The TyG index and INFLA-score partially mediated the associations of TGF and WGF with EHP, with mediation proportions of 4.2% and 3.3% for TGF, and 4.9% and 5.2% for WGF, respectively. Jointly, TyG index and INFLA-score together mediated 5.6% between TGF and EHP, and 7.4% between WGF and EHP. In conclusion, higher intake of TGF and WGF reduce EHP risk, and this effect is only partly mediated by TyG index and INFLA-score.

OBJECTIVES:To investigate the longitudinal association between Pain-Insomnia-Depression Syndrome (PIDS) and cognitive decline, assess the dose-response relationship associated with cumulative symptom load, and examine the potential protective role of healthy lifestyles. DESIGN:Population-based prospective cohort study. SETTING AND PARTICIPANTS:A total of 7565 participants aged 50 years and older from the English Longitudinal Study of Ageing, with a follow-up period of up to 9 years. METHODS:PIDS burden was defined in 2 complementary ways: the presence of PIDS (all 3 conditions present) and cumulative symptom load (ranging from 0 to 3 conditions). Cognitive domains, including episodic memory, executive function, and temporal orientation, were assessed using standardized z scores. Lifestyle factors (smoking, alcohol intake, physical activity, diet) were combined into a composite score and categorized as healthy (3-4 factors) or unhealthy (0-2 factors). Linear mixed-effects models were used to estimate baseline differences and rates of cognitive change. RESULTS:Participants with PIDS exhibited significantly lower baseline global cognitive function (β, -0.171; 95% CI, -0.245 to -0.098) and experienced a more rapid cognitive decline (β, -0.050 SD/year; 95% CI, -0.069 to -0.031). For cumulative symptom load, a clear dose-response pattern was observed in global cognition: 1 symptom predicted a decline of β, -0.019 SD/year; 95% CI, -0.030 to -0.008, 2 symptoms predicted β, -0.031 SD/year; 95% CI, -0.044 to -0.018, and 3 symptoms β, -0.064 SD/year; 95% CI, -0.084 to -0.044. Notably, adherence to healthy lifestyles attenuated these negative effects, with PIDS participants maintaining healthy lifestyles exhibiting a slower rate of cognitive decline (β, 0.055 SD/year; 95% CI, 0.015 to 0.095). CONCLUSION AND IMPLICATIONS:PIDS and higher cumulative symptom load are associated with accelerated cognitive decline in middle-aged and older adults. Healthy lifestyle adherence mitigates these effects, underscoring integrated strategies combining symptom management with lifestyle interventions to reduce dementia risk.

BackgroundAn association exists between oral health problems and inflammatory bowel disease (IBD). However, few studies have considered comprehensive oral health problems and the concurrent presence of multiple oral health problems in relation to IBD. Additionally, the role of inflammatory responses as a mediator in this relationship remains unexplored. This study aimed to investigate association between oral health problems and IBD utilizing data from the UK Biobank.MethodsOral health were assessed via self-reported. IBD was defined by disease classification codes from the International Classification of Diseases-10. Cox regression models were employed to analyze the relationships between oral health problems and IBD, using mediation analysis to investigate the role and effect size of inflammatory indicators in this association.ResultsAmong 412,134 participants, mouth ulcers (HR: 1.25, 95% CI: 1.02-1.53), painful gums (HR: 1.50, 95% CI: 1.12-2.03), and dentures (HR: 1.30, 95% CI: 1.10-1.53) linked to Crohn’s disease (CD) risk. Mouth ulcers (HR: 1.16, 95% CI: 1.01-1.34) and dentures (HR: 1.18, 95% CI: 1.05-1.33) linked to ulcerative Colitis (UC) risk. Having two (HR: 1.29, 95% CI: 1.02-1.63)/three (HR: 1.69, 95% CI: 1.14-2.49)/more than three (HR: 2.13, 95% CI: 1.20-3.78) oral health problems correlated with CD risk, with more oral health problems correlating with higher CD risk (P for trend < 0.001). Low-grade inflammation index (INFLA-score) positively mediated the association between painful gums (proportion mediated=3.09%)/dentures (proportion mediated=5.40%) and CD.ConclusionsMouth ulcers and dentures may increase the risk of CD and UC, while painful gums associates with CD. More oral health problems link to higher CD risk. Inflammatory responses partially mediating the association between painful gums/dentures and CD.

