SEARCH · Search PubMed

Results for “UK BIOBANK”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2003

How could primary care meet the informatics needs of UK Biobank? A Scottish proposal.

UK Biobank is an ambitious post-genomic project involving the recruitment and follow-up of 500 000 volunteers aged 45 to 69 years. Many primary care teams will be involved in the study directly or indirectly. The programme of research will use at least five data sources: paper-based questionnaires, blood samples, genotype information derived from the bloods, clinical/prescribing data from the medical records, and data on deaths. We describe three of the key challenges to primary care informatics posed by this project: patient recruitment, confidentiality, and data management. We then describe solutions proposed in Scotland, based on existing technologies. Some of these may be applicable elsewhere in the other Regional Collaborating Centres and other large-scale collaborative projects which rely on primary care informatics.

Aged↗

PubMed2004

Governing UK Biobank: the importance of ensuring public trust.

In the autumn of 2003, UK Biobank published the first draft of its Ethics and Governance Framework. Subsequently, this document has been available for interested parties to comment on and the UK Biobank Board of Directors is expected to adopt the final version in 2004. Here, we aim to contribute to this process and highlight to a wider audience some of the inconsistencies in the issues of consent, governance and right of withdrawal that emerge from the draft of the Framework. These issues will have implications for securing the public trust and long-term support that the success of the project depends on. Therefore, they must be considered carefully because the UK Biobank will be the first ever genetic database of a general population of this size to become operational, and will be used as a model for other projects of this kind.

Biological Specimen Banks↗

PubMed2005

UK Biobank: from concept to reality.

The UK Biobank is a major UK collaborative research project to recruit and follow longitudinally the health of 500,000 volunteers aged between 40-69 years. It will provide important biological samples and environmental exposure data. As such, it will constitute a resource for many future investigations of the separate and combined effects of genetic, environmental and lifestyle factors on human morbidity, mortality and health.

Adult↗

PubMed2005

Securing our genetic health: engendering trust in UK Biobank.

The recent development of genetic databases, or 'biobanks', in a number of countries reflects scientists' and policy makers' beliefs in the future health benefits to be derived from genetics research. In Britain, however, a proposal for a genetic database, UK Biobank, has been the focus of a number of concerns. Establishing consent and legitimacy for any controversial biomedical research involving the participation of human subjects is difficult; it is however, acute for UK Biobank given the scale of the project and the criticisms levelled at it. Analysing recently published documents pertaining to UK Biobank, this article examines how consent for the project has been discursively framed and how this is reflected in its governance. It is argued that the problem of organising consent has been framed narrowly in terms of adherence to a well-established repertoire of institutional mechanisms which serves to limit debate on the substantive issues at stake. There is little evidence of reflection on the adequacy of such mechanisms for dealing with the unique challenges posed by UK Biobank, including achieving the confidence and participation of a population with diverse perspectives on genetic research. It is concluded that a restricted public discourse about UK Biobank may contribute to a decline in confidence in regulatory systems governing biotechnology and science more generally.

Aged↗

PubMed2025

Whole-genome sequencing of 490,640 UK Biobank participants.

Whole-genome sequencing provides an unbiased and complete view of the human genome and enables the discovery of genetic variation without the technical limitations of other genotyping technologies. Here we report on whole-genome sequencing of 490,640 UK Biobank participants, building on previous genotyping effort1. This advance deepens our understanding of how genetics associates with disease biology and further enhances the value of this open resource for the study of human biology and health. Coupling this dataset with rich phenotypic data, we surveyed within- and cross-ancestry genomic associations and identified novel genetic and clinical insights. Although most associations with disease traits were primarily observed in individuals of European ancestries, strong or novel signals were also identified in individuals of African and Asian ancestries. With the improved ability to accurately genotype structural variants and exonic variation in both coding and UTR sequences, we strengthened and revealed novel insights relative to whole-exome sequencing2,3 analyses. This dataset, representing a large collection of whole-genome sequencing data that is available to the UK Biobank research community, will enable advances of our understanding of the human genome, facilitate the discovery of diagnostics and therapeutics with higher efficacy and improved safety profile, and enable precision medicine strategies with the potential to improve global health.

