rapid and accurate multiple testing correction and power estimation for millions of correlated markers快速和准确的多个测试校正和功率估计为数以百万计的相关标记.pdfVIP

Rapid and Accurate Multiple Testing Correction and Power Estimation for Millions of Correlated Markers 1 1 2,3 Buhm Han , Hyun Min Kang , Eleazar Eskin * 1 Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, United States of America, 2 Department of Computer Science, University of California Los Angeles, Los Angeles, California, United States of America, 3 Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America Abstract With the development of high-throughput sequencing and genotyping technologies, the number of markers collected in genetic association studies is growing rapidly, increasing the importance of methods for correcting for multiple hypothesis testing. The permutation test is widely considered the gold standard for accurate multiple testing correction, but it is often computationally impractical for these large datasets. Recently, several studies proposed efficient alternative approaches to the permutation test based on the multivariate normal distribution (MVN). However, they cannot accurately correct for multiple testing in genome-wide association studies for two reasons. First, these methods require partitioning of the genome into many disjoint blocks and ignore all correlations between markers from different blocks. Second, the true null distribution of the test statistic often fails to follow the asymptotic distribution at the tails of the distribution. We propose an accurate and efficient method for multiple testing correction in genome-wide association studies—SLIDE. Our method accounts for all correlation within a sliding window and corrects for the departure of the true null distribution of the statistic from the asymptotic distributi