UK Biobank Study Research Articles

Using Artificial Intelligence to Predict Heart Failure Risk from Single-lead Electrocardiographic Signals: A Multinational Assessment.

Despite the availability of disease-modifying therapies, scalable strategies for heart failure (HF) risk stratification remain elusive. Portable devices capable of recording single-lead electrocardiograms (ECGs) can enable large-scale community-based risk assessment. To evaluate an artificial intelligence (AI) algorithm to predict HF risk from noisy single-lead ECGs. Multicohort study. Retrospective cohort of individuals with outpatient ECGs in the integrated Yale New Haven Health System (YNHHS) and prospective population-based cohorts of UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Individuals without HF at baseline. AI-ECG-defined risk of left ventricular systolic dysfunction (LVSD). Among individuals with ECGs, we isolated lead I ECGs and deployed a noise-adapted AI-ECG model trained to identify LVSD. We evaluated the association of the model probability with new-onset HF, defined as the first HF hospitalization. We compared the discrimination of AI-ECG against the pooled cohort equations to prevent HF (PCP-HF) score for new-onset HF using Harrel's C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). There were 194,340 YNHHS patients (age 56 years [IQR, 41-69], 112,082 women [58%]), 42,741 UKB participants (65 years [59-71], 21,795 women [52%]), and 13,454 ELSA-Brasil participants (56 years [41-69], 7,348 women [55%]) with baseline ECGs. A total of 3,929 developed HF in YNHHS over 4.5 years (2.6-6.6), 46 in UKB over 3.1 years (2.1-4.5), and 31 in ELSA-Brasil over 4.2 years (3.7-4.5). A positive AI-ECG screen was associated with a 3- to 7-fold higher risk for HF, and each 0.1 increment in the model probability portended a 27-65% higher hazard across cohorts, independent of age, sex, comorbidities, and competing risk of death. AI-ECG's discrimination for new-onset HF was 0.725 in YNHHS, 0.792 in UKB, and 0.833 in ELSA-Brasil. Across cohorts, incorporating AI-ECG predictions in addition to PCP-HF resulted in improved Harrel's C-statistic (Δ=0.112-0.114), with an IDI of 0.078-0.238 and an NRI of 20.1%-48.8% for AI-ECG vs. PCP-HF. Across multinational cohorts, a noise-adapted AI model with lead I ECGs as the sole input defined HF risk, representing a scalable portable and wearable device-based HF risk-stratification strategy.

#1054 Dietary manganese intake and risk of chronic kidney disease: insights from the UK Biobank Study

Abstract Background and Aims Manganese, an essential trace element crucial for various physiological processes, has been linked to metabolic syndrome and cardiovascular health. Despite these associations, the relationship between dietary manganese intake and incident chronic kidney disease (CKD) remains unclear. In this study, the connection between dietary manganese consumption and the development of CKD in individuals with normal kidney function was investigated. Method A total of 135,577 participants enrolled in the UK Biobank were assessed. Dietary manganese intake was determined through a 24-hour dietary recall questionnaire and categorized into quartiles. Individuals with prevalent CKD or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline were excluded. The primary outcome was incident CKD diagnosed using ICD-10 and OPCS-4 codes. Incident CKD, defined as eGFR <60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, was also evaluated in a sub-cohort that included eGFR and UACR follow-up data. Results During a follow-up period of 1,492,228 person-years (median, 11.2 years), incident CKD occurred in 4,900 (3.6%) participants. The incidence of CKD exhibited a progressive increase among individuals with low manganese intake (2.3, 3.0, 3.6, and 4.2 events per 1000 person-years in Q4–Q1, respectively). In a multivariate Cox proportional hazard model, the adjusted hazard ratios (95% confidence intervals) for the lowest, second, and third quartiles were 1.39 (1.26–1.54), 1.22 (1.11–1.34), and 1.12 (1.02–1.23), respectively, compared to the highest quartile. Similar findings were observed in relation to eGFR or UACR-defined CKD outcomes. Conclusion Lower dietary manganese consumption was found to be associated with an elevated risk of incident CKD in adults with normal kidney function. This implies that a deficiency in dietary manganese intake may contribute to an increased risk of CKD development.

