Jack Bowden
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View article: Placental growth plays a key role in the link between maternal glucose levels in pregnancy and risk of preeclampsia
Placental growth plays a key role in the link between maternal glucose levels in pregnancy and risk of preeclampsia Open
Preeclampsia is a serious condition affecting 2-4% of pregnancies globally. However, it is more common in pregnancies with diabetes (e.g. 10-20% in Type 1 diabetes) than in pregnancies without diabetes. In the general population, higher ma…
View article: Using Genetics to Understand Shared Mechanisms Between Hypertension and Type 2 Diabetes Accounting for Adiposity
Using Genetics to Understand Shared Mechanisms Between Hypertension and Type 2 Diabetes Accounting for Adiposity Open
Hypertension and type 2 diabetes (T2D) frequently co-occur, but their shared mechanisms are not fully understood. We investigated diagnostic patterns in 3.6 million primary care records, finding that hypertension precedes T2D by a median o…
View article: Triangulating Instrumental Variable, confounder adjustment and difference-in-difference methods for comparative effectiveness research in observational data
Triangulating Instrumental Variable, confounder adjustment and difference-in-difference methods for comparative effectiveness research in observational data Open
Background Observational studies play an important role in assessing the comparative effectiveness of competing treatments. In clinical trials the randomization of participants to treatment and control groups generally results in balanced …
Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data Open
Background Statins are prescribed to lower LDL cholesterol. Clinical guidelines recommend 30–50% reduction within 3 months, yet many patients do not achieve this. We investigated predictors of LDL-c reduction, treatment adherence, and adve…
View article: Getting to GRIPS with MR-Egger: modelling directional pleiotropy independently of allele coding
Getting to GRIPS with MR-Egger: modelling directional pleiotropy independently of allele coding Open
Mendelian Randomisation Egger regression (MR-Egger) is a popular method for causal inference using single-nucleotide polymorphisms (SNPs) as instrumental variables. It allows all SNPs to have direct pleiotropic effects on the outcome, prov…
View article: Increased risk of asthma in female night shift workers
Increased risk of asthma in female night shift workers Open
Rationale Asthma is more common in females and more common in night shift workers. Since increasing numbers of females are becoming shift workers, it is important to determine if the risk of shift work-associated asthma is higher in female…
View article: Instrumental Variable Methods to Target Hypothetical Estimands With Longitudinal Repeated Measures Data: Application to the STEP 1 Trial
Instrumental Variable Methods to Target Hypothetical Estimands With Longitudinal Repeated Measures Data: Application to the STEP 1 Trial Open
The STEP 1 randomized trial evaluated the effect of taking semaglutide versus placebo on body weight over a 68‐week duration. As with any study evaluating an intervention delivered over a sustained period, nonadherence was observed. This w…
View article: Triangulating Instrumental Variable, confounder adjustment and difference-in-difference methods for comparative effectiveness research in observational data
Triangulating Instrumental Variable, confounder adjustment and difference-in-difference methods for comparative effectiveness research in observational data Open
Background Observational studies play an important role in assessing the comparative effectiveness of competing treatments. In clinical trials the randomization of participants to treatment and control groups generally results in balanced …
View article: Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data
Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data Open
Background Statins are commonly prescribed to lower LDL cholesterol. Clinical guidelines recommend 30-50% reduction within 3 months, yet many patients do not achieve this. We investigated the impact of patient characteristics and genetics …
View article: Pulmonary fibroblast activation during <i>Aspergillus fumigatus</i> infection enhances lung defense via immunomodulation and tissue remodeling
Pulmonary fibroblast activation during <i>Aspergillus fumigatus</i> infection enhances lung defense via immunomodulation and tissue remodeling Open
Aspergillus fumigatus is the etiologic agent of invasive aspergillosis, a life- threatening fungal pneumonia that is initiated by the inhalation of conidia (spores) into the lung. If the conidia are not cleared, they secrete large quantiti…
View article: Estimating and visualising multivariable Mendelian randomization analyses within a radial framework
Estimating and visualising multivariable Mendelian randomization analyses within a radial framework Open
Background Mendelian randomization (MR) is a statistical approach using genetic variants as instrumental variables to estimate causal effects of a single exposure on an outcome. Multivariable MR (MVMR) extends this to estimate the direct e…