Observational studies have explored the association between depressive symptoms and cognitive function, but cannot determine causality. This study aims to investigate this association and assess its causality by combining cross-sectional analysis with bidirectional Mendelian randomization (MR). The cross-sectional study involved 438 older individuals from 17 villages in Jimo District, Qingdao, in 2024. We employed Poisson regression and linear regression to investigate the relationship between depressive symptoms and cognitive function, stratified by gender and age. Furthermore, two-sample bidirectional MR analysis was utilized to infer causal relationships between depression and cognitive performance, and sensitivity analysis were conducted to verify the robustness of the results. Cross-sectional analysis revealed a significant association between depressive symptoms status and higher prevalence of mild cognitive impairment (RR (95% CI): 1.28 (1.02, 1.60), P = 0.032). Concurrently, depressive symptoms status exhibited a negative correlation with lower cognitive function scores (β (95% CI): -1.23 (-2.46, 0.00), P = 0.049). The association was not affected by gender and age group. MR analysis provided suggestive evidence for a potentially negative causal relationship of depression on cognitive performance (IVW, β (95% CI): -5.72(-9.78, -1.66), P = 0.025). In conclusion, this study provided suggestive evidence for a potentially negative causal relationship between depressive symptoms and cognitive decline, indicating that preventing and treating depression may help delay cognitive decline.

Obesity represents a major global public health concern. Body fat percentage (BF%) is a key indicator for assessing adiposity and provides a more precise estimation of obesity-related health risks compared to the traditional body mass index (BMI). Accumulating evidence suggests that BF% is influenced by both genetic and environmental factors. However, most genetic studies on BF% have been conducted in European and American population, with limited data available from Chinese cohorts. To address this gap, a classical twin study was conducted using data from the Qingdao Twin Registry in China to estimate the heritability of BF% adjusted for age, sex, and BMI. This study included Han Chinese twins registered in the Qingdao Twin Registry. This study included 344 middle and old-aged Chinese twin pairs (217 monozygotic and 127 dizygotic). comprising 327 males and 361 females. The median age of participants was 50 (interquartile range [IQR]:12) years, with BF% of 27.6 (11.4) %. Model fitting indicated that the best-fitting model was AE model. The additive genetic effect (A) accounted for 54% (95% CI [44, 59) of the total variance, while unique environmental effect (E) contributed 46% (95% CI [37, 56]). In conclusion, this twin-based study provides robust evidence for a moderate genetic contribution (heritability = 54%) to BF% in a middle- and old-aged Qingdao population.

Previous studies mainly focused on grip strength at a single timepoint, but evidence is scarce on the association between changes in grip strength (HGS) and risk of incident cardiovascular disease (CVD). The data were sourced from UK Biobank. HGS was measured by trained staff with calibrated Jamar J00105 hydraulic hand dynamometer. HGS changes were measured by combining HGS at baseline and imaging visit (2014+), defined in three methods below: changes in standardized HGS (reference, decline, stable high, and stable low), changes in dichotomous HGS (normal/normal, weakness/normal, normal/weakness, and weakness/weakness), and annual rate of change in HGS (continuous). The outcome of interest was incidence of CVD. Cox regression was used to examine the association of changes in HGS with risk of CVD incidence. In the current study, the mean (SD) age was 54.4 (7.5) years and 47.4

The triglyceride-glucose (TyG) index is a reliable composite marker of insulin resistance, which holds important clinical significance. Existing studies have predominantly focused on identifying TyG index-related genetic loci and single-nucleotide polymorphism (SNP)-based polygenic risk scores, however, the overall contribution of genetic factors to TyG index variation at the population level is still unclear. To address this gap, we conducted a classic twin study using data from the Qingdao Twin Registry in China. The study included 381 middle-aged and older Chinese twin pairs (241 monozygotic and 140 dizygotic), comprising 370 males and 392 females. The median age of participants was 50 (interquartile range: 12) years. Structural equation modeling was applied to estimate the heritability of the TyG index after adjusting for age, gender, and body mass index (BMI). Model fitting identified the AE model as the best-fitting one. Additive genetic effects (A) accounted for 60.48% (95% CI [52.46, 67.24]) of the total variance, while unique environmental effects (E) explained 39.52% (95% CI [32.76, 47.54]). A sex-limitation model was subsequently used to test for sex differences in TyG. The results showed that heritability was higher in females (67.2%) than in males (54.0%). This twin-based study provides robust evidence for a moderate‑to‑high heritability of the TyG index in a Northern Chinese population, underscoring the substantial genetic contribution to this composite insulin resistance marker. Notably, the sex difference in heritability reflects larger unique environmental variance in males, highlighting the differential contribution of environmental factors across sexes.

