The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records.

Background: This study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.

Methods: In UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines.

Influence of family history on penetrance of hereditary cancers in a population setting.

Background: We sought to investigate how penetrance of familial cancer syndromes varies with family history using a population-based cohort.

Methods: We analysed 454,712 UK Biobank participants with exome sequence and clinical data (data collected between March 2006 and June 2021). We identified participants with a self-reported family history of breast or colorectal cancer and a pathogenic/likely pathogenic variant in the major genes responsible for hereditary breast cancer or Lynch syndrome.

Weak and pleiotropy robust sex-stratified Mendelian randomization in the one sample and two sample settings.

Background: Mendelian randomization (MR) leverages genetic data as an instrumental variable to provide estimates for the causal effect of an exposure X on a health outcome Y that is robust to confounding. Unfortunately, horizontal pleiotropy-the direct association of a genetic variant with multiple phenotypes-is highly prevalent and can easily render a genetic variant an invalid instrument.

Methods: Building on existing work, we propose a simple method for leveraging sex-specific genetic associations to perform weak and pleiotropy-robust MR analysis.

The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.

Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression.

Higher adiposity and mental health: causal inference using Mendelian randomization.

Higher adiposity is an established risk factor for psychiatric diseases including depression and anxiety. The associations between adiposity and depression may be explained by the metabolic consequences and/or by the psychosocial impact of higher adiposity. We performed one- and two- sample Mendelian randomization (MR) in up to 145 668 European participants from the UK Biobank to test for a causal effect of higher adiposity on 10 well-validated mental health and well-being outcomes derived using the Mental Health Questionnaire (MHQ).

Understanding Factors That Cause Tinnitus: A Mendelian Randomization Study in the UK Biobank.

Objectives: To investigate the causal role of established risk factors and associated conditions to tinnitus and tinnitus severity in the UK Biobank.

Design: The prospective cohort study with large dataset of >500,000 individuals. The analytical sample of 129,731 individuals in the UK Biobank of European descent.

Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank.

Background: People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits.

Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study.

Background: Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis.

Methods And Findings: Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI.

Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis.

Objective: Previously generated genetic risk scores (GRSs) for type 1 diabetes (T1D) have not captured all known information at non-HLA loci or, particularly, at HLA risk loci. We aimed to more completely incorporate HLA alleles, their interactions, and recently discovered non-HLA loci into an improved T1D GRS (termed the "T1D GRS2") to better discriminate diabetes subtypes and to predict T1D in newborn screening studies.

Research Design And Methods: In 6,481 case and 9,247 control subjects from the Type 1 Diabetes Genetics Consortium, we analyzed variants associated with T1D both in the HLA region and across the genome.

Physical Activity in Ankylosing Spondylitis: evaluation and analysis of an eHealth tool.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory condition characterised by spinal arthritis and exercise is often recommended to reduce the symptoms and improve mobility. However, very little evidence exists for the value of exercise in AS.

Objectives: Firstly, this pilot study aimed to evaluate an eHealth tool, the AS Observer, specifically designed to monitor symptoms, quality of life and physical activity in AS, in terms of patient experience and suitability in generating data for epidemiological studies.

Nanoparticle growth and surface chemistry changes in cell-conditioned culture medium.

When biomolecules attach to engineered nanoparticle (ENP) surfaces, they confer the particles with a new biological identity. Physical format may also radically alter, changing ENP stability and agglomeration state within seconds. In order to measure which biomolecules are associated with early ENP growth, we studied ENPs in conditioned medium from A549 cell culture, using dynamic light scattering (DLS) and linear trap quadrupole electron transfer dissociation mass spectrometry.

Structural basis for complement factor H linked age-related macular degeneration.

Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H (FH), which causes a Tyr-to-His substitution at position 402, is linked to approximately 50% of attributable risks for AMD. We present the crystal structure of the region of FH containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface.