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Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n  = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of −50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes. [ABSTRACT FROM AUTHOR]

Current understanding of determinants for COVID-19-related cardiovascular and thromboembolic (CVE) complications primarily covers clinical aspects with limited knowledge on genetics and lifestyles. Here, we analysed a prospective cohort of 106,005 participants from UK Biobank with confirmed SARS-CoV-2 infection. We show that higher polygenic risk scores, indicating individual's hereditary risk, were linearly associated with increased risks of post-COVID-19 atrial fibrillation (adjusted HR 1.52 [95% CI 1.44 to 1.60] per standard deviation increase), coronary artery disease (1.57 [1.46 to 1.69]), venous thromboembolism (1.33 [1.18 to 1.50]), and ischaemic stroke (1.27 [1.05 to 1.55]). These genetic associations are robust across genders, key clinical subgroups, and during Omicron waves. However, a prior composite healthier lifestyle was consistently associated with a reduction in all outcomes. Our findings highlight that host genetics and lifestyle independently affect the occurrence of CVE complications in the acute infection phrase, which can guide tailored management of COVID-19 patients and inform population lifestyle interventions to offset the elevated cardiovascular burden post-pandemic. Cardiovascular and thromboembolic events (CVE) are common among hospitalised COVID-19 patients and are causes of many COVID-19-related deaths. Here, the authors examine whether genetic predisposition and lifestyle factors are associated with the risk of post-COVID-19 CVE using data from UK Biobank. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have not found a conclusive association between serum 25‐hydroxyvitamin D (25(OH)D) levels and allergic rhinitis (AR) or allergic sensitization (AS). Objective: To investigate a causal association between 25(OH)D levels with risk of AR and AS, using a two‐sample Mendelian randomization (MR) approach. Methods: Seven single nucleotide polymorphisms (SNPs), previously shown to be associated with serum 25(OH)D levels, were identified as instrumental variables. The primary outcome was AR, and the secondary outcomes were AS and non‐allergic rhinitis (NAR). The genome‐wide association (GWA) summary statistics of the outcomes were obtained from two cohort studies (EAGLE Consortium and UK Biobank). An MR analysis with random‐effects inverse‐variance weighted method was performed as the primary analysis to estimate overall effect size (odds ratio [OR] and 95% confidence interval [CI]). Sensitivity analysis using weighted median method and MR‐Egger regression method was conducted. A subgroup analysis based on 25(OH)D synthesis‐related SNPs was further applied. Results: Serum 25(OH)D levels were not causally associated with risk of AR (OR: 0.960; 95% CI: 0.779‐1.184), AS (OR: 1.059; 95% CI: 0.686 to 1.634) or NAR (OR: 0.937; 95% CI: 0.588‐1.491). Subgroup analysis also showed null association between 25(OH)D synthesis‐related SNPs and the outcomes. Sensitivity analyses yielded similar results. Conclusions and Clinical Relevance: This MR study found no evidence supporting a causal association between serum 25(OH)D levels and risk of AR, AS and NAR in European‐ancestry population. This argues against the previous postulation that vitamin D supplementation is effective in prevention of allergic diseases. [ABSTRACT FROM AUTHOR]

Background: The independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain., Objectives: This study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD., Methods: This prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR., Results: In total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS., Conclusions: WHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR., Competing Interests: Conflict of interest MW does consultancy for Amgen and Freeline outside the submitted work; no support from any organization for the submitted work; no other relationships or activities that could appear to have influenced the submitted work. All other authors report no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear., Methods: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources., Results: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g., Limitations: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples., Conclusions: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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).)

UK Biobank is a large-scale prospective study with deep phenotyping and genomic data. Its open-access policy allows researchers worldwide, from academia or industry, to perform health research in the public interest. Between 2006 and 2010, the study recruited 502,000 adults aged 40-69 years from the general population of the United Kingdom. At enrolment, participants provided information on a wide range of factors, physical measurements were taken, and biological samples (blood, urine and saliva) were collected for long-term storage. Participants have now been followed up for over a decade with more than 52,000 incident cancer cases recorded. The study continues to be enhanced with repeat assessments, web-based questionnaires, multi-modal imaging, and conversion of the stored biological samples to genomic and other '-omic' data. The study has already demonstrated its value in enabling research into the determinants of cancer, and future planned enhancements will make the resource even more valuable to cancer researchers. Over 26,000 researchers worldwide are currently using the data, performing a wide range of cancer research. UK Biobank is uniquely placed to transform our understanding of the causes of cancer development and progression, and drive improvements in cancer treatment and prevention over the coming decades., (© 2022. The Author(s).)

