An Atlas on Multitudinous Risk Factors Associated with Incident Hypertension: Comprehensive Exposome-Wide Association and Wide-angled Genetic Analyses.

BACKGROUND: Despite numerous risk factors being associated with hypertension, the breadth of research remains constrained, with a notable absence of systematic, data-driven exploration into established and novel factors across a broad spectrum of exposures. This study aims to construct an atlas on known and emerging factors for hypertension through comprehensive epidemiological and genetic analyses. METHODS: We conducted exposome-wide association studies (ExWAS) via Cox regression models on two equally sized datasets for discovery and replication in UK Biobank, a large prospective cohort study. A maximum of 10,806 exposome variables were included in ExWAS and were grouped into 13 categories: genomics, sociodemographic, lifestyle, physical measure, biomarkers, medical history, imaging markers, sex-specific factors, psychosocial factors, cognitive function indicators, local environment, family history, and early life factors. The credibility of epidemiological associations was assessed through meta-analyses. The genetic underpinnings were explored through linkage-disequilibrium score regression (LDSC), quantifying global genetic correlation. Two-sample Mendelian randomization (MR) studies were conducted to investigate the causal effects of each exposure on hypertension, with co-analyses undertaken to identify associations supported by both epidemiological and genetic evidence. RESULTS: This study included 214,957 UK Biobank participants, hypertension-free at baseline. In our ExWAS analyses, 964 significant exposome variables were replicated. In meta-analyses, 462 were backed by convincing and highly suggestive evidence. Among 10,765 exposures in LDSC, 1923 had global genetic correlations with hypertension. The MR analyses yielded robust evidence for a causal relationship with 125 phenotypes, probable evidence for 270 phenotypes, and suggestive evidence for 718 phenotypes. Co-analyses identified 146 associations supported by strong epidemiological and genetic evidence. These primarily encompassed traits like anthropometry, lung function, lipids, and factors such as urate and walking pace. This coverage further extended from well-studied factors (like BMI and physical activity) to less explored exposures (including high light scatter reticulocyte count and age at first live). All study results are compiled in a webserver for user-friendly exploration of exposure-hypertension associations. CONCLUSION: This study provides an atlas on established and novel risk factors for hypertension, underpinned by epidemiological and causal evidence. Our findings present a multiple perspective to prioritize hypertension prevention strategies, encompassing modifiable risk factors like television watching time and walking pace. The study also emphasized the roles of urate in hypertension pathogenesis. Consequently, our study may serve as a critical guide for hypertension prevention and bear significant clinical implications.

Researchers have created a comprehensive map that identifies and analyses a wide array of risk factors linked to the development of high blood pressure, using extensive data from the UK Biobank. The study revealed 964 significant factors related to lifestyle, environment, and genetics that could influence the risk of developing hypertension, with 462 of these factors showing strong evidence of a link.Key lifestyle-related findings include the impact of behaviors such as television watching and walking pace on hypertension risk, suggesting that modifiable habits can be targeted for prevention strategies.

Association between chronic pain and risk of cardiometabolic multimorbidity: a prospective cohort study.

BACKGROUND: Although chronic pain was deleteriously related to single cardiometabolic diseases, the relationship between chronic pain and cardiometabolic multimorbidity remains unclear. The purpose of this study was to investigate the association between chronic pain with the risk of cardiometabolic multimorbidity. METHODS: A prospective cohort study included 452 818 participants who were free of cardiometabolic multimorbidity at baseline. Chronic pain was assessed in diverse anatomical sites including the head, face, neck/shoulder, stomach/abdominal area, back, hip and knee or 'all over the body'. Participants were classified into six groups according to the amount of chronic pain sites: no chronic pain, chronic pain at one, two, three and four or more sites, and those reporting pain 'all over the body'. Cardiometabolic multimorbidity was defined as the occurrence of at least two cardiometabolic diseases, involving type 2 diabetes, ischaemic heart disease and stroke. RESULTS: After a median follow-up of 13.7 years, 4445 participants developed cardiometabolic multimorbidity. Compared with individuals without chronic pain, those experiencing chronic pain in four or more sites were associated with a 1.82-fold (HR: 1.82, 95% CI: 1.61, 2.06) higher risk of cardiometabolic multimorbidity. Pain distributed 'all over the body' was associated with a 59% (HR: 1.59, 95% CI: 1.30, 1.93) increased risk of cardiometabolic multimorbidity Additionally, individuals who had chronic pain in both the head and stomach/abdomen showed the highest risk with cardiometabolic multimorbidity (HR: 1.88, 95% CI: 1.60, 2.20). CONCLUSIONS: Our findings suggested that there was an elevated risk of cardiometabolic multimorbidity associated with an increased amount of chronic pain sites.

