Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects.

Bulk-tissue molecular quantitative trait loci (QTLs) have been the starting point for interpreting disease-associated variants, and context-specific QTLs show particular relevance for disease. Here, we present the results of mapping interaction QTLs (iQTLs) for cell type, age, and other phenotypic variables in multi-omic, longitudinal data from the blood of individuals of diverse ancestries. By modeling the interaction between genotype and estimated cell-type proportions, we demonstrate that cell-type iQTLs could be considered as proxies for cell-type-specific QTL effects, particularly for the most abundant cell type in the tissue. The interpretation of age iQTLs, however, warrants caution because the moderation effect of age on the genotype and molecular phenotype association could be mediated by changes in cell-type composition. Finally, we show that cell-type iQTLs contribute to cell-type-specific enrichment of diseases that, in combination with additional functional data, could guide future functional studies. Overall, this study highlights the use of iQTLs to gain insights into the context specificity of regulatory effects.

Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP, DSP, and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.

Comparison between perfusion index, pleth variability index, and pulse pressure variability for prediction of hypotension during major abdominal surgery under general anaesthesia: A prospective observational study.

Background and Aims: Short-term hypotension after general anaesthesia can negatively impact surgical outcomes. This study compared the predictive potential of the pleth variability index (PVI), pulse pressure variability (PPV), and perfusion index (PI) for anaesthesia-induced hypotension. This study's primary objective was to evaluate the predictive potential of PI, PVI, and PPV for hypotension. Methods: This observational study included 140 adult patients undergoing major abdominal surgery under general anaesthesia. Mean arterial pressure, heart rate, PVI, PPV, and PI were collected at 1-min intervals up to 20 min post anaesthesia induction. Hypotension was assessed at 5-min and 15-min intervals. Receiver operating characteristic (ROC) curves were plotted to determine the diagnostic performance and best cut-off for continuous variables in predicting a dichotomous outcome. Statistical significance was kept at P < 0.05. Results: Hypotension prevalence within 5 and 15 min of anaesthesia induction was 36.4% and 45%, respectively. A PI cut-off of <3.5 had an area under the ROC curve (AUROC) of 0.647 (P = 0.004) for a 5-min hypotension prediction. The PVI's AUROC was 0.717 (P = 0.001) at cut-off >11.5, while PPV's AUROC was 0.742 (P = 0.001) at cut-off >12.5. At 15 min, PVI's AUROC was 0.615 (95% confidence interval 0.521-0.708, P = 0.020), with 54.9% positive predictive value and 65.2% negative predictive value. Conclusion: PVI, PPV, and PI predicted hypotension within 5 min after general anaesthesia induction. PVI had comparatively higher accuracy, sensitivity, specificity, and positive predictive value than PI and PPV when predicting hypotension at 15 min.

Comparability of Measurement of Astigmatism between URk-800F Auto Refracto-keratometer and MS-39 Anterior Segment Optical Coherence Tomography in Patients with Refractive Error.

INTRODUCTION: Accurate refractive error assessment is the first and the most important step of ocular examination. A reliable screening method of refractive status is important for early detection and prevention of blinding complications of uncorrected refractive error. OBJECTIVES: To evaluate the comparability of astigmatism measured by an auto-refractometer (URk-800F) with the measurements of the gold standard anterior segment optical coherence tomography (AS-OCT). MATERIALS AND METHODS: This cross-sectional observational study was conducted in a tertiary eye centre in Kathmandu from February 2023 to June 2023. A total of 100 patients with best corrected visual acuity of ≥ 20/20, spherical refractive error with cylindrical error of more than and equal to -0.75 and no pathology detected on slit lamp examination were taken by consecutive sampling method. Ethical approval was taken for the study. The data were entered into Microsoft Excel and analysed using Bland-Altman analysis. RESULTS: The mean cylindrical power and axis was -2.33 D and 88 degrees for the right eye and -2.32 D and 122 degrees for the left eye respectively, as measured by MS-39 AS-OCT. For URK 800-F Auto-refracto Keratometer, the mean cylindrical power and axis was -2.31 D and 89 degrees for the right eye and -2.27 D and 124 degrees for the left eye. CONCLUSION: The findings of this study conclude that an auto-refractometer can be used as an effective tool for identification of spherical refractive error as well as measurement of accurate cylindrical power and cylindrical axis in low resource primary care settings.

Safety and Efficacy of Low Dose Atropine in Nepalese Children with Progressive Myopia.

INTRODUCTION: Myopia is emerging as a public health emergency worldwide. Low dose atropine has been proven to be safe and efficacious in halting the progression of myopia. OBJECTIVES: Aim of this study was to evaluate safety and efficacy of low dose atropine in Nepalese children with progressive myopia. MATERIALS AND METHODS: It is a prospective non randomized interventional study. Children with myopia progression of >0.5D in the last six months with baseline myopia of -1.5 to -8 Diopter and astigmatism of 3 D or less were prescribed 0.01% atropine daily at bedtime for two years. Demography including age, gender, race, and examinations including anterior and posterior segment, axial length, near point of accommodation and near vision were recorded in all the children. Ocular and systemic side effects were documented. RESULTS: A total of 200 children were enrolled in the study. Mean age was 11.9±2.97 years with 41% female. Baseline mean axial length was 24.47±1 and mean spherical equivalent was 3.69±1.33. Average increase in axial length was 0.18(±0.02), 0.17(±0.02), and 0.19(±0.04) mm in six months, one year, and two years respectively. The increase in spherical equivalence was 0.2 (±0.01), 0.3(±0.02), and 0.3(±0.02)) diopter in six months, one year, and two years respectively. The myopia progression was found more in the Mongolian race compared to the Aryan race. No ocular or systemic side effects were documented. CONCLUSION: Topical low dose atropine appears to be safe and efficacious in halting the progression of myopia in a cohort of Nepalese children. Further randomized control trial on various doses of atropine are recommended.