Humans↗

PubMed2024

Whole -genome survival analysis of 144 286 people from the UK Biobank identifies novel loci associated with blood pressure.

This study utilized UK Biobank data from 144 286 participants and employed whole-genome sequencing (WGS) data and time-to-event data over a 12-year follow-up period to identify susceptibility in genetic variants associated with hypertension. Following genotype quality control, 6 319 822 single nucleotide polymorphisms underwent analysis, revealing 31 significant variant-level associations. Among these, 29 were novel - 15 in Fibrillin-2 ( FBN2 ) and 4 in Junctophilin-2 ( JPH2 ). Mendelian randomization utilizing two identified variants (rs17677724 and rs1014754) suggested that a genetically induced decrease in heart FBN2 expression and an increase in adrenal gland JPH2 expression were causally linked to hypertension. Phenome-wide association (PheWAS) analysis using the FinnGen dataset confirmed positive associations of rs17677724 and rs1014754 with hypertension, assessed across 2727 traits in 377 277 individuals. Lastly, rs1014754 positively associated with kallistatin, whereas rs17677724 negatively associated with renin in the Fenland study, suggesting a counterregulatory response to high blood pressure. This study, employing WGS data, identified novel genetic loci and potential therapeutic targets for hypertension.

Humans↗

PubMed2025

Diet Changes and Colorectal Cancer Risk in the UK Biobank.

BACKGROUND: Modifying dietary behaviors into healthier habits may attenuate the risk of colorectal cancer. This study aimed to investigate the association between dietary changes and the risk of colorectal cancer. METHODS: Following dietary recommendations for red and processed meat, fruit and vegetables, and alcohol consumption, we classified 50,640 participants into poor and good adherence groups in the UK Biobank. Changes in dietary habits were defined as stable poor, poor to good, good to poor, and stable to good adherences. A Cox proportional hazard model was used to examine the association between dietary changes and colorectal cancer risk. RESULTS: Women were more likely to follow dietary recommendations than men. After a median of 3.3 years from the latest follow-up, 8,328 (16.4%) participants followed an improved dietary habit and 5,808 (11.5%) participants had a worsened diet. Compared with men who stably consumed fruit and vegetables <5 servings/day, those who increased their consumption to ≥5 servings/day were related to colorectal cancer risk reduction [HR: 0.24 (0.09-0.63)]. However, the beneficial associations of increased fruit and vegetable consumption were not statistically significant in women [HR: 0.41 (0.11-1.56)]. CONCLUSIONS: Our findings support the evidence that increasing fruit and vegetable intake could serve as a beneficial strategy to mitigate colorectal cancer risk in men. IMPACT: Participants from the UK Biobank significantly changed their adherence to dietary recommendations during the follow-up. Increasing fruit and vegetable consumption was inversely associated with colorectal cancer risk among men.

Humans↗

PubMed2026

Genome-wide association, polygenic risk scores, and machine learning for chronic post-surgical pain risk stratification: A UK biobank study.