Consumption of sugary beverages, genetic predisposition and the risk of depression: a prospective cohort study.

Background: The associations between sugary beverages and genetic predisposition to depression risk remain unclear. Aims: This study aimed to investigate the associations of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with depression and to assess whether these associations were modified by genetic predisposition. Methods: We used data from the UK Biobank of 180 599 individuals aged 39-72 years who were depression-free at baseline. Dietary intake of SSBs, ASBs and NJs was accessed by a 24-hour dietary recall between 2009 and 2012. The Polygenic Risk Score for depression was estimated and categorised as low (lowest tertile), intermediate (tertile 2) and high (highest tertile). Cox proportional hazard and substitution models were conducted to evaluate hazard ratios (HRs) and 95% CIs. Results: Over the 12-year follow-up, 4915 individuals developed depression. Higher consumption (>2 units/day) of SSBs (HR: 1.26, 95% CI 1.12 to 1.43) and ASBs (HR: 1.40, 95% CI 1.23 to 1.60) were both associated with an increased risk of depression. However, moderate consumption (>0-1 units/day) of NJs was associated with a lower risk of depression (HR: 0.89, 95% CI 0.83 to 0.95). Furthermore, genetic predisposition did not modify these associations (p interaction>0.05). In substitution models, the HRs for depression risk were 0.94 (95% CI 0.89 to 0.99) and 0.89 (95% CI 0.85 to 0.94), respectively, when 1 unit/day of SSBs or ASBs was replaced by an equivalent intake of NJs. Conclusions: Higher consumption of SSBs and ASBs was associated with an increased risk of depression; in contrast, moderate consumption of NJs was inversely associated with a lower risk of depression. In theory, substituting SSBs and ASBs with NJs would suppose a reduction of depression risk.

Association of Domestic Water Hardness with All-Cause and Cause-Specific Cancers: Evidence from 447,996 UK Biobank Participants.

BACKGROUND: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants investigation. OBJECTIVE: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers. METHODS: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaCO3 concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors. RESULTS: Over a median follow-up of 13.6 y (range: 12.7-14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed (p for nonlinearity <0.001). In comparison with individuals exposed to soft water (0-60mg/L), the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause cancer were 1.00 (95% CI: 0.98, 1.02) for those exposed to moderate hard water (>60-120mg/L), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water (>120-180mg/L) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (>180mg/L). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer. DISCUSSION: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. https://doi.org/10.1289/EHP13606.

Accelerometer-derived physical activity and mortality in individuals with type 2 diabetes.

Physical activity (PA) has been shown to reduce diabetes mortality, but largely based on imprecise self-reported data, which may hinder the development of related recommendations. Here, we perform a prospective cohort study of 19,624 individuals with type 2 diabetes (T2D) from the UK Biobank with a median follow-up of 6.9 years. Duration and intensity of PA are measured by wrist-worn accelerometers over a 7-day period. We observe L-shaped associations of longer duration of PA, regardless of PA intensity, with risks of all-cause and cancer mortality, as well as a negatively linear association with cardiovascular disease mortality. 12.7%, 15.8%, and 22.3% of deaths are attributable to the lowest level of light-intensity, moderate-intensity PA, and vigorous-intensity PA, respectively. Collectively, our findings provide insights for clinical guidelines that should highlight the potential value of adherence to greater intensity and duration of PA for patients with T2D.

Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.

Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.

High-performance presurgical differentiation of glioblastoma and metastasis by means of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics.

