Department of Biostatistics and Bioinformatics, Emory University
Meta-Analysis of Gene-Level Associations for Rare Variants Based on Single-Variant Statistics
Meta-analysis of genome-wide association studies (GWAS) has led to the discoveries of many
common variants associated with complex human diseases. There is a growing recognition
that identifying causa rare variants also requires large-scale meta-analysis. The fact that
association tests with rare variants are performed at the gene level rather than at the variant
level poses unprecedented challenges in the meta-analysis. First, different studies may adopt
different gene-level tests, so the results are not compatible. Second, gene-level tests require
multivariate statistics (i.e., components of the test statistic and their covariance matrix),
which are difficult to obtain. To overcome these challenges, we propose to perform gene-
level tests for rare variants by combining the results of single-variant analysis (i.e., p-values
of association tests and effect estimates) from participating studies. This simple strategy is
possible because of an insight that multivariate statistics can be recovered from single-variant
statistics, together with the correlation matrix of the single-variant test statistics, which can be
estimated from one of the participating studies or from a publicly available database. We show
both theoretically and numerically that the proposed meta-analysis approach provides accurate
control of the type I error and is as powerful as joint analysis of individual participant data.
This approach accommodates any disease phenotype and any study design and produces all
commonly used gene-level tests. An application to the GWAS summary results of the Genetic
Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency
variants associated with human height. The relevant software is freely available.
September 13, 3:00-4:00pm, 796 COE,
Professor Yao Xie,
H. Milton Stewart School of Industrial and Systems Engineering,
Georgia Institute of technology
High-Dimensional Change-Point Detection
Abstract:
How do we quickly detect small solar flares in a large video stream generated by NASA satellites? How do we improve detection by efficient representation of high-dimensional data that is time-varying? Besides astronomical imaging, high-dimensional change-point detection also arises in many other applications including computer network intrusion detection, sensor networks, medical imaging, and epidemiology. In these problems, each dimension of the data is obtained by a sensor, and there are multiple sensors monitoring the emergence of a signal---an abrupt change in the distribution of the observations. The goal is to detect such a signal as soon as possible after it occurs, and make as few false alarms as possible.
Two key challenges in high-dimensional change-point detection are 1) how to extract useful statistics, 2) how to find an efficient representation of the data. Many high-dimensional data exhibit low-dimensional structures such as sparsity, or the data may lie on a low-dimensional manifold. The approach I take is to exploit these low-dimensional structures in change-point detection. I will describe a mixture procedure that exploits sparsity, and MOUSSE, an online algorithm for tracking the evolving data manifold and extracts efficient statistics for change-point detection.