BACKGROUND & AIMS:Whether healthy dietary patterns can reduce mortality and extend life expectancy across different frailty status remains unclear. We aimed to investigate the associations of four dietary patterns with mortality and life expectancy both in the overall population and by frail status. METHODS:We included 208,379 participants from the UK Biobank. Dietary intake was collected by the 24-h dietary recall assessments. Dietary patterns were assessed using previously established indices: alternative Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH), Plant-based Diet Index (PDI), and Planetary Health Diet Index (PHDI). Frailty status was defined by Fried's phenotype and classified into robust, prefrailty, and frailty. Cox proportional hazards models and flexible parametric survival models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between dietary patterns and mortality and life expectancy. RESULTS:After a median follow-up of 13.42 years, 12,571 deaths occurred. Participants with the highest adherence to a healthy pattern exhibited reduced all-cause mortality (HR ranged from 0.76 to 0.88) and longer life expectancy (years of life gained ranged from 1.84 to 3.16). The protective effects were consistent across different frailty status, and a more substantial prolongation of life was observed in frail individuals. Taking aMED as an example, the HRs and 95% CIs of mortality for the highest tertile of adherence versus the lowest were 0.80 (0.75-0.86) in robust individuals, 0.76 (0.70-0.82) in pre-frail individuals, and 0.65 (0.50-0.86) in frail individuals, and life expectancy gains were 2.45 (2.03-2.87), 3.27 (2.72-3.82), and 5.57 (3.19-7.95) years, respectively. Women had a higher overall life expectancy than men, whereas men showed greater life expectancy gains from dietary adherence. CONCLUSION:Higher adherence to aMED, DASH, PDI, and PHDI could reduce all-cause mortality and extend life expectancy regardless of frailty status.

OBJECTIVE:This study aimed to estimate the relative contributions of genetic and environmental factors on acquired tooth loss among middle-aged and older twins in Qingdao, China. METHODS:A total of 377 complete twin pairs (240 monozygotic, 137 dizygotic) were recruited from the Qingdao Twin Registry in China, and acquired tooth loss was recorded through structured interviews. Heritability of acquired tooth loss was estimated using correlation analysis and structural equation model, adjusting for age and sex. RESULTS:The median age of the twins was 50 years (IQR: 46-57). The polychoric correlations for monozygotic twins (0.67; 95% CI: 0.55-0.78) were more than twice as high as that for dizygotic twins (0.25; 95% CI: 0.03-0.48). Therefore, we fitted an additive, dominant, and unique environmental factors model and its nested submodels. Based on the Akaike information criterion, the additive and unique environmental factors model was selected as the preferred model. After adjusting for age and sex, the model indicated that 56.51% (95% CI: 43.21%-69.81%) of the variance in acquired tooth loss was attributable to additive genetic factors, and 43.49% (95% CI: 30.20%-56.79%) to unique environmental influences. CONCLUSION:This study demonstrated that variation in acquired tooth loss is influenced by both additive genetic and unique environmental factors. These findings may assist in developing strategies for tooth loss prevention and oral health maintenance.

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic disease, but it remains unclear whether it is related to dietary folate. This research sought to investigate the association between dietary folate and MASLD. Methods This cohort study utilized the UK Biobank (UKB) database (N = 58,047). Dietary folate intake was assessed using an online dietary questionnaire, and MASLD was ascertained through International Classification of Diseases, Tenth Revision (ICD-10). Cox proportional hazard regression, mediation analysis and restricted cubic splines (RCS) were employed to investigate the association and dose-response relationship between dietary and MASLD. The stability of findings was verified by stratified analyses and sensitivity analyses. Results Dietary folate intake was observed to be negatively associated with MASLD in cohort studies. During a median follow-up of 12.18 years, 691 cases of MASLD occurred. The risk of MASLD decreased by 24% (HR = 0.76, 95% CI: 0.59–0.97) among the participants in the highest dietary folate intake relative to lowest quartile. The protective effect was more pronounced in participants aged < 60 years (HR = 0.63, 95% CI: 0.45–0.89), male (HR = 0.63, 95% CI: 0.44–0.89), and obese participants (HR = 0.68, 95% CI: 0.48–0.95). The research results remained robust in the sensitivity analyses that excluded participants with ≤ 2 years of follow-up time, extremely folate intake, and other conditions. C-reactive protein (CRP) explained 6.56% of the association between dietary folate and MASLD. The dietary folate intake had an L-shaped relationship with the risk of MASLD (P for nonlinearity = 0.003). Conclusions Moderate folate intake (approximately 300 µg) may reduce the risk of MASLD, suggesting that promoting folate-rich diets may be a viable and cost-effective strategy for MASLD prevention.

The baseline heritability of the newly defined metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. Given that sex and alcohol consumption are well-recognized determinants of fatty liver disease, it is important to understand whether they are also associated with variation in its underlying genetic susceptibility. We aimed to quantify the baseline heritability and investigate these potential effects in a classical twin study of 710 Chinese adults using structural equation modeling. We observed a baseline narrow-sense heritability (A) of 0.57 (95% CI 0.46-0.67) in the lower alcohol intake group. This genetic contribution was not uniform and showed a potential difference by sex, with heritability tending to be higher in females (0.63) than in males (0.30). Furthermore, the genetic architecture appeared to vary across alcohol exposure levels. In contrast to the additive (AE) model observed in lower drinkers, the higher alcohol intake group was better fitted by a dominant/non-additive (DE) model, yielding a broad-sense heritability (D) of 0.60 (95% CI 0.34-0.77). In conclusion, our findings suggest that the genetic architecture of MASLD may vary according to sex and alcohol consumption, highlighting potential gene-environment interactions and the context-dependent nature of genetic susceptibility. These results may have implications for future risk stratification and targeted prevention strategies.