OBJECTIVES: To evaluate the performance of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics in distinguishing between glioblastoma (Gb) and solitary brain metastasis (SBM). MATERIALS AND METHODS: In this retrospective study, NODDI images were curated from 109 patients with Gb (n = 57) or SBM (n = 52). Automatically segmented multiple volumes of interest (VOIs) encompassed the main tumor regions, including necrosis, solid tumor, and peritumoral edema. Radiomics features were extracted for each main tumor region, using three NODDI parameter maps. Radiomics models were developed based on these three NODDI parameter maps and their amalgamation to differentiate between Gb and SBM. Additionally, radiomics models were constructed based on morphological magnetic resonance imaging (MRI) and diffusion imaging (diffusion-weighted imaging [DWI]; diffusion tensor imaging [DTI]) for performance comparison. RESULTS: The validation dataset results revealed that the performance of a single NODDI parameter map model was inferior to that of the combined NODDI model. In the necrotic regions, the combined NODDI radiomics model exhibited less than ideal discriminative capabilities (area under the receiver operating characteristic curve [AUC] = 0.701). For peritumoral edema regions, the combined NODDI radiomics model achieved a moderate level of discrimination (AUC = 0.820). Within the solid tumor regions, the combined NODDI radiomics model demonstrated superior performance (AUC = 0.904), surpassing the models of other VOIs. The comparison results demonstrated that the NODDI model was better than the DWI and DTI models, while those of the morphological MRI and NODDI models were similar. CONCLUSION: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM. CLINICAL RELEVANCE STATEMENT: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM, and radiomics features can be incorporated into the multidimensional phenotypic features that describe tumor heterogeneity. KEY POINTS: • The neurite orientation dispersion and density imaging (NODDI) radiomics model showed promising performance for preoperative discrimination between glioblastoma and solitary brain metastasis. • Compared with other tumor volumes of interest, the NODDI radiomics model based on solid tumor regions performed best in distinguishing the two types of tumors. • The performance of the single-parameter NODDI model was inferior to that of the combined-parameter NODDI model.

Night shift work, genetic risk, and the risk of depression: A prospective cohort study.

BACKGROUND: Genetic factors and night shift work both contribute to the risk of depression, but whether the association of night shift work with depression varies by genetic predisposition remains unclear. OBJECTIVES: To assess whether night shift work is associated with a higher risk of depression regardless of genetic predisposition. METHODS: We used data from the UK biobank of 247,828 adults aged 38-71 free of depression at baseline from March 13, 2006, to October 1, 2010. Genetic predisposition to depression was assessed using polygenic risk scores (PRS) weighted sums of genetic variant indicator variables and classified as low (lowest tertile), intermediate (tertile 2), and high (highest tertile). Night shift work exposures were collected using a touchscreen questionnaire and were divided into four categories. RESULTS: After a median follow-up of 12.7 years, 7315 participants developed depression. Compared with day workers, HRs (95 % CIs) of depression were 1.28 (1.19-1.38) for shift work, but never or rarely night shifts, 1.32 (1.20-1.45) for irregular night shifts, and 1.20 (1.07-1.34) for permanent night shifts. Considering lifetime employment and compared with never shift workers, >8 nights/month (HR: 1.40; 95 % CI: 1.19-1.66) and <10 years (HR: 1.30; 95 % CI: 1.09-1.54) of night shift work were associated with a higher risk of depression. In joint effect analyses, compared to participants with low genetic predisposition and day workers, the HRs (95 % CIs) of depression were 1.49 (1.32-1.69) in those with high genetic predisposition and shift work, but never or rarely night shifts, and 1.36 (1.20-1.55) for those with high genetic predisposition and irregular/permanent night shifts. In addition, there was neither multiplicative nor additive interaction between genetic predisposition and night shift work on the risk of depression. CONCLUSIONS: Night shift work was associated with an increased risk of depression regardless of genetic risk.

Hearing disorders, genetic predisposition, and risk of new-onset atrial fibrillation: A prospective cohort study in the UK biobank.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Hearing impairment has been linked to several cardiovascular diseases. However, the association between hearing disorders, genetic predisposition, and new-onset AF remains largely unknown. METHODS: A total of 476,773 participants (mean age 56.5 years) free of AF at baseline (from 2006 to 2010) were included from the UK Biobank study. The presence of hearing disorders including hearing difficulty and tinnitus was self-reported through the touchscreen questionnaire. AF was defined using ICD-10 code: I48 and was followed till February 1st. 2022. The Cox model was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI). RESULTS: During a median follow-up of 13.0 years, the AF incidence rate was 2.9 per 1000 person-years. After adjustments for potential confounders, the presence of hearing difficulty (HR, 1.35; 95% CI: 1.32-1.39) and the use of hearing aid (1.45; 1.37-1.53) were significantly associated with risk of new-onset AF. Compared to individuals without tinnitus, the AF risk increased by 17% among those who experienced tinnitus occasionally (1.17; 1.09-1.25), 23% among those who experienced tinnitus frequently (1.23; 1.10-1.39), and 32% among those who experienced tinnitus consistently (1.32; 1.22-1.42). No significant difference was observed across different groups of genetic risk score for AF onset. CONCLUSIONS: Our study provides evidence regarding significant associations of hearing difficulty, use of hearing aid, and tinnitus with risk of incident AF. Findings highlight the potential that screening hearing disorders can benefit AF prevention.