Long-term blood pressure variability (BPV) is a risk factor for cardiovascular diseases, dementia, and stroke. However, its genetic architecture is not fully understood. This study aims to explore its genetic factors and provide more evidence on the mechanisms and further pathological study of BPV. The genome-wide association study (GWAS) is based on the UK Biobank cohort. There were four data collection rounds from 2006 to 2020, and 9370 participants with more than three blood pressure measurements were included. They had a median age of 55 and a male percentage of 50.1%. The phenotypes (BPV) were calculated by four methods and the genetic data contains 6 884 260 single nucleotide polymorphisms (SNPs) after imputation and quality control. A linear regression model was performed with adjustments for sex, age, genotype array, and a significant principal component. Subgroup analysis was performed on hypertension-free participants. The significant and suggestive significant P thresholds were set as 5 × 10 -8 and 1 × 10 -6 . Six genetic loci (BAD, CCDC88B, GPR137, PLCB3, RPS6KA4 for systolic BPV, and WWC2 for diastolic BPV) were identified by coding region SNPs at the suggestive significant P threshold (1 × 10 -6 ). Among them, gene CCDC88B and RPS6KA4 reached the significant P threshold (5 × 10 -8 ), with the strongest signal of SNP rs1229536170 (P = 6.36 × 10 -8 , β = -.29). The annotation results indicate that genes CCDC88B, GPR137, RPS6KA4, and BAD are associated with long-term SBPV. Their functions of inflammation, epithelial dysfunction, and apoptosis are related to artery stiffness, which was reported as potential mechanisms of BPV., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

UK Biobank is an intensively characterized prospective study of 500 000 men and women, aged 40 to 69 years when recruited, between 2006 and 2010, from the general population of the United Kingdom. Established as an open-access resource for researchers worldwide to perform health research that is in the public interest, UK Biobank has collected (and continues to collect) a vast amount of data on genetic, physiological, lifestyle, and environmental factors, with prolonged follow-up of heath conditions through linkage to administrative electronic health records. The study has already demonstrated its unique value in enabling research into the determinants of common endocrine and metabolic diseases. The importance of UK Biobank, heralded as a flagship project for UK health research, will only increase over time as the number of incident disease events accrue, and the study is enhanced with additional data from blood assays (such as whole-genome sequencing, metabolomics, and proteomics), wearable technologies (including physical activity and cardiac monitors), and body imaging (magnetic resonance imaging and dual-energy X-ray absorptiometry). This unique research resource is likely to transform our understanding of the causes, diagnosis, and treatment of many endocrine and metabolic disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background & Aims: Processed meat and high sodium intake are common in Western diet. The objective was to examine their independent effects on the risk of colorectal cancer (CRC)., Methods: We performed both observational analysis with UK Biobank and genetic analysis with Mendelian randomization (MR). The 24-h urinary sodium (UNa) and reported intake of processed meat were fitted on incident CRC by multivariable Cox proportional hazard model, adjusted for covariates, such as age, gender, family history, etc. Different sodium measures were used for sensitivity analyses. Two-sample MR analyses were performed using summary data from genome-wide association studies of UNa and CRC. Multivariable MR was adjusted for body mass index., Results: We included 415 524 eligible participants from UK Biobank. During a median follow-up of 11.1 years, 2663 participants were diagnosed with CRC. High intake of processed meat independently increased risk of CRC by 23% (HR 1.23; 95% CI: 1.03 to 1.46), but 24-h UNa was not significantly associated with CRC (HR 0.96; 95% CI: 0.87 to 1.06). Furthermore, MR also showed little evidence for the effect of UNa on CRC (OR 1.02; 95% CI: 0.11 to 9.42). Sensitivity analyses showed consistent results across different measurements of sodium intake., Conclusions: Intake of processed meat had an independent effect on the risk of CRC, but the risk was not associated with sodium level. Reduction of processed meat intake may be an effective strategy for CRC prevention, while sodium reduction should still be recommended to achieve other health benefits., Competing Interests: Conflict of Interest None to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)