UK Biobank Prospective Cohort Study Research Articles

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.

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content. Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179-1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058-1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132-1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192-7.234), pancreatic cancer (HR 1.976, 95% CI 1.054-3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122-1.593, P = 0.001). FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas.

Risk analysis of air pollutants and types of anemia: a UK Biobank prospective cohort study.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 μg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 μg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study

ObjectiveThe association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank.MethodsA prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan–Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk.ResultsA total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12–1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5–1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1–1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05–1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02–1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3–1.4).ConclusionMetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Walking pace and the time between the onset of noncommunicable diseases and mortality: a UK Biobank prospective cohort study

To estimate time spent in various cardiovascular disease (CVD) and cancer states, according to self-reported walking pace. In total, 391,744 UK Biobank participants were included (median age=57 years; 54.7% women). Data were collected 2006-2010, with follow-up collected in 2021. Usual walking pace was self-defined as slow, steady, average, or brisk. Multistate modeling determined the transition rate and mean sojourn time in and across three different states (healthy, CVD or cancer, and death) upon a time horizon of 10 years. The mean sojourn time in the healthy state was longer, while that in the CVD orcancer state was shorter in individuals reporting an average or brisk walking pace (vs. slow). A 75-year-old woman reporting a brisk walking pace spent, on average, 8.4 years of the next 10 years in a healthy state; an additional 8.0 (95% CI: 7.3, 8.7) months longer than a 75-year-old woman reporting a slow walking pace. This corresponded to 4.3 (3.7, 4.9) fewer months living with CVDorcancer. Similar results were seen in men. Adults reporting an average or brisk walking pace at baseline displayed a lower transition to disease development and a greater proportion of life lived without CVDorcancer. Research was conducted using the UK Biobank resource under Application #33266. The UK Biobank resource can be accessed by researchers on application. Variables derived for this study have been returned to the UK Biobank for future applicants to request. No additional data are available.

Adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations and risk of 14 lifestyle-related cancers in the UK Biobank prospective cohort study

BackgroundThe World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based recommendations which aim to reduce cancer risk. This study investigated associations between adherence, assessed using a standardised scoring system, and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with aspects of lifestyle in the UK.MethodsWe used data from 94,778 participants (53% female, mean age 56 years) from the UK Biobank. Total adherence scores (range 0–7 points) were derived from dietary, physical activity, and anthropometric data. Associations between total score and cancer risk (all cancers combined; and prostate, breast, colorectal, lung, uterine, liver, pancreatic, stomach, oesophageal, head and neck, ovarian, kidney, bladder, and gallbladder cancer) were investigated using Cox proportional hazard models, adjusting for age, sex, deprivation index, ethnicity, and smoking status.ResultsMean total score was 3.8 (SD 1.0) points. During a median follow-up of 8 years, 7296 individuals developed cancer. Total score was inversely associated with risk of all cancers combined (HR: 0.93; 95%CI: 0.90–0.95 per 1-point increment), as well as breast (HR: 0.90; 95%CI: 0.86–0.95), colorectal (HR: 0.90; 95%CI: 0.84–0.97), kidney (HR: 0.82; 95%CI: 0.72–0.94), oesophageal (HR: 0.84; 95%CI: 0.71–0.98), ovarian (HR: 0.76; 95%CI: 0.65–0.90), liver (HR: 0.78; 95%CI: 0.63–0.97), and gallbladder (HR: 0.70; 95%CI: 0.53–0.93) cancers.ConclusionsGreater adherence to lifestyle-based recommendations was associated with reduced risk of all cancers combined and of breast, colorectal, kidney, oesophageal, ovarian, liver, and gallbladder cancers. Our findings support compliance with the Cancer Prevention Recommendations for cancer prevention in the UK.

Socio-demographic variation in adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations within the UK Biobank prospective cohort study.