Association of plant-based diets with total and cause-specific mortality across socioeconomic deprivation level: a large prospective cohort.

PURPOSE: Current evidence on the association between plant-based diet indices (PDIs) and mortality is inconsistent. We aimed to investigate the association of PDIs with all-cause and cause-specific mortality and to examine whether such associations were modified by socioeconomic deprivation level. METHODS: A total of 189,003 UK Biobank participants with at least one 24-h dietary assessment were included. All food items were categorised into three groups, including healthy plant foods, less healthy plant foods, and animal foods. Three PDIs, including the overall PDI (positive scores for all plant-based food intake and inverse scores for animal-based foods), the healthful PDI (hPDI) (positive scores only for healthy plant food intake and inverse scores for others), and the unhealthful PDI (uPDI) (positive scores only for less healthy plant food intake and inverse scores for others), were calculated according to the quantities of each food subgroup in three categories. The Townsend deprivation index was used as the indicator of socioeconomic deprivation level. Cox proportional hazard models were used to estimate the hazard ratios (HRs) of PDIs for all-cause and cause-specific mortality. The modification effects of socioeconomic deprivation levels on these associations were evaluated. RESULTS: During a median follow-up of 9.6 years, 9335 deaths were documented. Compared with the lowest quintile, the highest quintile of overall PDI was associated with adjusted HRs of 0.87 (95% CI 0.81-0.93) for all-cause mortality and 0.77 (0.66-0.91) for cardiovascular mortality. Compared with the lowest quintile, the highest quintile of hPDI was associated with lower risks of all-cause mortality (0.92, 0.86-0.98), and death caused by respiratory disease (0.63, 0.47-0.86), neurological disease (0.65, 0.48-0.88), and cancer (0.90, 0.82-0.99). Compared with the lowest quintile, the highest quintile of uPDI was associated with an HR of 1.29 (1.20-1.38) for all-cause mortality, 1.95 (1.40-2.73) for neurological mortality, 1.54 (1.13-2.09) for respiratory mortality, and 1.16 (1.06-1.27) for cancer mortality. The magnitudes of associations of hPDI and uPDI with mortality were larger in the most socioeconomically deprived participants (the highest tertile) than in the less deprived ones (p-values for interaction were 0.039 and 0.001, respectively). CONCLUSIONS: This study showed that having a high overall PDI and hPDI were related to a reduced risk of death, while the uPDI was linked to a higher risk of death. Sticking to a healthy plant-based diet may help decrease mortality risks across socioeconomic deprivation levels, especially for those who are the most socioeconomically deprived.

Associations of sugar-sweetened, artificially sweetened, and naturally sweet juices with Alzheimer's disease: a prospective cohort study.

Epidemiological studies of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) with Alzheimer's disease (AD) have provided controversial findings. Furthermore, little is known about the association between pure fruit/vegetable juices and AD. The present study aims to estimate the associations of SSBs, ASBs, and pure fruit/vegetable juices with AD, and to evaluate the theoretical effects of replacing SSBs and ASBs with the different consumption of pure fruit/vegetable juices on the risk of AD. This prospective cohort study of the UK Biobank included 206,606 participants aged 39-72 years free of dementia at baseline between 2006 and 2010. Dietary intake of SSBs, ASBs, and pure fruit/vegetable juices (naturally sweet juices) were collected using a 24-h dietary recall questionnaire completed between 2009 and 2012. Incident AD was identified by medical and mortality records. Cox proportional hazard models and substitution models were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 699 cases of AD were identified over a median follow-up of 9.5 years. The consumption of SSBs and ASBs (> 2 units/d) were associated with a higher risk of AD. However, participants who drank > 1-2 units/d of pure fruit/vegetable juices were associated with a lower risk of AD. In substitution models, replacing SSBs with an equivalent consumption of pure fruit/vegetable juices could be associated with a risk reduction of AD.