Risk/benefit trade-off of habitual physical activity and air pollution on mortality: A large-scale prospective analysis in the UK Biobank

BackgroundPrevious observational studies have indicated associations of physical activity (PA) and air pollution with mortality. A few studies have evaluated air pollution and PA interactions for health. Still, the trade-off between the harmful effects of air pollution exposure and the protective effects of PA remains controversial and unclear. ObjectiveThis study aimed to investigate the joint association of air pollution and PA with mortality risks. MethodsThis prospective cohort study included 322,092 participants from 2006 to 2010 and followed up to 2021 in the UK Biobank study. The concentrations of air pollutants (2006–2010), including particulate matter (PM) with diameters <=2.5 mm (PM2.5), <=10 mm (PM10), and between 2.5 and 10 mm (PM2.5–10), and nitrogen oxides (NO2 and NOx) were obtained. Information on PA measured by the International Physical Activity Questionnaire short form (2006–2010) and wrist-worn accelerometer (2013–2015) were collected. All-cause and cause-specific mortalities were recorded. Cox proportional hazard models were used to investigate the associations of air pollution exposure and PA with mortality risks. The additive and multiplicative interactions were also examined. ResultsDuring a mean follow-up of 11.83 years, 16629 deaths were recorded. Compared with participants reporting low PA, higher PA was negatively associated with all-cause [hazard ratio (HR), 0.74; 95% CI, 0.71–0.78], cancer (HR, 0.85; 95% CI, 0.80–0.90), CVD (HR, 0.79; 95% CI, 0.71–0.87), and respiratory disease-specific mortality (HR, 0.51; 95% CI, 0.44–0.60). Exposure to PM2.5 (HR, 1.05; 95% CI, 1.00–1.09) and NOx (HR, 1.06; 95% CI, 1.02–1.10) was connected with increased all-cause mortality risk, and significant PM2.5-associated elevated risks for CVD mortality and NOx-associated elevated risks for respiratory disease mortality were observed. No obvious interaction between PA and PM2.5 or NOx exposure was detected. ConclusionsOur study provides additional evidence that higher PA and lower air pollutant levels are independently connected with reduced mortality risk. The benefits of PA are not significantly affected by long-term air pollution exposure, indicating PA can be recommended to prevent mortality regardless of air pollution levels. Our findings highlight the importance of public health policies and interventions facilitating PA and reducing air pollution in reducing mortality risks and maximizing health benefits. Future investigation is urgently needed to identify these findings in areas with severe air pollution conditions.

The associations of social health, self-injurious thoughts and behaviors with or without childhood trauma: A UK biobank study

BackgroundChildhood trauma was known to increase risks of social isolation, loneliness and self-injurious thoughts and behaviors in adulthood. The aim of this study was to examine the protect and risk factors of social health, self-injurious thoughts and behaviors between adults with or without childhood trauma. MethodThis was a cross-sectional study comprising of 145,043 participants enrolled in the UK Biobank. Childhood trauma was determined by the Childhood Trauma Screener. Social health included social isolation, loneliness and emotional support. Outcomes of self-injurious thoughts and behaviors included suicide ideation, suicide attempt and non-suicidal self-injury (NSSI). Demographic data, self-reported morbidities and other confounding variables were covariates. Stata 17.0 and SPSS 27.0 was used to analysis data. ResultsCompared with participants without childhood trauma, there was no protective effect of emotional support for NSSI in participants with childhood trauma (β-value difference = 0.334, p = 0.008). The risk effect of loneliness for suicide ideation, suicide attempt and NSSI were also weaker in participants experiencing childhood trauma (p<0.05). Social isolation was no longer a risk factor for NSSI in all participants, while loneliness remained as a threat (p < 0.05). LimitationsMany variables were measured using core items of the scale in UK Biobank, meanwhile, the childhood trauma data collected in adulthood may have recall bias. ConclusionsAdults reported childhood trauma were less vulnerable to self-injurious thoughts and behaviors when experiencing loneliness, but they could also not be protected from NSSI through emotional support. Emotional dysregulation caused by childhood trauma may contribute to this.

Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study.

The purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR). Single nucleotide polymorphism-based genome-wide association analyses of statins were collected from the UK Biobank and FinnGen dataset, and OA data were collected from the UK Biobank and Arthritis Research UK Osteoarthritis Genetics (arcOGEN) study. Two-sample MR analyses were performed using the inverse-variance weighted (IVW) technique. MR-Egger, weighted median, and weighted mode served as supplementary analyses. MR-Egger regression, Cochran's Q test, and Mendelian Randomization Pleiotropy Residual Sum and Outlier analysis were performed as sensitivity analyses. Hydroxymethylglutaryl-coenzyme A reductase (HMGCR) expression and OA risk were evaluated using summary data-based MR (SMR). MR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: β = -2.989, P = 0.003) and rosuvastatin (IVW: β = -14.141, P = 0.006) treatment on hip OA. Meta-analysis showed the association between atorvastatin and knee OA was statistically significant (odds ratio 0.15; P = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: β = -1.056, P = 0.004) and hip OA (IVW: β = -1.405, P = 0.001). Statin medication showed a protective effect on hip OA (IVW: β = -0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (β = -0.193, PSMR = 0.017), rather than hip OA (β = 0.067, PSMR = 0.502), which suggested that statins' protective effect on OA may not be related to its lipid-lowering effect. This MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism.