Chronic post-surgical pain is a prevalent and debilitating complication following surgery, representing a clinical challenge. Despite the established heritability of pain phenotypes, large-scale genetic studies remain limited. This study aimed to identify genetic variants associated with chronic post-surgical pain, develop polygenic risk scores, and integrate these with clinical features for risk prediction. UK Biobank data from 47,836 participants (2490 cases and 45,346 controls) were split into training (80%; n = 38,268) and validation (20%; n = 9568) sets prior to analysis. A genome-wide association study was conducted on the training set only, across 19 million variants, and polygenic risk scores were constructed and integrated with clinical features in a logistic regression framework. Two close, rare, imputed signals crossed the genome-wide significance threshold but lacked local linkage-disequilibrium support, while 220 variants crossed the suggestive threshold. In the held-out validation set, cases had higher mean polygenic risk scores than controls (0.138 vs. -0.021; Cohen's d = 0.16, p < 0.001). A logistic regression model integrating clinical features and polygenic risk scores achieved an area under the curve of 0.639 (95% CI: 0.583-0.693), higher than models using either feature set alone. The polygenic risk score for chronic post-surgical pain was among the most important predictors. Risk stratification revealed the top quartile had 3.84-fold higher odds of chronic post-surgical pain than the bottom quartile (95% CI: 2.00-7.37). These findings suggest a possible modest genetic contribution to chronic post-surgical pain. Polygenic risk scores may complement clinical factors in surgical risk stratification. PERSPECTIVE: Chronic post-surgical pain may have a modest genetic contribution. This UK Biobank study identified over 220 variants at suggestive significance and constructed a polygenic risk score that was significantly elevated in cases. A combined clinical-genomic model achieved a 3.84-fold difference in odds across predicted-risk quartiles.

Chronic post-surgical pain↗

PubMed2025

A genome-wide association study of stroke risk in Asian statin users: evidence from KoGES and UK Biobank.

BACKGROUND: Despite proven efficacy of statins in stroke prevention, genetic factors may influence individual stroke risk among statin users. With increasing precision medicine approaches and growing evidence of population-specific genetic variations, identifying genetic markers that predict stroke risk in statin-treated Asian populations has become critically important for personalized cardiovascular prevention strategies. METHODS: We conducted a genome-wide association study of 1,678 participants using lipid-lowering agents in the Korean Genome and Epidemiology Study (KoGES) cohort. Significant findings were replicated in 2,170 Asian participants on statins from the UK Biobank using an additive genetic model adjusted for relevant covariates. RESULTS: In the discovery analysis, 83 single nucleotide polymorphisms were suggestively associated with stroke (p <1.0 × 10-5). Among these, 21 SNPs in the CDH13 gene were associated with increased stroke risk. The lead SNP, rs7201829, was significantly replicated in the UK Biobank (odds ratio: 2.29, p = 2.39 × 10-5). CONCLUSIONS: This study identified CDH13 as a significant genetic marker associated with stroke risk among Asian statin users. These findings provide the first genome-wide evidence for genetic determinants of stroke susceptibility during statin therapy, supporting the development of personalized prevention strategies in Asian populations.

Aged↗

PubMed2026

Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.

BACKGROUND: In ∼10% of asthma patients, symptoms remain uncontrolled despite maximal treatment, representing an unmet clinical need. The causal variants, genes and pathways underlying genetic risk factors have not been fully elucidated, and it is unclear whether there are unique genetic risk factors for this asthma subtype. METHODS: We used electronic healthcare records linked to UK Biobank to identify asthma patients with high treatment burden and/or worse outcomes. We performed a genome-wide association study (GWAS) with this case population and healthy controls. We sought replication for associated (p≤5×10-6) signals in four independent studies (12 152 cases and 32 316 controls). Replicated signals were fine-mapped and linked to genes and pathways. RESULTS: In total, 7681 participants met our case definition and showed enrichment for adult-onset asthma, female gender and higher body mass index compared to asthma individuals not meeting case criteria. GWAS with 7681 cases and 38 405 controls revealed 21 reproducible association signals that had previously been associated with asthma, but had a larger effect size in our study. Variant-to-gene mapping highlighted 85 candidate genes, five of which were considered high confidence (BACH2, D2HGDH, IL1RL1, RPS26, SMAD3). CONCLUSION: We present the first use of electronic healthcare records in UK Biobank to identify a subtype of asthma enriched for patients with high treatment burden and/or worse outcomes. Our findings support the role of known asthma genes, highlighting genetic risk variants with stronger effect in these groups of patients. The prioritised genes provide potential therapeutic opportunities for this difficult-to-treat patient population.

Journal Article↗

PubMed2026

Genetic Correlation Between Brain Imaging Phenotypes and Externalizing Behavior: A Large-Scale LDSC Analysis of UK Biobank IDPs.