Predictive value of lung function measures for cardiovascular risk: a large prospective cohort study.

INTRODUCTION: Although lung function measures are associated with cardiovascular disease (CVD), the added predictive values of these measures remain unclear. METHODS: From the UK Biobank, 308 415 participants free of CVD with spirometry parameters were included. The CVD outcomes included were defined by QRISK3, the American College of Cardiology/American Heart Association (ACC/AHA) and the European Systematic Coronary Risk Evaluation (SCORE) prediction models, respectively. Cox proportional hazard models were used to estimate the associations of lung function measures with CVD outcomes. The predictive capability was determined by the decision curve analyses. RESULTS: Over a median follow-up of 12.5 years, 21 885 QRISK3 events, 12 843 ACC/AHA events and 2987 SCORE events were recorded. The associations of spirometry parameters with CVD outcomes were L-shaped. Restrictive and obstructive impairments were associated with adjusted HRs of 1.84 (95% CI: 1.65 to 2.06) and 1.72 (95% CI: 1.55 to 1.90) for SCORE CVD, respectively, compared with normal spirometry. Similar associations were seen for QRISK3 CVD (restrictive vs normal, adjusted HR: 1.30, 95% CI: 1.25 to 1.36; obstructive vs normal, adjusted HR: 1.20, 95% CI: 1.15 to 1.25) and ACC/AHA CVD (restrictive vs normal, adjusted HR: 1.39, 95% CI: 1.31 to 1.47; obstructive vs normal, adjusted HR: 1.26, 95% CI: 1.19 to 1.33). Using models that integrated non-linear forced expiratory volume in 1 s led to additional 10-year net benefits per 100 000 persons of 25, 43 and 5 for QRISK3 CVD at the threshold of 10%, ACC/AHA CVD at 7.5% and SCORE CVD at 5.0%, respectively. CONCLUSION: Clinicians could consider spirometry indicators in CVD risk assessment. Cost-effectiveness studies and clinical trials are needed to put new CVD risk assessment into practice.

A low-inflammatory diet is associated with a lower incidence of diabetes: role of diabetes-related genetic risk.

BACKGROUND: Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes. METHODS: Among 142,271 diabetes-free UK Biobank participants (aged 39-72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7-6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression. RESULTS: During follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group. CONCLUSIONS: A low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.

Radiomic texture analysis based on neurite orientation dispersion and density imaging to differentiate glioblastoma from solitary brain metastasis.

BACKGROUND: We created discriminative models of different regions of interest (ROIs) using radiomic texture features of neurite orientation dispersion and density imaging (NODDI) and evaluated the feasibility of each model in differentiating glioblastoma multiforme (GBM) from solitary brain metastasis (SBM). METHODS: We conducted a retrospective study of 204 patients with GBM (n = 146) or SBM (n = 58). Radiomic texture features were extracted from five ROIs based on three metric maps (intracellular volume fraction, orientation dispersion index, and isotropic volume fraction of NODDI), including necrosis, solid tumors, peritumoral edema, tumor bulk volume (TBV), and abnormal bulk volume. Four feature selection methods and eight classifiers were used for the radiomic texture feature selection and model construction. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the models. Routine magnetic resonance imaging (MRI) radiomic texture feature models generated in the same manner were used for the horizontal comparison. RESULTS: NODDI-radiomic texture analysis based on TBV subregions exhibited the highest accuracy (although nonsignificant) in differentiating GBM from SBM, with area under the ROC curve (AUC) values of 0.918 and 0.882 in the training and test datasets, respectively, compared to necrosis (AUCtraining:0.845, AUCtest:0.714), solid tumor (AUCtraining:0.852, AUCtest:0.821), peritumoral edema (AUCtraining:0.817, AUCtest:0.762), and ABV (AUCtraining:0.834, AUCtest:0.779). The performance of the five ROI radiomic texture models in routine MRI was inferior to that of the NODDI-radiomic texture model. CONCLUSION: Preoperative NODDI-radiomic texture analysis based on TBV subregions shows great potential for distinguishing GBM from SBM.

