Recently developed computational methods allow the imputation of human leukocyte antigen (HLA) genes using intergenic single nucleotide polymorphism markers. To improve the imputation accuracy in HLA imputation, it is essential to increase the sample size and the diversity of alleles in the reference panel. Our software, MergeReference, helps achieve this goal by providing a streamlined pipeline for combining multiple reference panels into one.
Alleles ; HLA Antigens ; Humans ; Leukocytes ; Major Histocompatibility Complex ; Polymorphism, Single Nucleotide ; Sample Size

The meta-analysis has become a widely used tool for many applications in bioinformatics, including genome-wide association studies. A commonly used approach for meta-analysis is the fixed effects model approach, for which there are two popular methods: the inverse variance-weighted average method and weighted sum of z-scores method. Although previous studies have shown that the two methods perform similarly, their characteristics and their relationship have not been thoroughly investigated. In this paper, we investigate the optimal characteristics of the two methods and show the connection between the two methods. We demonstrate that the each method is optimized for a unique goal, which gives us insight into the optimal weights for the weighted sum of z-scores method. We examine the connection between the two methods both analytically and empirically and show that their resulting statistics become equivalent under certain assumptions. Finally, we apply both methods to the Wellcome Trust Case Control Consortium data and demonstrate that the two methods can give distinct results in certain study designs.
Case-Control Studies ; Computational Biology ; Genome-Wide Association Study ; Methods* ; Weights and Measures

The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.
Case-Control Studies ; Dataset ; Genome-Wide Association Study ; Humans ; Leukocytes