Externalizing has been associated with differences in brain structure and function; however, it remains unclear whether these associations reflect shared common-variant genetic influences. Cross-trait linkage disequilibrium score regression was used to estimate genome-wide genetic correlations between externalizing genome-wide association study (GWAS) results and 3,935 brain imaging-derived phenotypes from the UK Biobank BIG40 resource. The imaging phenotypes covered structural magnetic resonance imaging (MRI), diffusion MRI, susceptibility-weighted imaging, resting-state functional MRI, and task-based functional MRI. Results were included in the primary analysis when the imaging phenotype had positive single-nucleotide polymorphism (SNP) heritability, a heritability Z statistic of at least 1.96, a mean GWAS chi-square statistic of at least 1.02, at least 200,000 regression SNPs, and a complete LDSC result without a fatal error. Technical imaging quality-control phenotypes were excluded from biological inference. Individual results were corrected using the Benjamini-Hochberg false discovery rate procedure. Aggregated Cauchy association tests (ACATs) were used to evaluate evidence across all imaging phenotypes and within predefined imaging categories. Statistical power, simultaneous confidence bounds, and alternative quality-control definitions were examined in sensitivity analyses. Of the 3,935 imaging phenotypes, 3,716 produced estimable genetic correlations, 2,980 met the primary LDSC quality-control criteria, and 2,967 were classified as biological imaging phenotypes. No individual phenotype survived false discovery rate correction. The smallest unadjusted P value was 0.0005, and the minimum adjusted q value was 0.486. The distribution of genetic correlations was centered near zero, with a median genetic correlation of 0.0014 and a median absolute genetic correlation of 0.0338. ACAT provided no evidence of an aggregate association across all biological imaging phenotypes (P = 0.302), and no predefined imaging category survived multiple-testing correction. The median minimum detectable genetic correlation at 80% power was 0.216. Bonferroni-adjusted simultaneous confidence intervals were fully contained within the interval [-0.30, 0.30] for 80.0% of phenotypes in the primary analysis and 88.0% under the stringent heritability quality-control definition. Broad and stringent sensitivity analyses produced the same overall conclusions. In this study, no statistically robust evidence of genome-wide genetic correlations between externalizing and individual UK Biobank brain imaging phenotypes was found. Nevertheless, small, localized, mixed-direction, or developmentally specific genetic effects remain possible.

Journal Article↗

PubMed2026

Large-Scale Plasma Proteomics Enhances Prediction of Liver-Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank.

OBJECTIVE: To develop a protein risk score (ProRS) for predicting liver-related events (LREs) in patients with diabetes and compare its predictive performance with the Fibrosis-4 Index (FIB-4) and an established polygenic risk score. RESEARCH DESIGN AND METHODS: This prospective cohort study included 13 516 individuals with prediabetes and type 2 diabetes (T2D) from the UK Biobank. Cox proportional hazards models and LASSO regression were applied to identify proteins associated with incident LREs and construct the ProRS. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, net reclassification improvement and integrated discrimination improvement. RESULTS: Over a median follow-up of 13.5 years, 171 (1.3%) incident LREs occurred. We identified 877 proteins associated with LRE risk, primarily enriched in inflammatory signalling, extracellular matrix remodelling and complement/coagulation cascades. In the training set, we developed a 24-protein ProRS (C-index, 0.842; 95% CI 0.797-0.884) that stratified individuals into low-, medium- and high-risk groups, with 10-year cumulative incidences of LREs of 0.2%, 1.2% and 14.2%, respectively. Compared with the low-risk group, the hazard ratio for LREs was 57.1 (95% CI 31.9-102) in the high-risk group. In the internal validation set, the ProRS model (C-index, 0.876; 95% CI 0.827-0.920) accurately predicted both short- and long-term LREs and outperformed FIB-4 index (C-index, 0.733; 95% CI 0.657-0.807) and polygenic risk score (C-index, 0.636; 95% CI 0.564-0.706). CONCLUSIONS: The protein risk score demonstrated superior performance compared with the FIB-4 index and the polygenic risk score in predicting incident LREs among individuals with prediabetes and T2D. The score allows stratification of individuals according to liver-related risk, though external validation in multi-ethnic cohorts is warranted.