The 2018 (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are evidence-based lifestyle recommendations which aim to reduce the risk of cancer worldwide. Sociodemographic factors modulate lifestyle behaviours, and both cancer incidence and survival are socio-economically patterned. We investigated adherence to these recommendations and examined patterns of adherence across sociodemographic subgroups in the UK Biobank cohort. We included 158 415 UK Biobank participants (mean age 56years, 53% female). Total adherence scores were derived from dietary, physical activity and anthropometric data using the 2018 WCRF/AICR standardized scoring system. One-Way analysis of variance (ANOVA) was used to test for differences in total scores and in values for individual score components according to sociodemographic factors and Pearson's Χ2 test to investigate associations between sociodemographic factors according to tertiles of adherence score. Mean total adherence score was 3.85 points (SD 1.05, range 0-7 points). Higher total scores were observed in females, and older (>57years), Chinese or South Asian, and more educated participants. We found significant variations in adherence to individual recommendations by sociodemographic factors including education, Townsend deprivation index and ethnicity. Identifying and understanding lifestyle and dietary patterns according to sociodemographic factors could help to guide public health strategies for the prevention of cancers and other non-communicable diseases.

Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study

Background and aimsCardiovascular risk increases during menopause, so the medical and scientific community should consider women's specific risk factors to prevent cardiovascular disease. This study aims to assess the risk factors for the incidence of major adverse cardiovascular events (MACE) exclusive to postmenopausal women. MethodsWe conducted a prospective cohort study in postmenopausal women aged 40 years and older, who were included in the UK Biobank cohort between 2006 and 2010 and followed to 2021 (12 years). A total of 156,787 women were followed for a median of 12.5 years (nearly 2 million person-years), and MACE risk was assessed using Fine-Gray competing risk models. ResultsThe cumulative incidence of cardiovascular morbidity and mortality was 1.2% (0.97 cases per 1000 women-years). Not having taken birth control pills, not having children, and early menarche (≤12 years) were independently associated with cardiovascular morbidity and mortality. ConclusionsRisk factors for cardiovascular disease that are specific to women include early menarche, not having taken oral contraceptives, and reproductive history, and this relationship is independent of classic cardiovascular risk factors.

Skewness in Body fat Distribution Pattern Links to Specific Cardiometabolic Disease Risk Profiles.

Fat distribution pattern could help determine cardiometabolic risk profile. This study aimed to evaluate the association of balance/imbalance between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) with incident type 2 diabetes (T2D) and cardiovascular disease (CVD) in the UK Biobank prospective cohort study. Magnetic resonance images of 40 174 participants were analyzed for VAT, aSAT, and LF using AMRA® Researcher. To assess fat distribution patterns independent of body mass index (BMI), fat z-scores (z-VAT, z-aSAT, z-LF) were calculated. Participants without prevalent T2D/CVD (N = 35 138) were partitioned based on balance between (1) z-VAT and z-LF (z-scores = 0 as cut-points for high/low), (2) z-VAT and z-aSAT, and (3) z-LF and z-aSAT. Associations with T2D/CVD were investigated using Cox regression (crude and adjusted for sex, age, BMI, lifestyle, arterial hypertension, statin treatment). T2D was significantly associated with z-LF (hazard ratio, [95% CI] 1.74 [1.52-1.98], P < .001) and z-VAT (1.70 [1.49-1.95], P < .001). Both remained significant after full adjustment. For z-scores balance, strongest associations with T2D were z-VAT > 0 and z-LF > 0 (4.61 [2.98-7.12]), z-VAT > 0 and z-aSAT < 0 (4.48 [2.85-7.06]), and z-LF > 0 and z-aSAT < 0 (2.69 [1.76-4.12]), all P < .001. CVD was most strongly associated with z-VAT (1.22 [1.16-1.28], P < .001) which remained significant after adjustment for sex, age, BMI, and lifestyle. For z-scores balance, strongest associations with CVD were z-VAT > 0 and z-LF < 0 (1.53 [1.34-1.76], P < .001) and z-VAT > 0 and z-aSAT < 0 (1.54 [1.34-1.76], P < .001). When adjusted for sex, age, and BMI, only z-VAT > 0 and z-LF < 0 remained significant. High VAT in relation to BMI (z-VAT > 0) was consistently linked to both T2D and CVD; z-LF > 0 was linked to T2D only. Skewed fat distribution patterns showed elevated risk for CVD (z-VAT > 0 and z-LF < 0 and z-VAT > 0 and z-aSAT < 0) and T2D (z-VAT > 0 and z-aSAT < 0).

