In the era of big data, univariate models have widely been used as a workhorse tool for quickly producing marginal estimators; and this is true even when in a high-dimensional dense setting, in which many features are “true,” but weak signals. Genome-wide association studies (GWAS) epitomize this type of setting. Although the GWAS marginal estimator is popular, it has long been criticized for ignoring the correlation structure of genetic variants (i.e., the linkage disequilibrium [LD] pattern). In this paper, we study the effects of LD pattern on the GWAS marginal estimator and investigate whether or not additionally accounting for the LD can improve the prediction accuracy of complex traits. We consider a general high-dimensional dense setting for GWAS and study a class of ridge-type estimators, including the popular marginal estimator and the best linear unbiased prediction (BLUP) estimator as two special cases. We show that the performance of GWAS marginal estimator depends on the LD pattern through the first three moments of its eigenvalue distribution. Furthermore, we uncover that the relative performance of GWAS marginal and BLUP estimators highly depends on the ratio of GWAS sample size over the number of genetic variants. Particularly, our finding reveals that the marginal estimator can easily become near-optimal within this class when the sample size is relatively small, even though it ignores the LD pattern. On the other hand, BLUP estimator has substantially better performance than the marginal estimator as the sample size increases toward the number of genetic variants, which is typically in millions. Therefore, adjusting for the LD (such as in the BLUP) is most needed when GWAS sample size is large. We illustrate the importance of our results by using the simulated data and real GWAS. 相似文献
Nonalcoholic fatty liver disease (NAFLD) is a strong stimulant of cardiovascular diseases, affecting one-quarter of the world's population. TBC1 domain family member 25 (TBC1D25) regulates the development of myocardial hypertrophy and cerebral ischemia–reperfusion injury; however, its effect on NAFLD/nonalcoholic steatohepatitis (NASH) has not been reported. In this study, we demonstrated that TBC1D25 expression is upregulated in NASH. TBC1D25 deficiency aggravated hepatic steatosis, inflammation, and fibrosis in NASH. In vitro tests revealed that TBC1D25 overexpression restrained NASH responses. Subsequent mechanistic validation experiments demonstrated that TBC1D25 interfered with NASH progression by inhibiting abnormal lipid accumulation and inflammation. TBC1D25 deficiency significantly promoted NASH occurrence and development. Therefore, TBC1D25 may potentially be used as a clinical therapeutic target for NASH treatment. 相似文献
Journal of Plant Growth Regulation - Zinc is an important micronutrient for the growth and development of human body and plants. Proper use of nitrogen fertilizer and foliar application of Zn have... 相似文献
Water stress is one of the most important factors limiting sustainable crop production. Therefore, the effects of the plant growth regulators (PGRs) fulvic acid (FA), brassinolide (BR), and uniconazole (Uni) on seedling growth and physiology of two maize (Zea mays L.) varieties were evaluated under???0.7 MPa water stress induced by polyethylene glycol-6000. Under drought stress, the PGRs promoted seedling growth, altered the root-to-shoot ratio, and significantly increased root biomass, length, surface area, diameter, and volume. In addition, depending on the PGR, net photosynthesis rate, SPAD value (indicating chlorophyll content), and water use efficiency increased significantly, under drought stress, whereas transpiration rate decreased. The PGRs also significantly increased antioxidant enzyme activities and significantly decreased malondialdehyde accumulation in leaves and roots under drought stress. Zhengdan958 showed greater variation in physiological responses and stronger drought resistance than Xundan20. In alleviating drought stress in maize seedlings, FA had the greatest effects on shoot growth and leaf physiology; Uni exerted its effects by regulating root structure, and BR effects were intermediate. Under drought stress, the three PGRs increased maize seedling growth, which reduced drought stress-induced damage and improved plant ability to resist the adversity. Based on a comprehensive analysis of physiological indices of drought resistance, Uni is recommended as the best PGR to improve maize seedlings resistance to drought.