Unraveling the causal genes and transcriptomic determinants of human telomere length.

Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.

Circulating insulin-like growth factor-1 and brain health: Evidence from 369,711 participants in the UK Biobank.

BACKGROUND: The effects of insulin-like growth factor-1 (IGF-1) deficiency on cognitive decline have been consistently reported in animal studies, but the relationship between IGF-1 and human brain health remains controversial. Our study aimed to investigate the associations of serum IGF-1 concentrations with some brain-related disorders and neuroimaging features. METHODS: This prospective study included 369,711 participants (55.8 ± 8.1 years) from the UK biobank who had serum IGF-1 measured and were free from brain-related disorders of interest - dementia, stroke, and Parkinson's disease (PD) - at enrollment (2006-2010). Restricted cubic splines and Cox proportional hazards models were used to detect the associations between IGF-1 concentrations and brain-related diseases. In addition, general linear regressions were applied to explore the relationship between IGF-1 concentrations and neuroimaging features (volumes of white matter, grey matter, and hippocampus and white matter hyperintensity) among a sub-sample of 36,458 participants with magnetic resonance imaging data collected since 2014. RESULTS: During a median follow-up of 12.6 years, a total of 4,857 dementia, 6,240 stroke, and 2,116 PD cases were documented. The dose-response analyses yielded U-shaped relationships between IGF-1 concentrations and risks of dementia and stroke (P < 0.001 for non-linearity), with the lowest risks at 18 nmol/L and 26 nmol/L, respectively. A positive linear relationship was observed between IGF-1 concentrations and risk of PD (P = 0.163 for non-linearity). Moreover, neuroimaging analyses showed that higher IGF-1 concentrations were associated with greater volumes of white matter (ß = 2.98 × 10-4, P < 0.001) and hippocampus (ß = 3.37 × 10-4, P = 0.002) and smaller white matter hyperintensity (ß = -3.12 × 10-3, P < 0.001). CONCLUSIONS: Apart from the diverse associations with neuroimaging features, both low and high IGF-1 concentrations are associated with increased risks of dementia and stroke and higher IGF-1 concentrations are linked to a higher risk of PD, highlighting the potential of IGF-1 as a biomarker for risk stratification of brain health.

The associations of dietary patterns with depressive and anxiety symptoms: a prospective study.

BACKGROUND: Diet is increasingly recognized as an important risk factor for mental health. However, evidence regarding the association between diet pattern and depressive and anxiety symptoms is limited. We aimed to investigate the associations of dietary patterns characterized by a set of nutrients of interest with depressive and anxiety symptoms. METHODS: The analyses included a total of 126,819 participants in the UK Biobank who had completed at least two dietary questionnaires. Dietary data were obtained through 24-h dietary assessment at baseline between 2006 and 2010 and four rounds of online follow-ups between 2011 and 2012. Reduced rank regression was applied to derive dietary patterns (DPs) explaining variability in energy density, free sugars, saturated fat, and fiber intakes. Depressive and anxiety symptoms were measured by the Patient Health Questionnaire-9 and General Anxiety Disorder-7 between 2016 and 2017, respectively. Logistic regression models were performed to investigate the associations between dietary patterns and depressive and anxiety symptoms. RESULTS: During a mean follow-up of 7.6 years, 2746 cases of depressive symptoms and 2202 cases of anxiety symptoms were recorded. Three major DPs were derived, explaining 74% of the variation in nutrients hypothesized to be related to depressive and anxiety symptoms. DP1 was characterized by high intakes of chocolate, confectionery, butter, and low vegetable/fruit intakes. Compared to the lowest quintile of DP1, the odds ratio (95% confidence interval) of depressive symptoms for Q2-Q5 was 0.82 (0.72-0.93), 0.86 (0.76-0.98), 1.02 (0.90-1.15), and 1.17 (1.03-1.32), respectively. Compared to the lowest quintile of DP1, the odds ratio (95% CI) of anxiety symptoms for Q2-Q5 was 0.84 (0.73-0.97), 0.91 (0.79-1.05), 1.01 (0.88-1.15), and 1.18 (1.03-1.35), respectively. DP2 featured high intakes of sugar-sweetened beverages, added sugars, and low intakes of butter/cheese but showed no significant links to depressive or anxiety symptoms. DP3 was characterized by high butter and milk desserts and low alcohol/bread intakes. Compared to the lowest quintile of DP3, the odds ratio (95% CI) of depressive symptoms for Q2-Q5 was 0.90 (0.79-1.01), 1.00 (0.88-1.13), 1.06 (0.94-1.20), and 1.17 (1.03-1.32), respectively. Compared to the lowest quintile of DP3, the odds ratio (95% CI) of anxiety symptoms for Q2-Q5 was 0.90 (0.78-1.04), 1.05 (0.91-1.20), 1.02 (0.89-1.17), and 1.21 (1.05-1.38), respectively. CONCLUSIONS: A DP characterized by high intakes of chocolate and confectionery, butter, high-fat cheese, added sugars, along with low intakes of fresh fruit and vegetables, is associated with a higher risk of depressive and anxiety symptoms.