115 Association between muscle strength, body composition and stroke incidence- findings from the UK biobank prospective cohort study

Abstract Background Stroke incidence is growing. Muscle strength and muscle mass are inversely associated with cardiovascular health and the ageing process. The aim of this study was to examine the association between components of body composition and incident stroke. Methods UK Biobank is a prospective, population-based study wherein 348,198 participants aged 40–69 years (56% women) were recruited. The associations of handgrip strength and muscle mass (kg) with stroke incidence over follow-up were investigated using Cox-proportional hazard models. Results Among 348,198 participants, 5,480 (0.02%) participants developed a fatal or non-fatal stroke event over the mean follow-up period of 8.92 (SD 1.15) years. Findings demonstrated inverse and independent associations between hand grip strength and stroke incidence (HR: 0.92, 95% CI 0.89; 0.95, p &amp;lt; 0.001) and stroke mortality (HR: 0.85, 95% CI 0.78; 0.92, p = 0.005) in the full-adjusted models. Findings also show inverse associations between body fat and stroke incidence (HR: 0.93, 95% CI 0.87; 0.99, p = 0.02) and stroke mortality (HR: 0.83, 95% CI 0.71; 1.00, p = 0.02). Muscle mass was not associated with stroke risk or mortality. Conclusion Handgrip strength and body fat were inversely associated with a higher risk of stroke among middle-aged participants in this population-based cohort study. These findings support the importance of body composition and muscle strength evaluation in screening for stroke risk among adults 40+ years old without pre-existing disease.

PTFS04-04-23 Associations Between an Extreme Obesity Phenotype and Endometrial Cancer – Findings From the UK Biobank Prospective Cohort Study

PTFS04-04-23 Associations Between an Extreme Obesity Phenotype and Endometrial Cancer – Findings From the UK Biobank Prospective Cohort Study

Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: prognostic insights from UK Biobank

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute for Health and Care Research British Cardiovascular Society. Background Cardiovascular magnetic resonance imaging (CMR) can estimate left ventricular filling pressure (LVFP). The relationship between LVFP, determined by CMR measurements, and established risk factors for cardiovascular disease is unknown. This study quantifies these associations and investigates the prognostic value of CMR-derived LVFP compared to known risk factors for cardiovascular disease. Methods Using data from the UK Biobank prospective observational cohort study, CMR-derived LVFP was calculated using a model incorporating left atrial volume and left ventricular mass. Logistic regression was used to explore the relationships between raised LVFP (≥15mmHg) and typical cardiovascular risk factors. The non-linear relationship between LVFP and age was analysed using ordinary least squares regression and a restricted cubic spline of age with nine knots. Cox proportional hazards regression was used to analyse the relationships between typical cardiovascular risk factors and CMR-derived LVFP, and outcomes of incident heart failure and major adverse cardiovascular events. Results In this prospective population-based cohort study, 39,163 UK Biobank participants had CMR with adequate image quality. In a multivariable logistic regression model, male sex (OR 4.55, 95% CI 3.85–5.42, p&amp;lt;0.001), age (OR 1.89, 95% CI 1.72 - 2.09, per decade increment, p&amp;lt;0.001), BMI (OR 1.57, 95% CI 1.48–1.67, per SD increment, p&amp;lt;0.001), and hypertension (OR 1.46, 95% CI 1.26–1.68, p&amp;lt;0.001) were associated with increased odds of raised LVFP (Figure 1a). A non-linear regression model of the relationship between age and LVFP, adjusted for all covariables studied, showed little correlation between CMR-derived LVFP and age until 70 years, after which LVFP increased rapidly with age (Figure 2). In multivariable Cox regression models, elevated CMR-derived LVFP was associated with increased hazard of incident heart failure (HR 3.31, 95% CI 1.99–5.49, p&amp;lt;0.001) but not MACE (HR 1.33, 95% CI 0.86–2.07, p = 0.20) (Figure 1b). Conclusions Raised LVFP, as determined using CMR, is independently associated with male sex, age, BMI and hypertension. CMR-derived LVFP is independently associated with incident heart failure. These findings may have implications for clinical risk stratification, targeted population screening strategies and public health measures to reduce the risk of heart failure development.