Frailty state is dynamic and reversible, but there is a lack of clarity about the patterns of frailty transition and its influencing factors. This study aimed to investigate frailty transitions and the impact of sociodemographic and behavioral factors on these transitions in Chinese middle-aged and older adults. We used five-wave data from the China Health and Retirement Longitudinal Study (CHARLS), and 20,140 Chinese adults aged ≥ 45 years were included. Frailty was assessed using a 35-item frailty index. A multi-state Markov model was used to systematically analyze the transition patterns of frailty states (robust, prefrail, frail) and death, and to explore the associations of sociodemographic and behavioral factors with frailty transitions. Among the 20,140 participants at baseline, the proportions of robust, prefrailty, and frailty were 30.4

BACKGROUND AND OBJECTIVES:This cross-sectional study explored the association between dietary patterns and depressive symptoms in middle-aged and older individuals in China. METHODS AND STUDY DESIGN:A total of 2,956 individuals aged 45-74 years were included in the current data analysis, based on a community-based cross-sectional study from Qingdao, China. Data for this study were derived from field surveys conducted from August 2009 to November 2010. Their mean age was 57.2 ± 8.46 years, and 62.4% were women. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire (SQFFQ). Dietary patterns were derived using principal component analysis. Depressive symptoms were assessed using the validated Zung Self-Rating Depression Scale. Logistic regression and restricted cubic spline analyses were conducted to examine the association between dietary patterns and depressive symptoms. RESULTS:Of the participants, 12.4% had depressive symptoms. These participants were younger, were more likely to be smokers, had a higher body mass index, and had lower income and education levels compared with individuals without depressive symptoms. Four dietary patterns were identified: Balanced, Animal-Pickled vegetables, High sugar-Alcohol, and Animal-Seafood-Egg dietary patterns. The Balanced (odds ratio = 0.53, p < 0.01) and Animal-Seafood-Egg (odds ratio = 0.74, p < 0.01) dietary patterns were negatively associated with depressive symptoms, whereas the Animal-Pickled vegetables dietary pattern was positively associated with depressive symptoms. No significant association was observed for the High sugar-Alcohol dietary pattern. Subgroup analysis revealed stronger inverse effects of Balanced and Animal-Seafood-Egg dietary patterns in women younger than 60 years, nonsmokers, and urban residents compared with in their counterparts. Sensitivity analysis confirmed stability across the continuous and quartile-based variables. CONCLUSIONS:The Balanced and Animal-Seafood-Egg dietary patterns were associated with lower odds of depressive symptoms, whereas the Animal-Pickled vegetables dietary pattern was associated with higher odds of depressive symptoms.

Hyperuricemia is a common metabolic disorder and has become a global health concern. This study investigated the association between DNA methylation (DNAm) and serum uric acid (SUA) by conducting an epigenomewide association study (EWAS) in Chinese monozygotic (MZ) twins. Genomewide DNAm of 50 MZ twin pairs was profiled using the Infinium MethylationEPIC v2.0 BeadChip (935K). Generalized estimating equations (GEE) were used to examine the association between DNAm and SUA. Causal relationships between DNAm and SUA were assessed using ICE FALCON approach. Associations between mRNA expression and SUA were further assessed. Finally, candidate genes identified through epigenomewide association study (EWAS), causal inference, and gene expression analyses were validated in a longitudinal twin study. We identified 70 CpGs, mapping to genes such as DOK6 and NGLY1, significantly associated with SUA (Bonferroni correction p < 5.8 × 10-8). Causal analyses revealed one CpG with a causal effect of DNAm on SUA, 22 CpGs with causal effects of SUA on DNAm, and 33 CpGs showing bidirectional causality. Eleven genes displayed expression levels associated with SUA. DOK6, NGLY1, PKM, and SLC44A1 were selected as candidate genes, all of which showed unidirectional causal effect of SUA on DNAm. In the longitudinal analysis, baseline SUA levels (2012-13) were associated with subsequent DNAm levels in DOK6 and NGLY1 genes (2023-24). In conclusion, we found that SUA levels may influence DNAm variations, particularly at CpG loci within the DOK6 and NGLY1 genes. These findings provide key clues for future investigations into the mechanisms linking SUA with its epigenetic regulatory pathways.