Despite depression being a leading cause of global disability, neuroimaging studies have struggled to identify replicable neural correlates of depression or explain limited variance. This challenge may, in part, stem from the intertwined state (current symptoms; variable) and trait (general propensity; stable) experiences of depression.

Here, we sought to disentangle state from trait experiences of depression by leveraging a longitudinal cohort and stratifying individuals into four groups: those in remission (‘trait depression group’), those with large longitudinal severity changes in depression symptomatology (‘state depression group’), and their respective matched control groups (total analytic n = 1030). We hypothesized that spatial network organization would be linked to trait depression due to its temporal stability, whereas functional connectivity between networks would be more sensitive to state-dependent depression symptoms due to its capacity to fluctuate.

We identified 15 large-scale probabilistic functional networks from resting-state fMRI data and performed group comparisons on the amplitude, connectivity, and spatial overlap between these networks, using matched control participants as reference. Our findings revealed higher amplitude in visual networks for the trait depression group at the time of remission, in contrast to controls. This observation may suggest altered visual processing in individuals predisposed to developing depression over time. No significant group differences were observed in any other network measures for the trait-control comparison, nor in any measures for the state-control comparison. These results underscore the overlooked contribution of visual networks to the psychopathology of depression and provide evidence for distinct neural correlates between state and trait experiences of depression.

We aimed to evaluate the association of coffee consumption with different additives, including milk and/or sweetener (sugar and/or artificial sweetener), and different coffee types, with new-onset acute kidney injury (AKI), and examine the modifying effects of genetic variation in caffeine metabolism. 194 324 participants without AKI at baseline in the UK Biobank were included. The study outcome was new-onset AKI. During a median follow-up of 11·6 years, 5864 participants developed new-onset AKI. Compared with coffee non-consumers, a significantly lower risk of new-onset AKI was found in coffee consumers adding neither milk nor sugar to coffee (hazard ratio (HR), 0·86; 95 % CI, 0·78, 0·94) and adding only milk to coffee (HR,0·83; 95 % CI, 0·78, 0·89), but not in coffee consumers adding only sweetener (HR,1·14; 95 % CI, 0·99, 1·31) and both milk and sweetener to coffee (HR,0·96; 95 % CI, 0·89, 1·03). Moreover, there was a U-shaped association of coffee consumption with new-onset AKI, with the lowest risk at 2–3 drinks/d, in unsweetened coffee (no additives or milk only to coffee), but no association was found in sweetened coffee (sweetener only or both milk and sweetener to coffee). Genetic variation in caffeine metabolism did not significantly modify the association. A similar U-shaped association was found for instant, ground and decaffeinated coffee consumption in unsweetened coffee consumers, but not in sweetened coffee consumers. In conclusion, moderate consumption (2–3 drinks/d) of unsweetened coffee with or without milk was associated with a lower risk of new-onset AKI, irrespective of coffee type and genetic variation in caffeine metabolism.

Growing evidence indicates a link between diet and depression risk. We aimed to examine the association between an inflammatory diet index and depression utilising extensive data from UK biobank cohort. The energy-adjusted dietary inflammation index (E-DII) was calculated to quantify the potential of daily diet, with twenty-seven food parameters utilised. The E-DII scores were classified into two categories (low v. high) based on median value. To mitigate bias and ensure comparability of participant characteristics, propensity score matching was employed. To ascertain the robustness of these associations, sensitivity analyses were conducted. Subgroup analyses were performed to evaluate the consistency of these associations within different subpopulations. Totally, 152 853 participants entered the primary analyses with a mean age of 56·11 (sd 7·98) years. Employing both univariate and multivariate logistic regression models, adjustments were made for varying degrees of confounding factors (socio-demographics, lifestyle factors, common chronic medical conditions including type 2 diabetes and hypertension). Results consistently revealed a noteworthy positive correlation between E-DII and depression. In the context of propensity score matching, participants displaying higher E-DII scores exhibited an increased likelihood of experiencing incident depression (OR = 1·12, 95 % CI: 1·05, 1·19; P = 0·000316). Subgroup analysis results demonstrated variations in these associations across diverse subpopulations. The E-value for the point-estimate OR calculated from the propensity score matching dataset was 1·48. Excluding individuals diagnosed with type 2 diabetes or hypertension, the findings consistently aligned with the positive association in the primary analysis. These findings suggested that consumption of a diet with higher pro-inflammatory potential might associated with an increase of future depression risk.

