The vast majority of genome-wide association studies (GWAS) risk loci fall in non-coding regions of the genome. One possible hypothesis is that these GWAS risk loci alter the individual's disease risk through their effect on gene expression in different tissues. In order to understand the mechanisms driving a GWAS risk locus, it is helpful to determine which gene is affected in specific tissue types. For example, the relevant gene and tissue may play a role in the disease mechanism if the same variant responsible for a GWAS locus also affects gene expression. Identifying whether or not the same variant is causal in both GWAS and eQTL studies is challenging due to the uncertainty induced by linkage disequilibrium (LD) and the fact that some loci harbor multiple causal variants. However, current methods that address this problem assume that each locus contains a single causal variant. In this paper, we present a new method, eCAVIAR, that is capable of accounting for LD while computing the quantity we refer to as the colocalization posterior probability (CLPP). The CLPP is the probability that the same variant is responsible for both the GWAS and eQTL signal. eCAVIAR has several key advantages. First, our method can account for more than one causal variant in any loci. Second, it can leverage summary statistics without accessing the individual genotype data. We use both simulated and real datasets to demonstrate the utility of our method. Utilizing publicly available eQTL data on 45 different tissues, we demonstrate that computing CLPP can prioritize likely relevant tissues and target genes for a set of Glucose and Insulin-related traits loci. eCAVIAR is available at
The nonlocal Allen-Cahn (NAC) equation is a generalization of the classic Allen-Cahn equation by replacing the Laplacian with a parameterized nonlocal diffusion operator, and satisfies the maximum principle as its local counterpart. In this paper, we develop and analyze first and second order exponential time differencing (ETD) schemes for solving the NAC equation, which unconditionally preserve the discrete maximum principle. The fully discrete numerical schemes are obtained by applying the stabilized ETD approximations for time integration with the quadraturebased finite difference discretization in space. We derive their respective optimal maximum-norm error estimates and further show that the proposed schemes are asymptotically compatible, i.e., the approximate solutions always converge to the classic Allen-Cahn solution when the horizon, the spatial mesh size and the time step size go to zero. We also prove that the schemes are energy stable in the discrete sense. Various experiments are performed to verify these theoretical results and to investigate numerically the relation between the discontinuities and the nonlocal parameters.
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