Estimation of regional polygenicity from GWAS provides insights into the genetic architecture of complex traits.

The number of variants that have a non-zero effect on a trait (i.e. polygenicity) is a fundamental parameter in the study of the genetic architecture of a complex trait. Although many previous studies have investigated polygenicity at a genome-wide scale, a detailed understanding of how polygenicity varies across genomic regions is currently lacking. In this work, we propose an accurate and scalable statistical framework to estimate regional polygenicity for a complex trait. We show that our approach yields approximately unbiased estimates of regional polygenicity in simulations across a wide-range of various genetic architectures. We then partition the polygenicity of anthropometric and blood pressure traits across 6-Mb genomic regions (N = 290K, UK Biobank) and observe that all analyzed traits are highly polygenic: over one-third of regions harbor at least one causal variant for each of the traits analyzed. Additionally, we observe wide variation in regional polygenicity: on average across all traits, 48.9% of regions contain at least 5 causal SNPs, 5.44% of regions contain at least 50 causal SNPs. Finally, we find that heritability is proportional to polygenicity at the regional level, which is consistent with the hypothesis that heritability enrichments are largely driven by the variation in the number of causal SNPs.

Derivation of a cost-saving screening strategy for asymptomatic primary hyperparathyroidism.

BACKGROUND: Our study seeks to find a cost-saving screening strategy in a primary care population for diagnosing primary hyperparathyroidism based on peak serum total calcium level, age, and patient sex. METHODS: Laboratory data resulting from primary care office visits at our institution between January 2016 through December 2017 to evaluate patients who had at least 1 episode of hypercalcemia (≥10.5 mg/dL). For each serum calcium threshold, we calculated the percentage of patients who were found to have an increased parathyroid hormone level (≥65 pg/mL). We determined whether net cost savings could be achieved by screening hypercalcemic patients given their probability of primary hyperparathyroidism and expected cost savings from fracture risk reduction, given their sex and age. RESULTS: From 155,350 unique patients in the study period, a total of 2,271 had a minimum of 1 hypercalcemic lab value. After exclusion criteria, there were 1,326 patients of whom 27.5% had a parathyroid hormone level checked. Cost savings was established at a screening threshold of 10.5 for all patients until age 66 years for men and 69 years for women. For men aged 67-68 y and women aged 70-71 years, the optimal screening threshold was 10.8 mg/dl. CONCLUSION: Cost savings can be achieved by screening hypercalcemic patients with a life expectancy exceeding 16 years, with varying thresholds based on age and sex.

Oculocardiac Reflex During Intravitreal Injection.

Oculocardiac reflex (OCR) has been described to occur with mechanical manipulation of the eye, eyelids or orbit. There are no reports in the literature of OCR during intravitreal injection (IVI). This may be due to the fact that heart rate is not monitored during the procedure. We aimed to evaluate OCR during IVI. A total of 532 patients were enrolled in the study at Asociacion para Evitar la Ceguera en Mexico. Mexico City, Mexico. IVI was performed on one eye in every patient with diabetic retinopathy (DR), age related macular degeneration (AMD) or choroidal neovascularization (CNV) secondary to pathological myopia. Heart rate was monitored with a pulse oximeter before, during and after injection. OCR was defined as a 20% decrease or more of basal heart rate. The population enrolled included 270 females and 262 males with mean age of 63.8 years. A decrease in heart rate of 20% or more occurred in 18 patients during IVI (3.3%; 95% confidence interval 1.85% and 4.92%). OCR was asymptomatic in these patients. OCR occurred in 3.3% of our patients during IVI. Hence, OCR must be considered when performing IVI.