Prior research has suggested an inverse correlation between dried fruit intake and type 2 diabetes mellitus (T2DM), yet the causal link remains uncertain. This study seeks to investigate the potential causal impact of dried fruit intake on T2DM, covering cases both with and without various complications, as well as glycaemic traits, using a two-sample Mendelian randomisation (MR) approach. Using MR analysis with genome-wide association study summary statistics, the primary analysis investigated the causal relationship between dried fruit intake and T2DM, both with and without complications, as well as glycaemic traits, employing the inverse variance weighted method. Supplementary analyses were conducted using MR-Egger and the weighted median method. Heterogeneity and intercept tests were utilised to evaluate the robustness of the study outcomes. The results show a significant association between dried fruit intake and T2DM without complications, as well as fasting insulin. Sensitivity analyses confirmed the robustness of the results and the independence from multicollinearity. However, no association was found between dried fruit intake and T2DM with various complications or other glycaemic traits. The significant association between dried fruit intake and T2DM without complications and fasting insulin persisted even after adjusting for BMI. This study offers genetic evidence endorsing the protective effects of dried fruit intake against T2DM, specifically for cases without complications, and in regulating fasting insulin. These findings suggest that dried fruit intake might serve as a primary preventive strategy for T2DM.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

This study aimed to investigate the causal effect of dietary habits on COVID-19 susceptibility, hospitalisation and severity. We used data from a large-scale diet dataset and the COVID-19 Host Genetics Initiative to estimate causal relationships using Mendelian randomisation. The inverse variance weighted (IVW) method was used as the main analysis. For COVID-19 susceptibility, IVW estimates indicated that milk (OR: 0·82; 95 % CI (0·68, 0·98); P = 0·032), unsalted peanut (OR: 0·53; 95 % CI (0·35, 0·82); P = 0·004), beef (OR: 0·59; 95 % CI (0·41, 0·84); P = 0·004), pork (OR: 0·63; 95 % CI (0·42, 0·93); P = 0·022) and processed meat (OR: 0·76; 95 % CI (0·63, 0·92); P = 0·005) were causally associated with reduced COVID-19 susceptibility, while coffee (OR: 1·23; 95 % CI (1·04, 1·45); P = 0·017) and tea (OR: 1·17; 95 % CI (1·05, 1·31); P = 0·006) were causally associated with increased risk. For COVID-19 hospitalisation, beef (OR: 0·51; 95 % CI (0·26, 0·98); P = 0·042) showed negative correlations, while tea (OR: 1·54; 95 % CI (1·16, 2·04); P = 0·003), dried fruit (OR: 2·08; 95 % CI (1·37, 3·15); P = 0·001) and red wine (OR: 2·35; 95 % CI (1·29, 4·27); P = 0·005) showed positive correlations. For COVID-19 severity, coffee (OR: 2·16; 95 % CI (1·25, 3·76); P = 0·006), dried fruit (OR: 1·98; 95 % CI (1·16, 3·37); P = 0·012) and red wine (OR: 2·84; 95 % CI (1·21, 6·68); P = 0·017) showed an increased risk. These findings were confirmed to be robust through sensitivity analyses. Our findings established a causal relationship between dietary habits and COVID-19 susceptibility, hospitalisation and severity.

UK Biobank is an intensively characterised prospective cohort of 500,000 adults aged 40–69 years when recruited between 2006 and 2010. The study was established to enable researchers worldwide to undertake health-related research in the public interest. The existence of such a large, detailed prospective cohort with a high degree of participant engagement enabled its rapid repurposing for coronavirus disease-2019 (COVID-19) research. In response to the pandemic, the frequency of updates on hospitalisations and deaths among participants was immediately increased, and new data linkages were established to national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and primary care health records to facilitate research into the determinants of severe COVID-19. UK Biobank also instigated several sub-studies on COVID-19. In 2020, monthly blood samples were collected from approximately 20,000 individuals to investigate the distribution and determinants of SARS-CoV-2 infection, and to assess the persistence of antibodies following infection with another blood sample collected after 12 months. UK Biobank also performed repeat imaging of approximately 2,000 participants (half of whom had evidence of previous SARS-CoV-2 infection and half did not) to investigate the impact of the virus on changes in measures of internal organ structure and function. In addition, approximately 200,000 UK Biobank participants took part in a self-test SARS-CoV-2 antibody sub-study (between February and November 2021) to collect objective data on previous SARS-CoV-2 infection. These studies are enabling unique research into the genetic, lifestyle and environmental determinants of SARS-CoV-2 infection and severe COVID-19, as well as their long-term health effects. UK Biobank’s contribution to the national and international response to the pandemic represents a case study for its broader value, now and in the future, to precision medicine research.