Dose–response relationship between device-measured physical activity and incident type 2 diabetes: findings from the UK Biobank prospective cohort study

BackgroundMost studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose–response relationship between device-measured PA and incident type 2 diabetes.MethodsThis prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework.ResultsThe median follow-up period was 6.3 years (IQR: 5.7–6.8), with 591 participants developing type 2 diabetes. Compared to those achieving < 150 min/week of moderate PA, people achieving 150–300, 300–600 and > 600 min/week were at 49% (95% CI 62–32%), 62% (95% CI 71–50%) and 71% (95% CI 80–59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving < 25 min/week, individuals achieving 25–50, 50–75 and > 75 min/week were at 38% (95% CI 48–33%), 48% (95% CI 64–23%) and 64% (95% CI 78–42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively.ConclusionsPA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction.Trial registrationThe UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011).

Sleep patterns, genetic susceptibility, and risk of new-onset gout: The UK Biobank prospective cohort study

ObjectiveThe association between sleep behaviors and gout risk remains uncertain. We aimed to evaluate the relationship of sleep patterns based on a combination of five major sleep behaviors with the risk of new-onset gout, and to explore whether genetic risks of gout may modify this association in the general population. Methods403,630 participants without gout at baseline in UK Biobank were included. A healthy sleep score was created by combining five major sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Genetic risk score for gout was calculated based on 13 single nucleotide polymorphisms (SNPs) with independently significant genome-wide association with gout. The primary outcome was new-onset gout. ResultsDuring a median follow-up duration of 12.0 years, 4270 (1.1%) participants developed new-onset gout. Compared to participants with poor sleep patterns (0 ≤ healthy sleep score ≤ 1), those with healthy sleep patterns (4 ≤ healthy sleep score ≤ 5) had a significantly lower risk of new-onset gout (HR, 0.79; 95% CI: 0.70–0.91). Moreover, the significantly lower risk of new-onset gout associated with healthy sleep patterns were mainly found in those with low (HR, 0.68; 95%CI: 0.53–0.88), or intermediate genetic risks of gout (HR, 0.78; 95%CI: 0.62–0.99), but not in participants with high genetic risks of gout (HR, 0.95; 95%CI: 0.77–1.17) (P for interaction =0.043). ConclusionsAmong the general population, a healthy sleep pattern was associated with a significant lower of new-onset gout risk, especially in those with lower genetic risks of gout.

Effects of residential greenness and genetic predisposition on hemoglobin A1c and type 2 diabetes: Gene-environment interaction analysis from a nationwide study

BackgroundCurrent evidence on the relations of residential greenness with glucose homeostasis and type 2 diabetes (T2D) remained largely uncertain. Most importantly, no prior studies have investigated whether genetic predisposition modifies the above associations. MethodsWe leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010. Residential greenness was assessed by using the Normalized Difference Vegetation Index, and the weighting T2D-specific genetic risk score (GRS) was constructed based on previously published genome-wide association studies. Linear regression models and logistic regression models were used to investigate associations of residential greenness with glycated hemoglobin (HbA1c) and T2D prevalence, respectively. Interaction models explored whether genetic predisposition modifies greenness-HbA1c/T2D associations. ResultsAmong 315,146 individuals (mean [SD] age, 56.59 [8.09] years), each one-unit increase in residential greenness was associated with reduction in HbA1c (β: −0.87, 95% CI: −1.16 to −0.58) and a 12% decrease in odds of T2D (OR: 0.88, 95% CI: 0.79 to 0.98), respectively. Additionally, interaction analyses further demonstrated that residential greenness and genetic risk had cumulative effects on HbA1c and T2D. Compared with individuals who were exposed to low greenness and had high GRS, participants with low GRS and high greenness had a significant decline in HbA1c (β: −2.96, 95% CI: −3.10 to −2.82, P for interaction = 0.04) and T2D (OR: 0.47, 95% CI: 0.45 to 0.50, P for interaction = 0.09). ConclusionsWe add novel evidence that residential greenness has protective effects on glucose metabolism and T2D, and those beneficial effects can be amplified by low genetic risk. Our findings may facilitate the improvement of the living environment and the development of prevention strategies by considering genetic susceptibility to T2D.

