The analysis of whole-genome sequencing studies is challenging due to the large number of rare variants in noncoding regions and the lack of natural units for testing. We propose a statistical method to detect and localize rare and common risk variants in whole-genome sequencing studies based on a recently developed knockoff framework. It can (1) prioritize causal variants over associations due to linkage disequilibrium thereby improving interpretability; (2) help distinguish the signal due to rare variants from shadow effects of significant common variants nearby; (3) integrate multiple knockoffs for improved power, stability, and reproducibility; and (4) flexibly incorporate state-of-the-art and future association tests to achieve the benefits proposed here. In applications to whole-genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP) and COPDGene samples from NHLBI Trans-Omics for Precision Medicine (TOPMed) Program we show that our method compared with conventional association tests can lead to substantially more discoveries.

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Recent advances in genome sequencing and imputation technologies provide an exciting opportunity to comprehensively study the contribution of genetic variants to complex phenotypes. However, our ability to translate genetic discoveries into mechanistic insights remains limited at this point. In this paper, we propose an efficient knockoff-based method, GhostKnockoff, for genome-wide association studies (GWAS) that leads to improved power and ability to prioritize putative causal variants relative to conventional GWAS approaches. The method requires only Z-scores from conventional GWAS and hence can be easily applied to enhance existing and future studies. The method can also be applied to meta-analysis of multiple GWAS allowing for arbitrary sample overlap. We demonstrate its performance using empirical simulations and two applications: (1) a meta-analysis for Alzheimer’s disease comprising nine overlapping large-scale GWAS, whole-exome and whole-genome sequencing studies and (2) analysis of 1403 binary phenotypes from the UK Biobank data in 408,961 samples of European ancestry. Our results demonstrate that GhostKnockoff can identify putatively functional variants with weaker statistical effects that are missed by conventional association tests.

In array signal processing, the direction of arrivals (DOAs) of the received signals are estimatedby measuring the relative phases among antennas; hence, the estimation performance is reducedby the inconsistency among antennas. In this paper, the DOA estimation problem of the uniformlinear array (ULA) is investigated in the scenario with phase errors among the antennas, and adiagonal matrix composed of phase errors is used to formulate the system model. Then, by using thecompressed sensing (CS) theory, we convert the DOA estimation problem into a sparse reconstructionproblem. A novel reconstruction method is proposed to estimate both the DOA and the unknownphase errors, iteratively. The phase errors are calculated by a gradient descent method with thetheoretical expressions. Simulation results show that the proposed method is cost-efficient andoutperforms state-of-the-art methods regarding the DOA estimation with unknown phase errors.

The performance of a direction-finding system is significantly degraded by the imperfection of an array. In this paper, the direction-of-arrival (DOA) estimation problem is investigated in the uniform linear array (ULA) system with the unknown mutual coupling (MC) effect. The system model with MC effect is formulated. Then, by exploiting the signal sparsity in the spatial domain, a compressed-sensing (CS)-based system model is proposed with the MC coefficients, and the problem of DOA estimation is converted into that of a sparse reconstruction. To solve the reconstruction problem efficiently, a novel DOA estimation method, named sparse-based DOA estimation with unknown MC effect (SDMC), is proposed, where both the sparse signal and the MC coefficients are estimated iteratively. Simulation results show that the proposed method can achieve better performance of DOA estimation in the scenario with MC effect than the state-of-the-art methods, and improve the DOA estimation performance about 31.64 % by reducing the MC effect by about 4 dB.