Volume 17, Issue 6

Genome-wide association studies (GWAS) are susceptible to bias due to population stratification (PS). The most widely used method to correct bias due to PS is principal components (PCs) analysis (PCA), but there is no objective method to guide which PCs to include as covariates. Often, the ten PCs with the highest eigenvalues are included to adjust for PS. This selection is arbitrary, and patterns of local linkage disequilibrium may affect PCA corrections. To address these limitations, we estimate genomic propensity scores based on all statistically significant PCs selected by the Tracy-Widom (TW) statistic. We compare a principal components and propensity scores (PCAPS) approach to PCA and EMMAX using simulated GWAS data under no, moderate, and severe PS. PCAPS reduced spurious genetic associations regardless of the degree of PS, resulting in odds ratio (OR) estimates closer to the true OR. We illustrate our PCAPS method using GWAS data from a study of testicular germ cell tumors. PCAPS provided a more conservative adjustment than PCA. Advantages of the PCAPS approach include reduction of bias compared to PCA, consistent selection of propensity scores to adjust for PS, the potential ability to handle outliers, and ease of implementation using existing software packages.

In recent years, a large number of time series microbial community data has been produced in molecular biological studies, especially in metagenomics. Among the statistical methods for time series, local similarity analysis is used in a wide range of environments to capture potential local and time-shifted associations that cannot be distinguished by traditional correlation analysis. Initially, the permutation test is popularly applied to obtain the statistical significance of local similarity analysis. More recently, a theoretical method has also been developed to achieve this aim. However, all these methods require the assumption that the time series are independent and identically distributed. In this paper, we propose a new approach based on moving block bootstrap to approximate the statistical significance of local similarity scores for dependent time series. Simulations show that our method can control the type I error rate reasonably, while theoretical approximation and the permutation test perform less well. Finally, our method is applied to human and marine microbial community datasets, indicating that it can identify potential relationship among operational taxonomic units (OTUs) and significantly decrease the rate of false positives.

Modern bio-technologies have produced a vast amount of high-throughput data with the number of predictors much exceeding the sample size. Penalized variable selection has emerged as a powerful and efficient dimension reduction tool. However, control of false discoveries (i.e. inclusion of irrelevant variables) for penalized high-dimensional variable selection presents serious challenges. To effectively control the fraction of false discoveries for penalized variable selections, we propose a false discovery controlling procedure. The proposed method is general and flexible, and can work with a broad class of variable selection algorithms, not only for linear regressions, but also for generalized linear models and survival analysis.