Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

<p>Abstract</p> <p>Background</p> <p>The identification of genetic variants related to blood lipid levels within a large, population-based and nationally representative study might lead to a better understanding of the genetic contribution to serum lipid levels in the major race/ethnic groups in the U.S. population.</p> <p>Methods</p> <p>Using data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), we examined associations between 22 polymorphisms in 13 candidate genes and four serum lipids: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). Univariate and multivariable linear regression and within-gene haplotype trend regression were used to test for genetic associations assuming an additive mode of inheritance for each of the three major race/ethnic groups in the United States (non-Hispanic white, non-Hispanic black, and Mexican American).</p> <p>Results</p> <p>Variants within <it>APOE </it>(rs7412, rs429358), <it>PON1 </it>(rs854560), <it>ITGB3 </it>(rs5918), and <it>NOS3 </it>(rs2070744) were found to be associated with one or more blood lipids in at least one race/ethnic group in crude and adjusted analyses. In non-Hispanic whites, no individual polymorphisms were associated with any lipid trait. However, the <it>PON1 </it>A-G haplotype was significantly associated with LDL-C and TC. In non-Hispanic blacks, <it>APOE </it>variant rs7412 and haplotype T-T were strongly associated with LDL-C and TC; whereas, rs5918 of <it>ITGB3 </it>was significantly associated with TG. Several variants and haplotypes of three genes were significantly related to lipids in Mexican Americans: <it>PON1 </it>in relation to HDL-C; <it>APOE </it>and <it>NOS3 </it>in relation to LDL-C; and <it>APOE </it>in relation to TC.</p> <p>Conclusions</p> <p>We report the significant associations of blood lipids with variants and haplotypes in <it>APOE</it>, <it>ITGB3, NOS3</it>, and <it>PON1 </it>in the three main race/ethnic groups in the U.S. population using a large, nationally representative and population-based sample survey. Results from our study contribute to a growing body of literature identifying key determinants of plasma lipoprotein concentrations and could provide insight into the biological mechanisms underlying serum lipid and cholesterol concentrations.</p

stageR: a general stage-wise method for controlling the gene-level false discovery rate in differential expression and differential transcript usage

RNA sequencing studies with complex designs and transcript-resolution analyses involve multiple hypotheses per gene; however, conventional approaches fail to control the false discovery rate (FDR) at gene level. We propose stageR, a two-stage testing paradigm that leverages the increased power of aggregated gene-level tests and allows post hoc assessment for significant genes. This method provides gene-level FDR control and boosts power for testing interaction effects. In transcript-level analysis, it provides a framework that performs powerful gene-level tests while maintaining biological interpretation at transcript-level resolution. The procedure is applicable whenever individual hypotheses can be aggregated, providing a unified framework for complex high-throughput experiments

Descriptive characteristics of continuous oximetry measurement in moderate to severe covid-19 patients

Abstract Non-invasive oxygen saturation (SpO2) is a central vital sign used to shape the management of COVID-19 patients. Yet, there have been no report quantitatively describing SpO2 dynamics and patterns in COVID-19 patients using continuous SpO2 recordings. We performed a retrospective observational analysis of the clinical information and 27 K hours of continuous SpO2 high-resolution (1 Hz) recordings of 367 critical and non-critical COVID-19 patients hospitalised at the Rambam Health Care Campus, Haifa, Israel. An absolute SpO2 threshold of 93% most efficiently discriminated between critical and non-critical patients, regardless of oxygen support. Oximetry-derived digital biomarker (OBMs) computed per 1 h monitoring window showed significant differences between groups, notably the cumulative time below 93% SpO2 (CT93). Patients with CT93 above 60% during the first hour of monitoring, were more likely to require oxygen support. Mechanical ventilation exhibited a strong effect on SpO2 dynamics by significantly reducing the frequency and depth of desaturations. OBMs related to periodicity and hypoxic burden were markedly affected, up to several hours before the initiation of the mechanical ventilation. In summary, OBMs, traditionally used in the field of sleep medicine research, are informative for continuous assessment of disease severity and response to respiratory support of hospitalised COVID-19 patients. In conclusion, OBMs may improve risk stratification and therapy management of critical care patients with respiratory impairment

Descriptive characteristics of continuous oximetry measurement in moderate to severe COVID-19 patients

Non-invasive oxygen saturation (SpO2) is a central vital sign that supports the management of COVID-19 patients. However, reports on SpO2 characteristics are scarce and none has analysed high resolution continuous SpO2 in COVID-19. We provide the first analysis of high resolution SpO2 across the spectrum of COVID-19 disease severity and respiratory support. A total of 367 COVID-19 patients’ recordings, comprising 27K hours of continuous SpO2 data, could be retrieved from patients hospitalized at the Rambam Health Care Campus. Using oximetry digital biomarkers (OBM), we quantified SpO2 characteristics and showed that the percentage of time under 93% oxygen saturation threshold is the best single OBM discriminating between critical and non-critical patients. OBMs traditionally used in the field of sleep medicine research, were informative for assessing the patient’s response to respiratory support. In addition, periodicity and hypoxic burden biomarkers were affected up to several hours before the initiation of the mechanical ventilation. Characteristics from high resolution SpO2 signal may enable to anticipate clinically relevant events, monitoring of treatment response and may be indicative of future deterioration.x</jats:p