Associations between an obesity-related dietary pattern and incidence of overall and site-specific cancers: a prospective cohort study.

BACKGROUND: A dietary pattern (DP) may impact on cancer incidence more strongly than individual foods, but this association remains uncertain. Here, we aimed to broadly explore the associations of an obesity-related DP with overall and 19 site-specific cancers. METHODS: This study included 114,289 cancer-free participants with at least two dietary assessments. A total of 210 food items were classified into 47 food groups, and the mean amount of each food group was used in reduced-rank regression to derive the obesity-related DP. Cox regressions were conducted to explore the associations of the obesity-related DP with overall and 19 site-specific cancers. The parallel mediation model was constructed to quantify the mediating roles of potential mediators. RESULTS: During a median follow-up period of 9.4 years, 10,145 (8.9%) incident cancer cases were documented. The derived-DP was characterized by a higher intake of beer and cider, processed meat, high sugar beverages, red meat, and artificial sweetener, and a lower intake of fresh vegetables, olive oil, tea, and high fiber breakfast cereals. Observational analysis showed that a higher obesity-related DP Z-score was linearly associated with an increased risk of overall cancer (adjusted hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.04 per 1-SD increase, corrected P < 0.001). For site-specific cancer, positive linear associations for six cancer sites (oral, colorectal, liver, lung, endometrium, and thyroid) and nonlinear associations for six cancer sites (esophagus, malignant melanoma, prostate, kidney, bladder, and multiple myeloma) were observed. The paralleled mediation analysis suggested that the association between the obesity-related DP and overall cancer is mediated by the body mass index (BMI), the waist-to-hip ratio (WHR), C-reactive protein, high-density lipoproteins (HDLs), and triglycerides. CONCLUSIONS: The developed obesity-related DP is strongly associated with overall and multiple cancer sites. Our findings highlight the complicated and diverse associations between an obesity-related DP and cancers and provide clues for future research directions.

Healthy sleep patterns and common mental disorders among individuals with cardiovascular disease: A prospective cohort study.

BACKGROUND: Sleep behaviors are potentially modifiable risk factors for common mental disorders and cardiovascular disease (CVD). However, the associations between combined sleep behaviors and common mental disorders among individuals with CVD remain unclear. METHODS: A total of 18,776 participants with a history of CVD from UK Biobank, who were free of depression or anxiety from 2006 to 2010 were included. A composite healthy sleep score was constructed based on five sleep behaviors (chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness). Cox proportional hazard regression models were performed to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for incident depression and anxiety. RESULTS: During a median follow-up of 11.8 years, 965 depression and 812 anxiety cases were recorded. The adjusted HRs for participants with a healthy sleep pattern compared with a poor sleep pattern were 0.45 (95 % CI: 0.35-0.57) for depression and 0.77 (95 % CI: 0.58-1.03) for anxiety. There was a linear dose-response association of healthy sleep score with incident depression and anxiety (HR = 0.82, 95 % CI: 0.77-0.87; HR = 0.92, 95 % CI: 0.86-0.99 per 1-score increase, respectively). Likewise, these associations were observed among individuals with coronary heart disease, stroke, heart failure and atrial fibrillation. CONCLUSIONS: A healthy sleep pattern is significantly associated with a lower risk of depression among individuals with CVD, highlighting the importance of monitoring and improving sleep health in the prevention of common mental disorders among individuals with CVD.