Associations of Physical Activity With Breast Cancer Risk: Findings From the UK Biobank Prospective Cohort Study.

Although physical activity (PA) has been consistently associated with breast cancer, existing evidence is limited to self-reported physical activity, which is prone to dilution bias. Therefore, this aims to examine the associations of device-measured PA domains with breast cancer risk and whether it differs by menopausal status. Prospective cohort study. Data from 48,286 women from the UK Biobank cohort were analyzed. A wrist triaxial accelerometer was used to collect physical activity data for light, moderate, vigorous, moderate to vigorous, and total PA. Cox proportional models were performed to examine the association between PA domains, menopausal status, and breast cancer risk. Eight hundred thirty-six breast cancer cases were diagnosed during a median of 5.4years (interquartile range: 4.7-5.9). For total PA, those in the most active quartile had a 26% lower risk of breast cancer (Hazard ratio [HR]: 0.74; 95% confidence interval [CI], 0.61-0.91) compared with those least active. Similar results were observed for light PA (HR: 0.79; 95% CI, 0.64-0.96), and moderate to vigorous PA (HR: 0.78; 95% CI, 0.64-0.96). However, moderate PA (HR: 0.73; 95% CI, 0.44-1.19) and vigorous PA (HR: 0.77; 95% CI, 0.56-1.05) was nonsignificant. No evidence of interaction between PA domains and menopause status was found (P > .10). High levels of PA are associated with a lower risk of breast cancer with similar magnitude of associations observed across different intensity domains.

Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study

BackgroundThe identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia.MethodsWe used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested.ResultsHigher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65–0.91; PYRAMID: HR = 0.86, 95% CI = 0.73–1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia.ConclusionsHigher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

Estimating the effect of physical activity on cognitive function within the UK Biobank cohort.

Physical activity (PA) has been associated with benefits for cognitive function (CF), but previous estimates of the strength of this relationship may have been biased due to limitations in statistical modelling practices that are common among observational studies. We aimed to address this by using a rigorously constructed conceptual causal model to guide an empirical analysis estimating the effect of PA on CF in the UK Biobank cohort of middle-aged and older adults. This study analysed a subsample of 334 227 adults from the UK Biobank prospective cohort study. PA was measured subjectively by self-report and by device using accelerometry, and CF was measured using objective cognitive tests. Composite CF measures were derived to represent general and domain-specific performance. Effect coefficients were estimated using regression models, adjusting for a wide range of confounders specified by the assumed causal model, including genetic risk factors, and relevant health, sociodemographic and behavioural variables from across the lifespan. Results indicated very small effect sizes (standardized mean difference estimates all <0.01) of inconsistent direction, for both cross-sectional and longitudinal analyses. The expected protective effect of PA on CF was not observed. This may reflect selection bias within UK Biobank, or the relatively young age of the sample at follow-up.