The association between being breastfed in infancy and risks of cancer in adulthood—a UK Biobank study

BackgroundBeing breastfed has established benefits for infant health, but its long-term effects on adult diseases, including cancer, remain underexplored. We examined associations between being breastfed in infancy and the risks of common cancers.MethodsData from 339,115 participants (191,117 women) enrolled in the UK Biobank with self-reported breastfeeding data were linked to national cancer registries. Cox models estimated sex-specific hazard ratios (HR) and 95% confidence intervals (CI) for the associations between being breastfed (ever/never) and risks of overall cancer as well as common cancer sites.ResultsIn total, 34,392 incident cancers (17,895 in women) were registered. The HR of overall cancer associated with being breastfed was 1.05 (95% CI 1.01–1.09) in women and 1.00 (95% CI 0.96–1-04) in men. In site-specific analysis being breastfed was associated with an increased risk of breast and ovarian cancer in women and a reduced risk of oesophageal cancer in men.DiscussionWe found that having been breastfed was associated with a marginally increased risk of adult cancer in women, but we found no evidence of an association in men. These findings should be viewed within the study limitations, and do not outweigh the many benefits that breastfeeding provides.

Association between household size and risk of incident dementia in the UK Biobank study

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02–1.09), vascular dementia (HR, 1.08; 95% CI 1.01–1.15), and non-Alzheimer’s disease non-vascular dementia (HR, 1.09; 95% CI 1.03–1.14). No significant association was observed for Alzheimer’s disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer.

In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people's attention. Statin use may be potentially associated with a reduced risk of breast cancer. To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer. Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium's low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth. Data from about 3.8 million cancer patients and ~1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction (P=0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8+ T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy. The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8+ T-cell activity and leads to better prognostic characteristics.

A gap analysis of UK biobank publications reveals SNPs associated with intrinsic subtypes of breast cancer

Breast cancer is a multifaceted disease and a leading cause of cancer morbidity and mortality in females across the globe. In 2020 alone, 2.3 million women were diagnosed and 685,000 died of breast cancer worldwide. With the number of diagnoses projected to increase to 3 million per year by 2040 it is essential that new methods of detection and disease stratification are sought to decrease this global cancer burden.Although significant improvements have been made in breast cancer diagnosis and treatment, the prognosis of breast cancer remains poor in some patient groups (i.e. triple negative breast cancer), necessitating research into better patient stratification, diagnosis and drug discovery. The UK Biobank, a comprehensive biomedical and epidemiological database with a wide variety of multiomics data (genomics, proteomics, metabolomics) offers huge potential to uncover groundbreaking discoveries in breast cancer research leading to improved patient stratification. Combining genomic, proteomic, and metabolic profiles of breast cancer in combination with histological classification, can aid treatment decisions through accurate diagnosis and prognosis prediction of tumor behaviour.Here, we systematically reviewed PubMed publications reporting the analysis of UK Biobank data in breast cancer research. Our analysis of UK Biobank studies in the past five years identified 125 publications, of which 76 focussed on genomic data analysis. Interestingly, only two studies reported the analysis of metabolomics and proteomics data, with none performing multiomics analysis of breast cancer. A meta-analysis of the 76 publications identified 2870 genetic variants associated with breast cancer across 445 genes. Subtype analysis revealed differential genetic alteration in 13 of the 445 genes and the identification of 59 well-established breast cancer genes. in differential pathways. Pathway interaction analyses illuminated their involvement in general cancer biomolecular pathways (e.g. DNA damage repair, Gene expression). While our meta-analysis only measured genetic differences in breast cancer due to current usage of UK Biobank data, minimal multi-omics analyses have been performed and the potential for harnessing multi-omics strategies within the UK Biobank cohort holds promise for unravelling the biological signatures of distinct breast cancer subtypes further in the future.