Humans↗

PubMed2024

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank.

The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases. A total of 6.5% of individuals carry putatively damaging CH variants, 90% of which are only identifiable upon phasing rare variants (MAF < 0.38%). We identify six recessive gene-trait associations (p < 1.68 × 10-7) after accounting for relatedness, polygenicity, nearby common variants, and rare variant burden. Of these, just one is discovered when considering homozygosity alone. Using longitudinal health records, we additionally identify and replicate a novel association between bi-allelic variation in ATP2C2 and an earlier age at onset of chronic obstructive pulmonary disease (COPD) (p < 3.58 × 10-8). Genetic phase contributes to disease risk for gene-trait pairs: ATP2C2-COPD (p = 0.000238), FLG-asthma (p = 0.00205), and USH2A-visual impairment (p = 0.0084). We demonstrate the power of phasing large-scale genetic cohorts to discover phenome-wide consequences of compound heterozygosity.

Humans↗

PubMed2003

UK Biobank: a project in search of a protocol?

Before it has even begun recruiting participants, the UK Biobank project has raised extraordinary passions among scientists. Some scientists are broadly supportive of the project, and feel that it is a scientifically valid, potentially valuable resource, although they still have reservations over the details of the current protocol. Others see it as an ill-conceived, politically motivated project, in which consultations have only been done to give an appearance of legitimacy and in which the scientific case has not been made for its design. There has been resentment over how the protocol has evolved, and the secrecy and legal constraints that surrounded the process for groups bidding to be involved has had the appearance of attempting to stifle debate. For this article even supporters of the project have been unwilling to be quoted on the record. The only point that everyone seems to agree on is that sufficient debate about the project has not taken place.

Aged↗

PubMed2026

Joint effects of childhood adversity and genetic risk for psychosis on psychopathology in the UK Biobank.

BACKGROUND: The individual effects of genetic factors and adverse childhood experiences (ACEs) on risk of psychosis, including schizophrenia (SCZ) and bipolar disorder (BIP), have been widely acknowledged, but their interaction effects on individual psychopathological symptoms remain unclear. METHODS: Based on data from 163,704 individuals in the UK Biobank, we investigated the joint effects of polygenic risk scores (PRSs) of SCZ and BIP and ACEs on psychopathology. ACEs status and 55 psychopathological symptoms from seven domains were measured retrospectively using an online mental health questionnaire in 2016. Recent genome-wide association studies for SCZ and BIP were combined with genotype data to generate PRSs. Logistic regression analyses were then conducted to explore univariate and joint main effects of PRSs and ACEs on psychopathological symptoms, as well as their additive and multiplicative interaction effects. RESULTS: The interaction mechanisms for PRSs and ACEs varied across symptom domains: additive interactions were observed on the depression (RERIBIP-ACEs = 0.20-0.25), anxiety (RERISCZ-ACEs = 0.20; RERIBIP-ACEs = 0.22-0.26), help-seeking (RERISCZ-ACEs = 0.24; RERIBIP-ACEs = 0.23), and cognition domains (RERISCZ-ACEs = -0.23 to -0.17), whereas multiplicative interactions were only detected on the psychotic (betaSCZ-ACEs = -0.543; betaBIP-ACEs = -0.181), mania (betaBIP-ACEs = -0.195), self-harm or suicide (betaSCZ-ACEs = -0.118), and cognitive domains (betaSCZ-ACEs = -0.204 to -0.157). CONCLUSIONS: The interplay mechanisms for genetic liability to SCZ and BIP and ACEs vary across symptom domains. This study reveals heterogeneity in gene-ACEs interaction mechanisms underlying psychosis and may provide personalized guidance for psychological care after ACEs.

