Polygenic prediction of body mass index and obesity through the life course and across ancestries.

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.

A Novel High-Intensity Short Interval Dance Intervention (THANDAV) for Non-Communicable Disease Prevention Tailored to Asian Indian Adolescent Girls.

Background: A significant majority of adolescents from lower-middle-income countries do not meet recommendations for daily physical activity. THANDAV (Taking High-Intensity Interval Training [HIIT] ANd Dance to Adolescents for Victory over noncommunicable diseases [NCDs]) is a 10-minute dance intervention incorporating principles of HIIT. The present study evaluated the effect of THANDAV on cardiovascular risk factors and lifestyle behavior in Asian Indian adolescent girls.

Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy.

Purpose: Diabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.

Methods: We conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis.

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.

Deep-learning prediction of cardiovascular outcomes from routine retinal images in individuals with type 2 diabetes.

Background: Prior studies have demonstrated an association between retinal vascular features and cardiovascular disease (CVD), however most studies have only evaluated a few simple parameters at a time. Our aim was to determine whether a deep-learning artificial intelligence (AI) model could be used to predict CVD outcomes from routinely obtained diabetic retinal screening photographs and to compare its performance to a traditional clinical CVD risk score.

Methods: We included 6127 individuals with type 2 diabetes without myocardial infarction or stroke prior to study entry.

Genotype-Guided Asthma Treatment Reduces Exacerbations in Children: Meta-Analysis of Two Randomized Control Trials.

Background: Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment.

Radiogenomics Pilot Study: Association Between Radiomics and Single Nucleotide Polymorphism-Based Microarray Copy Number Variation in Diagnosing Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.

RO and ChRCC are kidney tumours with overlapping characteristics, making differentiation between them challenging. The objective of this research is to create a radiogenomics map by correlating radiomic features to molecular phenotypes in ChRCC and RO, using resection as the gold standard. Fourteen patients (6 RO and 8 ChRCC) were included in the prospective study.

Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease.

Importance: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD.

Objective: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations.

Cohort profile: The Scottish SHARE Mental Health (SHARE-MH) cohort - linkable survey, genetic and routinely collected data for mental health research.

Purpose: The SHARE Mental Health (SHARE-MH) cohort was established to address the paucity of clinical and genetic data available for mental health research. The cohort brings together detailed mental health questionnaire responses, routinely collected electronic health data and genetic data to provide researchers with an unprecedented linkable dataset. This combination of data sources allows researchers to track mental health longitudinally, across multiple settings.

Pharmacogenetics at scale in real-world bioresources: CYP2C19 and clopidogrel outcomes in UK Biobank.

Objective: The impact of CYP2C19 genotype on clopidogrel outcomes is one of the most well established pharmacogenetic interactions, supported by robust evidence and recommended by the Food and Drug Administration and clinical pharmacogenetics implementation consortium. However, there is a scarcity of large-scale real-world data on the extent of this pharmacogenetic effect, and clinical testing for the CYP2C19 genotype remains infrequent. This study utilizes the UK Biobank dataset, including 10 365 patients treated with clopidogrel, to offer the largest observational analysis of these pharmacogenetic effects to date.

Environmental risk factors for respiratory infection and wheeze in young children: A multicentre birth cohort study.

Introduction: Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood.

Methods: Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study.

Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

Objective: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent.

Research Design And Methods: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians.

Amino acid homeostasis is a target of metformin therapy.

Objective: Unexplained changes in regulation of branched chain amino acids (BCAA) during diabetes therapy with metformin have been known for years. Here we have investigated mechanisms underlying this effect.

Methods: We used cellular approaches, including single gene/protein measurements, as well as systems-level proteomics.

A gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance.

Background And Aims: The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma concentrations of the drug and its metabolites. Current pharmacogenetic guidelines require sequencing of the SLCO1B1 gene, which is more expensive and less accessible than genotyping.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.