Weighted selective collapsing strategy for detecting rare and common variants in genetic association study

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) have been used successfully in detecting associations between common genetic variants and complex diseases. However, common SNPs detected by current GWAS only explain a small proportion of heritable variability. With the development of next-generation sequencing technologies, researchers find more and more evidence to support the role played by rare variants in heritable variability. However, rare and common variants are often studied separately. The objective of this paper is to develop a robust strategy to analyze association between complex traits and genetic regions using both common and rare variants.</p> <p>Results</p> <p>We propose a weighted selective collapsing strategy for both candidate gene studies and genome-wide association scans. The strategy considers genetic information from both common and rare variants, selectively collapses all variants in a given region by a forward selection procedure, and uses an adaptive weight to favor more likely causal rare variants. Under this strategy, two tests are proposed. One test denoted by <it>B_wSC</it>is sensitive to the directions of genetic effects, and it separates the deleterious and protective effects into two components. Another denoted by <it>B_wSCd</it>is robust in the directions of genetic effects, and it considers the difference of the two components. In our simulation studies, <it>B_wSC</it>achieves a higher power when the casual variants have the same genetic effect, while <it>B_wSCd</it>is as powerful as several existing tests when a mixed genetic effect exists. Both of the proposed tests work well with and without the existence of genetic effects from common variants.</p> <p>Conclusions</p> <p>Two tests using a weighted selective collapsing strategy provide potentially powerful methods for association studies of sequencing data. The tests have a higher power when both common and rare variants contribute to the heritable variability and the effect of common variants is not strong enough to be detected by traditional methods. Our simulation studies have demonstrated a substantially higher power for both tests in all scenarios regardless whether the common SNPs are associated with the trait or not.</p

Carb­oxy­methyl ursolate monohydrate

In the title compound, C28H50O5·H2O, all of the six-membered rings of the penta­cyclic triterpene skeleton adopt chair conformations. In the crystal, mol­ecules are linked by O—H⋯O and C—H⋯O hydrogen bonds

The Application of Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in the Diagnosis and Therapy of Acute Cerebral Infarction

Diffusion- and perfusion-weighted magnetic resonance imaging (DWI and PWI) was applied for stroke diagnose in 120 acute (< 48 h) ischemic stroke patients. At hyperacute (< 6 h) stage, it is difficult to find out the infarction zone in conventional T1 or T2 image, but it is easy in DWI, apparent diffusion coefficient (ADC) map; when at 3–6-hour stage it is also easy in PWI, cerebral blood flow (CBF) map, cerebral blood volume (CBV) map, and mean transit time (MTT) map; at acute (6–48 h) stage, DWI or PWI is more sensitive than conventional T1 or T2 image too. Combining DWI with ADC, acute and chronic infarction can be distinguished. Besides, penumbra which should be developed in meaning was used as an indication or to evaluate the therapeutic efficacy. There were two cases (< 1.5 h) that broke the model of penumbra because abnormity was found in DWI but not that in PWI, finally they recovered without any sequela

Gynostemma pentaphyllum for dyslipidemia: A systematic review of randomized controlled trials

Objective: To evaluate the lipid-lowering effect and safety of Gynostemma pentaphyllum (GP) used alone or as adjunctive therapy for dyslipidemia. Methods: Eight databases and three clinical trial registries were searched until January 2022. Randomized controlled trials (RCTs) assessing the effectiveness of GP for dyslipidemia were included. Trial quality was assessed using the Cochrane Risk of Bias Tool 2.0. Data were analyzed by RevMan 5.4 with effects estimated as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Results: Twenty-two RCTs involving 2,407 dyslipidemia participants were included. Regarding the risk of bias, 14 RCTs had some concerns, seven RCTs were high, and one trial was low. GP was comparable to n-3 fatty acids (RR 0.89, 95% CI 0.62–1.28) and red yeast rice (RR 0.33, 95% CI 0.1–1.12) on normalization of serum lipids. GP plus n-3 fatty acid was superior in normalization of triglycerides (TG) and total cholesterol (TC) than n-3 fatty acids (RR 1.34, 95% CI 1.01–1.77). GP was similar to lipid-lowering agents (statins, fibrates, and n-3 fatty acids) in regulating TG, TC, and high-density lipoprotein cholesterol (HDL-C). GP plus lipid-lowering agents were superior to lipid-lowering agents in TG (MD −0.65 mmol/L, 95% CI −1.03 to −0.28), LDL-C (MD −0.57 mmol/L, 95% CI −1.07 to −0.08), and HDL-C (MD 0.15 mmol/L, 95% CI 0.11–0.20). GP was inferior to red yeast rice in TC (MD 0.64 mmol/L, 95% CI 0.15–1.13), TG (MD 0.43 mmol/L, 95% CI 0.15–0.71), and HDL-C (MD −0.25 mmol/L, 95% CI −0.47 to −0.04). GP had fewer adverse events than lipid-lowering drugs. Conclusion: Very low certainty evidence showed that GP’s effects on TC, TG, and HDL-C were comparable to that of lipid-lowering agents. Low certainty evidence showed that red yeast rice was superior to GP in TC, TG, and HDL-C. Low to moderate certainty evidence showed that the effects of GP plus lipid-lowering agents were superior to that of lipid-lowering agents on TG, LDL-C, and HDL-C. GP use for more than 8 weeks appears safe