View article: Increased risk of asthma in female night shift workers
Increased risk of asthma in female night shift workers Open
Background Asthma is more common in females and more common in night shift workers. Since increasing numbers of females are becoming shift workers it is important to determine if shift work-associated asthma risk is higher in females. Rese…
View article: Sparse Causal Effect Estimation using Two-Sample Summary Statistics in the Presence of Unmeasured Confounding
Sparse Causal Effect Estimation using Two-Sample Summary Statistics in the Presence of Unmeasured Confounding Open
Observational genome-wide association studies are now widely used for causal inference in genetic epidemiology. To maintain privacy, such data is often only publicly available as summary statistics, and often studies for the endogenous cov…
View article: Using clustering of genetic variants in Mendelian randomization to interrogate the causal pathways underlying multimorbidity from a common risk factor
Using clustering of genetic variants in Mendelian randomization to interrogate the causal pathways underlying multimorbidity from a common risk factor Open
Mendelian randomization (MR) is an epidemiological approach that utilizes genetic variants as instrumental variables to estimate the causal effect of an exposure on a health outcome. This paper investigates an MR scenario in which genetic …
View article: Genetics identifies obesity as a shared risk factor for co-occurring multiple long-term conditions
Genetics identifies obesity as a shared risk factor for co-occurring multiple long-term conditions Open
Background Multimorbidity, the co-occurrence of multiple long-term conditions (LTCs), is an increasingly important clinical problem, but often little is known about the underlying causes. Observational studies are highly susceptible to con…
View article: Instrumental Variable methods to target Hypothetical Estimands with longitudinal repeated measures data: Application to the STEP 1 trial
Instrumental Variable methods to target Hypothetical Estimands with longitudinal repeated measures data: Application to the STEP 1 trial Open
The STEP 1 randomized trial evaluated the effect of taking semaglutide vs placebo on body weight over a 68 week duration. As with any study evaluating an intervention delivered over a sustained period, non-adherence was observed. This was …
Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach Open
Aims/hypothesis Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium–glucose cotra…
View article: A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data
A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data Open
Background Multimorbidity, the presence of two or more conditions in one person, is common but studies are often limited to observational data and single datasets. We address this gap by integrating large-scale primary-care and genetic dat…
View article: Exploring and accounting for genetically driven effect heterogeneity in Mendelian Randomization
Exploring and accounting for genetically driven effect heterogeneity in Mendelian Randomization Open
Mendelian randomization uses genetic variants as instrumental variables to estimate the causal effect of a modifiable health exposure or drug target on a downstream outcome. A crucial assumption for accurate estimation of the average causa…
View article: SLCO1B1 Exome Sequencing and Statin Treatment Response in 64,000 UK Biobank Patients
SLCO1B1 Exome Sequencing and Statin Treatment Response in 64,000 UK Biobank Patients Open
The solute carrier organic anion transporter family member 1B1 (SLCO1B1) encodes the organic anion-transporting polypeptide 1B1 (OATP1B1 protein) that transports statins to liver cells. Common genetic variants in SLCO1B1, such as *5, cause…
View article: Robust use of phenotypic heterogeneity at drug target genes for mechanistic insights: Application of <i>cis</i>‐multivariable Mendelian randomization to <i>GLP1R</i> gene region
Robust use of phenotypic heterogeneity at drug target genes for mechanistic insights: Application of <i>cis</i>‐multivariable Mendelian randomization to <i>GLP1R</i> gene region Open
Phenotypic heterogeneity at genomic loci encoding drug targets can be exploited by multivariable Mendelian randomization to provide insight into the pathways by which pharmacological interventions may affect disease risk. However, statisti…
View article: Hyperglycaemia is a causal risk factor for upper limb pathologies
Hyperglycaemia is a causal risk factor for upper limb pathologies Open
Background Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test…
View article: Safety and effectiveness of SGLT2-inhibitors in people with type 2 diabetes over 70: UK population-based study using an Instrumental Variable approach
Safety and effectiveness of SGLT2-inhibitors in people with type 2 diabetes over 70: UK population-based study using an Instrumental Variable approach Open
Objective Older adults are underrepresented in trials, meaning the benefits and risks of glucose lowering agents in this age group are unclear. We applied causal analysis to assess the safety and effectiveness of SGLT2-inhibitors in people…