Sleep Pattern, Genetic Susceptibility, and Abdominal Aortic Aneurysm in UK Biobank Participants: Large-Scale Cohort Study

BackgroundAbdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality. ObjectivesThe authors aimed to explore the associations between sleep patterns and genetic susceptibility to AAA. MethodsWe included 344,855 UK Biobank study participants free of AAA at baseline. A sleep pattern was defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness, and an overall sleep score was constructed with a range from 0 to 5, where a high score denotes a healthy sleep pattern. Polygenic risk score based on 22 single nucleotide polymorphisms was categorized into tertiles and used to evaluate the genetic risk for AAA. Cox proportional hazards regression models were used to assess the association between sleep, genetic factors, and the incidence of AAA. ResultsDuring a median of 12.59 years of follow-up, 1,622 incident AAA cases were identified. The HR per 1-point increase in the sleep score was 0.91 (95% CI: 0.86-0.96) for AAA. Unhealthy sleep patterns, defined as a sleep score ranging from 0 to 3, were found to be associated with a higher risk of AAA for the intermediate (HR: 1.18, 95% CI: 1.06-1.31) and poor sleep patterns (HR: 1.40, 95% CI: 1.13-1.73), respectively, compared to the healthy pattern. Participants with poor sleep patterns and high genetic risks had a 2.5-fold higher risk of AAA than those with healthy sleep patterns and low genetic risk. ConclusionsIn this large prospective study, healthy sleep patterns were associated with a lower risk of AAA among participants with low, intermediate, or high genetic risk.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P<0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P<0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P<0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P<0.001). Stronger associations with glaucoma (P interaction=0.001) were noted in participants with a higher glaucoma polygenic risk score. Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Determinants of plasma levels of proglucagon and the metabolic impact of glucagon receptor signalling: a UK Biobank study

Aims/hypothesesGlucagon and glucagon-like peptide-1 (GLP-1) are derived from the same precursor; proglucagon, and dual agonists of their receptors are currently being explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated levels of endogenous glucagon (hyperglucagonaemia) have been linked with hyperglycaemia in individuals with type 2 diabetes but are also observed in individuals with obesity and MASLD. GLP-1 levels have been reported to be largely unaffected or even reduced in similar conditions. We investigated potential determinants of plasma proglucagon and associations of glucagon receptor signalling with metabolic diseases based on data from the UK Biobank.MethodsWe used exome sequencing data from the UK Biobank for ~410,000 white participants to identify glucagon receptor variants and grouped them based on their known or predicted signalling. Data on plasma levels of proglucagon estimated using Olink technology were available for a subset of the cohort (~40,000). We determined associations of glucagon receptor variants and proglucagon with BMI, type 2 diabetes and liver fat (quantified by liver MRI) and performed survival analyses to investigate if elevated proglucagon predicts type 2 diabetes development.ResultsObesity, MASLD and type 2 diabetes were associated with elevated plasma levels of proglucagon independently of each other. Baseline proglucagon levels were associated with the risk of type 2 diabetes development over a 14 year follow-up period (HR 1.13; 95% CI 1.09, 1.17; n=1562; p=1.3×10−12). This association was of the same magnitude across strata of BMI. Carriers of glucagon receptor variants with reduced cAMP signalling had elevated levels of proglucagon (β 0.847; 95% CI 0.04, 1.66; n=17; p=0.04), and carriers of variants with a predicted frameshift mutation had higher levels of liver fat compared with the wild-type reference group (β 0.504; 95% CI 0.03, 0.98; n=11; p=0.04).Conclusions/interpretationOur findings support the suggestion that glucagon receptor signalling is involved in MASLD, that plasma levels of proglucagon are linked to the risk of type 2 diabetes development, and that proglucagon levels are influenced by genetic variation in the glucagon receptor, obesity, type 2 diabetes and MASLD. Determining the molecular signalling pathways downstream of glucagon receptor activation may guide the development of biased GLP-1/glucagon co-agonist with improved metabolic benefits.Data availabilityAll coding is available through https://github.com/nicwin98/UK-Biobank-GCGGraphical

Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study

BackgroundThe study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk. MethodsThe present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006–2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life’s Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into “mediation only” or pure indirect effect (PIE), “interaction only” or interaction referent (INTREF), “neither mediation nor interaction” or controlled direct effect (CDE), and “both mediation and interaction” or mediated interaction (INTMED). ResultsThe study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03–1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730). ConclusionDementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained ∼ 54 % of the total effect.

Metabolic Syndrome and the Risk of Kidney Stones: a Large-scale Cohort Study from 487,860 UK Biobank participants.