Association between blood N-3 fatty acid levels and the risk of coronavirus disease 2019 in the UK Biobank

BackgroundThe role of nutritional status and the risk of contracting and/or experiencing adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unclear. Preliminary studies suggest that higher n-3 PUFA intakes are protective. ObjectivesThis study aimed to compare the risk of 3 coronavirus disease 2019 (COVID-19) outcomes (testing positive for SARS-CoV-2, hospitalization, and death) as a function of the baseline plasma DHA levels. MethodsThe DHA levels (% of total fatty acids [FAs]) were measured by nuclear magnetic resonance. The 3 outcomes and relevant covariates were available for 110,584 subjects (hospitalization and death) and for 26,595 ever-tested subjects (positive for SARS-CoV-2) in the UK Biobank prospective cohort study. Outcome data between 1 January, 2020, and 23 March, 2021, were included. The Omega-3 Index (O3I) (RBC EPA + DHA%) values across DHA% quintiles were estimated. The multivariable Cox proportional hazards models were constructed, and linear (per 1 SD) relations with the risk of each outcome were computed as HRs. ResultsIn the fully adjusted models, comparing the fifth to the first DHA% quintiles, the HRs (95% confidence intervals) for testing positive, being hospitalized, and dying with COVID-19 were 0.79 (0.71, 0.89, P < 0.001), 0.74 (0.58, 0.94, P < 0.05), and 1.04 (0.69–1.57, not significant), respectively. On a per 1-SD increase in DHA% basis, the HRs for testing positive, hospitalization, and death, were 0.92 (0.89, 0.96, P < 0.001), 0.89 (0.83, 0.97, P < 0.01), and 0.95 (0.83, 1.09), respectively. The estimated O3I values across DHA quintiles ranged from 3.5% (quintile 1) to 8% (quintile 5). ConclusionsThese findings suggest that nutritional strategies to increase the circulating n-3 PUFA levels, such as increased consumption of oily fish and/or use of n-3 FA supplements, may reduce the risk of adverse COVID-19 outcomes.

Walking pace, handgrip strength, age, APOE genotypes, and new-onset dementia: the UK Biobank prospective cohort study

BackgroundThe independent and additive associations of walking pace and grip strength on dementia risk and the potential modifying effects of age, APOE phenotypes, and other dementia risk factors on the walking pace and dementia relationships demand further clarification. We aimed to investigate the independent and additive relationships of walking pace and handgrip strength on the risk of new-onset dementia and examine the potentially modifying effects of age, APOE phenotypes, lifestyle factors, and family history of dementia in the relationships.MethodsA total of 495,700 participants from the UK Biobank, who were free of dementia at baseline, were included in this study. Walking pace was self-defined as slow, average, or brisk. Handgrip strength was assessed by dynamometer and was divided into sex-specific quartiles. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. Other dementia risk factors, including education, physical activity, hypertension, depression, diabetes, and family history of dementia, were also collected. The primary outcome was new-onset all-cause dementia.ResultsOver a median follow-up duration of 12.0 years, 3986 (0.8%) participants developed new-onset all-cause dementia. Compared with those with slow walking pace, participants with average (HR, 0.61; 95%CI: 0.55–0.68) or brisk (HR, 0.59; 95%CI: 0.52–0.67) walking pace had a significantly lower risk of new-onset all-cause dementia. Moreover, compared with those with both slow walking pace and lower handgrip strength (the first quartile), the lowest risk of new-onset all-cause dementia was observed in participants with both average or brisk walking pace and higher handgrip strength (the 2–4 quartiles) (HR, 0.45; 95%CI: 0.40–0.52). Notably, the negative relationship between walking pace and the risk of new-onset all-cause dementia was significantly reduced as APOE ε4 dosage increased (APOE ε4 dosages = 0 or 1: brisk vs. slow: HR, 0.55; 95%CI: 0.48–0.63; vs. APOE ε4 dosages = 2: brisk vs. slow: HR, 1.14; 95%CI: 0.77–1.68; P for interaction = 0.001) or age increased (< 58 [median]: brisk vs. slow: HR, 0.27; 95%CI: 0.18–0.41; vs. ≥ 58 years: brisk vs. slow: HR, 0.55; 95%CI: 0.48–0.63; P for interaction = 0.007).ConclusionsWalking pace was inversely associated with new-onset dementia in the general population, especially in younger participants and those with lower APOE ε4 dosage. Participants with both faster walking pace and higher handgrip strength had the lowest risk of dementia, suggesting that maintaining both high handgrip strength and fast walking pace may be a more comprehensive strategy for preventing dementia risk.