Blood methylation biomarkers are associated with diabetic kidney disease progression in type 1 diabetes.

Background: DNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort.

Methods: We analysed baseline blood sample-derived DNA methylation (Illumina's EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.

Integrated multiomic analyses: An approach to improve understanding of diabetic kidney disease.

Aim: Diabetes is increasing in prevalence worldwide, with a 20% rise in prevalence predicted between 2021 and 2030, bringing an increased burden of complications, such as diabetic kidney disease (DKD). DKD is a leading cause of end-stage kidney disease, with significant impacts on patients, families and healthcare providers. DKD often goes undetected until later stages, due to asymptomatic disease, non-standard presentation or progression, and sub-optimal screening tools and/or provision.

Insights into the length and breadth of methodologies harnessed to study human telomeres.

Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence.

Mitochondrial related variants associated with cardiovascular traits.

Introduction: Cardiovascular disease (CVD) is responsible for over 30% of mortality worldwide. CVD arises from the complex influence of molecular, clinical, social, and environmental factors. Despite the growing number of autosomal genetic variants contributing to CVD, the cause of most CVDs is still unclear.

Genetic variants affecting mitochondrial function provide further insights for kidney disease.

Background: Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver. Autosomal genetic variation only explains some of the predisposition to kidney disease. Variations in the mitochondrial genome (mtDNA) and nuclear-encoded mitochondrial genes (NEMG) are implicated in susceptibility to kidney disease and CKD progression, but they have not been thoroughly explored.

Donor genetic burden for cerebrovascular risk and kidney transplant outcome.

Background And Hypothesis: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient.

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT).

Stratification of glioma based on stemness scores in bulk and single-cell transcriptomes.

Background: Brain tumours are known to have a high mortality and morbidity rate due to their localised and frequent invasive growth. The concept that glioma resistance could originate from the dissimilarity in the vulnerability of clonogenic glial stem cells to chemotherapeutic drugs and radiation has driven the scientific community to reexamine the comprehension of glioma growth and strategies that target these cells or modify their stemness.

Methods: Based on the enrichment scores of 12 stemness signatures, we identified glioma subtypes in both tumour bulks and single cells by clustering analysis.

When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis.

Objective: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).

Method: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs.

Stakeholder Perceptions of Complementary and Integrative Medicines from People Living with Rare Diseases in Northern Ireland: A Mixed Methods Study.

Introduction: Only 5% of rare diseases have an approved treatment available, therefore patients often utilise complementary and integrative medicines (CIMs) to help manage their condition. Limited high-quality evidence-based studies are available which support the effectiveness of CIM, as it is difficult to show that an outcome is a direct result of the CIM intervention and not due to bias. Patients and healthcare professionals must weigh up the evidence quality, safety, efficacy, practical logistics, and financial implications of utilising CIM for rare diseases.

Albuminuria-Related Genetic Biomarkers: Replication and Predictive Evaluation in Individuals with and without Diabetes from the UK Biobank.

Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes.

Differential Methylation of Telomere-Related Genes Is Associated with Kidney Disease in Individuals with Type 1 Diabetes.

Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored.

Harnessing Genomic Analysis to Explore the Role of Telomeres in the Pathogenesis and Progression of Diabetic Kidney Disease.

The prevalence of diabetes is increasing globally, and this trend is predicted to continue for future decades. Research is needed to uncover new ways to manage diabetes and its co-morbidities. A significant secondary complication of diabetes is kidney disease, which can ultimately result in the need for renal replacement therapy, via dialysis or transplantation.

A genome-wide association study identifies a possible role for cannabinoid signalling in the pathogenesis of diabetic kidney disease.

Diabetic kidney disease (DKD), also known as diabetic nephropathy, is the leading cause of renal impairment and end-stage renal disease. Patients with diabetes are at risk for DKD because of poor control of their blood glucose, as well as nonmodifiable risk factors including age, ethnicity, and genetics. This genome-wide association study (GWAS) was conducted for the first time in the Emirati population to investigate possible genetic factors associated with the development and progression of DKD.

Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant.

Introduction: Kidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.

Differential methylation in CD44 and SEC23A is associated with time preference in older individuals.

Time preference is a measure used to ascertain the level of which individuals prefer smaller, immediate rewards over larger, delayed rewards. We explored how an individual's time preference associates with their epigenetic profile. Time preferences were ascertained by asking participants of the Northern Ireland COhort for the Longitudinal study of Ageing to make a series of choices between two hypothetical income scenarios.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

Needs of informal caregivers of people with a rare disease: a rapid review of the literature.

Objectives: Many people living with a rare disease (RD) are cared for by a family member. Due to a frequent lack of individual RD knowledge from healthcare professionals, the patient and their informal caregiver are frequently obliged to become 'experts' in their specific condition. This puts a huge strain on family life and results in caregivers juggling multiple roles in addition to unique caring roles including as advocate, case manager and medical navigator.

Prevalence and risk factors for age-related macular degeneration in a population-based cohort study of older adults in Northern Ireland using multimodal imaging: NICOLA Study.

Purpose: To report prevalence and risk factor associations for age-related macular degeneration (AMD) and AMD features from multimodal retinal grading in a multidisciplinary longitudinal population-based study of aging in Northern Ireland.

Study Design: Population-based longitudinal cohort study.

Methods: Retinal imaging at the Norther Ireland Cohort for the Longitudinal Aging Study health assessment included stereo Colour Fundus Photography (CFP) (Canon CX-1, Tokyo, Japan) and Spectral-Domain Optical Coherence Tomography (SD-OCT) ((Heidelberg Retinal Angopgraph (HRA)+OCT; Heidelberg Engineering, Heidelberg, Germany).