Humans↗

PubMed2024

Ribosomal DNA copy number variation associates with hematological profiles and renal function in the UK Biobank.

The phenotypic impact of genetic variation of repetitive features in the human genome is currently understudied. One such feature is the multi-copy 47S ribosomal DNA (rDNA) that codes for rRNA components of the ribosome. Here, we present an analysis of rDNA copy number (CN) variation in the UK Biobank (UKB). From the first release of UKB whole-genome sequencing (WGS) data, a discovery analysis in White British individuals reveals that rDNA CN associates with altered counts of specific blood cell subtypes, such as neutrophils, and with the estimated glomerular filtration rate, a marker of kidney function. Similar trends are observed in other ancestries. A range of analyses argue against reverse causality or common confounder effects, and all core results replicate in the second UKB WGS release. Our work demonstrates that rDNA CN is a genetic influence on trait variance in humans.

Humans↗

PubMed2025

Clinical implications of bone marrow adiposity identified by phenome-wide association and Mendelian randomization in the UK Biobank.

Bone marrow adiposity changes in diverse diseases, but the full scope of these, and whether they are directly influenced by marrow adiposity, remains unknown. To address this, we previously measured the bone marrow fat fraction of the femoral head, total hip, femoral diaphysis, and spine of over 48,000 UK Biobank participants. Here, we first use these data for PheWAS to identify diseases associated with marrow adiposity at each site. This reveals associations with 47 incident diseases across 12 disease categories, including osteoporosis, fracture, type 2 diabetes, cardiovascular diseases, cancers, and other conditions that burden public health worldwide. Intriguingly, type 2 diabetes associates positively with spine bone marrow adiposity but negatively with marrow adiposity at femoral sites. We then establish PRSs based on bone-marrow-fat-fraction-associated SNPs and use PRS-PheWAS and Mendelian randomization to explore causal associations between marrow adiposity and disease. PRS-PheWAS reveals that genetic predisposition to increased marrow adiposity is positively associated with osteoporosis and fractures. Mendelian randomization further suggests that increased marrow adiposity at the diaphysis and total hip is causally associated with osteoporosis. Our findings substantially advance understanding of how marrow adiposity impacts human health and highlight its potential as a biomarker and/or therapeutic target for diverse human diseases.

Humans↗

PubMed2025

Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank.

BACKGROUND: Genetic factors may have a significant influence on the likelihood of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD). The present study was conducted to explore how single-nucleotide polymorphism (SNP) impacts the development of fibrosis in those suffering from NAFLD. MATERIALS AND METHODS: Utilizing the UK Biobank dataset, we conducted a nested case-control analysis among NAFLD participants, defining the case group as those with liver fibrosis and cirrhosis during follow-up. For our in vitro investigations, we employed the LX-2 human hepatic stellate cell line. Our procedures included cultivating these cells, employing SAMM50-rs2073080 plasmid techniques to enhance the expression of recently discovered SNPs, and conducting biochemical assays. To quantify gene expression, we used real-time PCR with fluorescence detection. RESULTS: The study analyzed data from 5467 participants (1094 cases and 4373 controls). Genome-wide association analysis identified nine significant loci, including the novel rs2073080 variant, strongly associated with NAFLD-associated hepatic fibrosis. In vitro TGF-β modeling revealed significant upregulation of α-SMA and COL1A1, confirming model effectiveness. Oxidative stress markers like elevated malondialdehyde (MDA) and reduced catalase (CAT) and superoxide dismutase (SOD) levels indicated liver damage in the TGF-β group. SAMM50-rs2073080 was upregulated in the NAFLD-associated fibrosis model. In vitro experiments on LX-2 cells showed that SAMM50-rs2073080 overexpression led to increased fibrosis, as indicated by higher cellular MDA levels and lower CAT and SOD levels, compared to the vector group. CONCLUSION: Our research highlights a significant association of SAMM50-rs2073080 with the progression of NAFLD to hepatic fibrosis, and the in vitro experiments further corroborated these findings.

Humans↗