While some studies have suggested an association between metabolic syndrome and kidney stones, the quality and level of evidence in these studies vary. Whether some individual characteristics and clustering of metabolic syndrome traits increase the risk of kidney stones has not been examined in a large-scale prospective cohort. We conducted a retrospective analysis of data from a prospective cohort of 487,860 UK Biobank participants who were free from kidney stones at baseline. The presence of metabolic syndrome was based on five criteria: abdominal obesity, high triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, high blood pressure (HBP), and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to evaluate the association between metabolic syndrome and risk of kidney stones. After an average follow-up period of 12.6 years, a total of 5,213 of the 487,860 participants included in the UK Biobank study developed kidney stones. The partial traits of metabolic syndrome, including waist circumference (HR: 1.15, 95% CI: 1.10-1.20), HDL cholesterol (0.66, 0.55-0.79), HBP (1.11, 1.03-1.19) and T2DM (1.14, 1.04-1.21), were independently associated with the occurrence of kidney stones. The clustering of metabolic syndrome is significantly associated with kidney stone formation, and as the number of metabolic syndrome traits increases, the risk of kidney stones gradually increases. Metabolic syndrome is a significant and independent risk factor for the development of kidney stones. This association suggests that kidney stones may represent a systemic disorder influenced by the interplay of various metabolic risk factors.

Association of healthy diet score and adiposity with risk of colorectal cancer: findings from the UK Biobank prospective cohort study.

To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk.

Abstract 3091: Long-term Association Between Hip Or Knee Replacement Surgery And Venous Thromboembolism Risk: A Prospective Matched Cohort Study In The Uk Biobank

Background: Hip and knee replacement surgeries have been linked to a transient increase in venous thromboembolism (VTE) risk in the short term. However, there is limited evidence regarding the extended impact of these surgeries on VTE risk beyond the first year. Objective: This prospective matched cohort study aimed to investigate the associations between hip or knee replacement surgery and VTE risk over a 10-year period, examining how these associations evolved over time. Methods: Analyzing data from 496,862 adults recruited between 2006 and 2010 in the UK Biobank study, 21,155 hip replacement surgery patients and 21,899 knee replacement surgery patients were identified and matched with the general population using exposure density sampling. The piecewise Cox proportional hazards model was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for VTE outcomes at different intervals within the 10 years post-surgery. Results: For the hip replacement surgery cohort (n=221,138), the mean age was 61.5 (standard deviation [SD] 6.8), 40.7% were men, and 407 (1.9%) patients with hip surgery developed VTE during follow-up. In the knee replacement surgery cohort (n=199,487), the mean age was 61.7 (SD 6.4), 44.5% were men, and 436 (2.5%) patients with knee surgery developed VTE. Adjusting for various factors, the elevated risk peaked within 30 days post-surgery, with HRs (95% CIs) of 21.4 (15.4-29.6) and 33.0 (23.4-46.4) for hip and knee replacement, respectively. The elevated risk persisted until the tenth year, with HRs (95% CIs) of 1.59 (1.23-2.04) and 1.68 (1.21-2.33) for hip and knee replacement, respectively. These associations were held across participant characteristics and in sensitivity analysis. Conclusions: In middle-aged and older British adults, hip or knee replacement surgery was associated with both short- and long-term VTE risk, with the heightened risk persisting for up to a decade.

Relationships between orofacial pain and sleep: Analysis of UK biobank and genome-wide association studies data

Background/purposeOrofacial pain is common in dental practices. This study aimed to explore relationships between orofacial pain and sleep using the UK Biobank dataset and, based on epidemiological associations, to investigate the causal association using genome-wide association studies data. Materials and methodsFirst, a cross-sectional study was conducted with 196,490 participants from UK Biobank. Information on pain conditions and sleep traits was collected. Multivariable models were used to explore the relationships with odds ratio (OR). Second, Mendelian randomization analyses were conducted using data for orofacial pain, including temporomandibular joint disorders-related pain (n = 377,277) and atypical facial pain (n = 331,749), and sleep traits, including sleep duration (n = 446,118), short sleep (n = 411,934), long sleep (n = 339,926), snoring (n = 359,916), ease of getting up (n = 385,949), insomnia (n = 453,379), daytime dozing (n = 452,071), daytime napping (n = 452,633), and chronotype (n = 403,195). ResultsThe cross-sectional study confirmed the bidirectionality between pain and sleep. Participants experiencing pain all over the body showed a significant association with an unhealthy sleep pattern (OR = 1.18, P < 0.001) and other sleep traits (P < 0.05). Risks of chronic orofacial pain were associated with sleep duration in a non-linear relationship (P = 0.032). The Mendelian randomization analyses indicated that long sleep was causally associated with temporomandibular joint disorders-related pain (OR = 6.77, P = 0.006). ConclusionThe relationship between pain and sleep is bidirectional. Long sleep is found to be causally associated with chronic orofacial pain.