Over the years, numerous observational studies have substantiated that various dietary choices have opposing effects on CVD. However, the causal effect has not yet been established. Thus, we conducted a Mendelian randomisation (MR) analysis to reveal the causal impact of dietary habits on CVD. Genetic variants strongly associated with 20 dietary habits were selected from publicly available genome-wide association studies conducted on the UK Biobank cohort (n 449 210). Summary-level data on CVD were obtained from different consortia (n 159 836–977 323). The inverse-variance weighted method (IVW) was the primary outcome, while MR-Egger, weighted median and MR Pleiotropy RESidual Sum and Outlier were used to assess heterogeneity and pleiotropy. We found compelling evidence of a protective causal effect of genetic predisposition towards cheese consumption on myocardial infarction (IVW OR = 0·67; 95 % CI = 0·544, 0·826; P = 1·784 × 10−4) and heart failure (IVW OR = 0·646; 95 % CI = 0·513, 0·814; P = 2·135 × 10−4). Poultry intake was found to be a detrimental factor for hypertension (IVW OR = 4·306; 95 % CI = 2·158, 8·589; P = 3·416 × 10−5), while dried fruit intake was protective against hypertension (IVW OR = 0·473; 95 % CI = 0·348, 0·642; P = 1·683 × 10−6). Importantly, no evidence of pleiotropy was detected. MR estimates provide robust evidence for a causal relationship between genetic predisposition to 20 dietary habits and CVD risk, suggesting that well-planned diets may help prevent and reduce the risk of CVD.

‘Dietary variety’ has been identified as a factor associated with food intake. Whilst this relationship may have longer-term benefits for body weight management when eating low-energy, nutrient-dense foods, it may increase the risk of overconsumption (and body adiposity) when foods are high energy density. This study sought to further explore pathways underpinning the relationship between dietary variety and body weight, by considering energy density as a moderating factor and portion size as a mediating factor in this relationship. Using prospective data from the UK Biobank, dietary variety scores (DVS), cumulative portion size and energy density were derived from 24-h dietary recall questionnaires at baseline and follow-up. BMI, whole-body fat percentage and fat-free mass were included as outcomes. Contrary to predictions, linear multiple regression models found some evidence of a negative, direct association between DVS and body weight outcomes at baseline (b = –0·13). Though dietary variety was significantly associated with larger portions across time points (b = 41·86–82·64), a moderated mediation effect was not supported at baseline or follow-up (Index ≤ 0·035). Taken together, these findings provide population-level evidence to support a positive association between variety and food intake, which in turn has potential implications for body weight management, both in terms of moderating food intake and benefitting diet quality.

The present study elucidates the association of intrinsic sugars and free sugars (FS) from all relevant sources with all-cause mortality in the prospective UK Biobank cohort. Sugar intake was assessed in 186 811 UK Biobank participants who completed at least one web-based 24-h dietary recall (Oxford WebQ). Cox proportional hazard regression models for all-cause mortality were used with sugar intake from different sources included as penalised cubic splines to allow non-linear predictor effects. Over a mean follow-up of 12·3 years, 8576 (4·6 %) deaths occurred. FS but not intrinsic sugars were significantly and dose-dependently associated with hazard ratio (HR) for all-cause mortality. The association with all-cause mortality was significant and dose dependent for FS in beverages, but not in solids with the mean (CI) HR at 50 g/d v. 0 g/d consumption at 1·10, 95 % CI (1·07, 1·14) and 1·01, 95 % CI (0·98, 1·03), respectively. Within the beverages subcategories, a significant dose-dependent association with mortality was detected for FS in soda/fruit drinks and milk-based drinks whereas this relation was NS for FS in pure juice and tea/coffee. FS in four different subtypes of solids, i.e. treats, cereals, toppings and sauces, were not positively associated with all-cause mortality. Major findings were robust in sensitivity analyses. In conclusion, only some FS sources were associated with all-cause mortality. Interventions targeting FS subtypes might be most effective concerning mortality if focused on the reduction of soda/fruit drinks and milk-based sugary drinks; however, the present results need to be confirmed by independent studies.

One of the longstanding debates in life-course epidemiology is whether an adverse intrauterine environment, often proxied by birth weight, causally increases the future risk of cardiometabolic disease. The use of a discordant twin study design, which controls for the influence of shared genetic and environmental confounding factors, may be useful to investigate whether this relationship is causal. We conducted a discordant twin study of 120 monozygotic (MZ) and 148 dizygotic (DZ) twin pairs from the UK Biobank to explore the potential causal relationships between birth weight and a broad spectrum of later-life cardiometabolic risk factors. We used a linear mixed model to investigate the association between birth weight and later-life cardiometabolic risk factors for twins, allowing for both within-pair differences and between-pair differences in birth weight. Of primary interest is the within-pair association between differences in birth weight and cardiometabolic risk factors, which could reflect an intrauterine effect on later-life risk factors. We found no strong evidence of association in MZ twins between the within-pair differences in birth weight and most cardiometabolic risk factors in later life, except for nominal associations with C-reactive protein and insulin-like growth factor 1. However, these associations were not replicated in DZ twin pairs. Our study provided no strong evidence for intrauterine effects on later-life cardiometabolic risk factors, which is consistent with previous large-scale studies of singletons testing the potential causal relationship. It does not support the hypothesis that adverse intrauterine environments increase the risk of cardiometabolic disease in later life.