Meta-analysis of 49†549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels.

BACKGROUND: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. METHODS: We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. RESULTS: Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. CONCLUSIONS: This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.

A remote access mixed reality teaching ward round.

BACKGROUND: Heterogeneous access to clinical learning opportunities and inconsistency in teaching is a common source of dissatisfaction among medical students. This was exacerbated during the COVID-19 pandemic, with limited exposure to patients for clinical teaching. METHODS: We conducted a proof-of-concept study at a London teaching hospital using mixed reality (MR) technology (HoloLens2™) to deliver a remote access teaching ward round. RESULTS: Students unanimously agreed that use of this technology was enjoyable and provided teaching that was otherwise inaccessible. The majority of participants gave positive feedback on the MR (holographic) content used (n = 8 out of 11) and agreed they could interact with and have their questions answered by the clinician leading the ward round (n = 9). Quantitative and free text feedback from students, patients and faculty members demonstrated that this is a feasible, acceptable and effective method for delivery of clinical education. DISCUSSION: We have used this technology in a novel way to transform the delivery of medical education and enable consistent access to high-quality teaching. This can now be integrated across the curriculum and will include remote access to specialist clinics and surgery. A library of bespoke MR educational resources will be created for future generations of medical students and doctors to use on an international scale.

Contribution of lower physical activity levels to higher risk of insulin resistance and associated metabolic disturbances in South Asians compared to Europeans.

BACKGROUND: Insulin resistance and related metabolic disturbances are major risk factors for the higher T2D risk and associated morbidity and mortality amongst South Asians. The contribution of physical activity to the increased prevalence of insulin resistance and related disturbances amongst South Asians is unknown. METHODS: We recruited 902 South Asian and European men and women, aged 35-85 years from the ongoing LOLIPOP study. Clinical characterisation comprised standardised questionnaire and measurement of height, weight, waist and hip circumference and blood pressure. Fasting bloods were taken for assessment of glucose, insulin, lipids and HbA1c. Physical activity was quantified using a validated accelerometer, Actigraph GT3X+, worn for 7 days. Univariate and multivariate approaches were used to investigate the relationship between ethnicity, physical activity, insulin resistance and related metabolic disturbances. RESULTS: Total physical activity was ~31% (P = 0.01) lower amongst South Asians compared to Europeans (Mean MET.minutes [SD]: 1505.2 [52] vs. 2050.9 [86.6], P<0.001). After adjusting for age and sex, total physical activity had a negative association with HOMA-IR (B [SE]: -0.18 [0.08], P = 0.04) and fasting glucose levels (B[SE]: -0.11 [0.04], P = 0.02). There was no association between physical activity and other glycemic and lipid parameters. Total physical activity per week contributed towards the differences in insulin resistance and associated metabolic disturbances between South Asians and Europeans. CONCLUSION: Lower levels of physical activity may contribute to the increased insulin resistance in South Asians compared to Europeans. Our results suggest that lifestyle modification through increased physical activity may help to improve glucose metabolism and reduce the burden of excess T2D and related complications amongst South Asians.