Sleep Patterns and Traditional Cardiovascular Health Metrics: Joint Impact on Major Adverse Cardiovascular Events in a Prospective Cohort Study.

This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns. We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow-up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257-0.365]; P<0.001). Elevated CVH scores were associated with a reduced risk of MACE across different sleep patterns. Similar trends were observed for individual MACE components, heart failure, and all-cause mortality. These findings remained robust in sensitivity analyses and across various subgroups. In individuals without known CVD, maintaining a favorable sleep pattern and achieving optimal CVH levels, as measured by traditional metrics, were associated with the lowest MACE risk. Enhanced CVH significantly reduced CVD risk, even in individuals with a poor sleep pattern. These results emphasize the importance of considering multiple dimensions of sleep health alongside CVH to mitigate CVD risk. URL: https://www.ukbiobank.ac.uk; Unique identifier: 91090.

Prevalence of Sarcopenia and Its Defining Components in Non-alcoholic Fatty Liver Disease Varies According to the Method of Assessment and Adjustment: Findings from the UK Biobank

Sarcopenia may increase non-alcoholic fatty liver disease (NAFLD) risk, but prevalence likely varies with different diagnostic criteria. This study examined the prevalence of sarcopenia and its defining components in adults with and without NAFLD and whether it varied by the method of muscle mass assessment [bioelectrical impedance (BIA) versus dual-energy X-ray absorptiometry (DXA)] and adjustment (height2 versus BMI). Adults (n = 7266) in the UK Biobank study (45–79 years) with and without NAFLD diagnosed by MRI, were included. Sarcopenia was defined by the 2018 European Working Group on Sarcopenia in Older People definition, with low appendicular skeletal muscle mass (ASM) assessed by BIA and DXA and adjusted for height2 or BMI. Overall, 21% of participants had NAFLD and the sex-specific prevalence of low muscle strength (3.6–7.2%) and sarcopenia (0.1–1.4%) did not differ by NAFLD status. However, NAFLD was associated with 74% (males) and 370% (females) higher prevalence of low ASM when adjusted for BMI but an 82% (males) to 89% (females) lower prevalence when adjusted for height2 (all P < 0.05). The prevalence of impaired physical function was 40% (males, P = 0.08) to 123% (females, P < 0.001) higher in NAFLD. In middle-aged and older adults, NAFLD was not associated with a higher prevalence of low muscle strength or sarcopenia but was associated with an increased risk of impaired physical function and low muscle mass when adjusted for BMI. These findings support the use of adiposity-based adjustments when assessing low muscle mass and the assessment of physical function in NAFLD.

Mendelian randomization study of whole blood viscosity and cardiovascular diseases.

Association between whole blood viscosity (WBV) and an increased risk of cardiovascular disease (CVD) has been reported. However, the causal relationship between WBV and CVD remains not thoroughly investigated. The aim of this study was to investigate the causal relation between WBV and CVD. Two-sample Mendelian randomization (MR) was employed, with inverse variance weighting (IVW) as the primary method, to investigate the casual relationship between WBV and CVD. The calculated WBV and medical records of 378,210 individuals participating in the UK Biobank study were divided into halves and analyzed. The means of calculated WBVs were 16.9 (standard deviation: 0.8) and 55.1 (standard deviation: 17.2) for high shear rate (HSR) and low shear rate (LSR), respectively. 37,859 (10.0%) major cardiovascular events (MACE) consisted of 23,894 (6.3%) cases of myocardial infarction (MI), 9,245 (2.4%) cases of ischemic stroke, 10,377 (2.7%) cases of revascularization, and 5,703 (1.5%) cases of coronary heart disease-related death. In the MR analysis, no evidence was found indicating a causal effect of WBV on MACE (IVW p-value for HSR = 0.81, IVW p-value for LSR = 0.47), MI (0.92, 0.83), ischemic stroke (0.52, 0.74), revascularization (0.71, 0.54), and coronary heart disease-related death (0.83, 0.70). The lack of sufficient evidence for causality persisted in other MR methods, including weighted median and MR-egger. The Mendelian randomization analysis conducted in this study does not support a causal relationship between calculated WBV and CVD.