Bircan, K. O. | Search bioRxiv

bioRxiv2024

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7,000 publications for more than 15,000 traits, from which more than 625,000 lead associations have been curated. Additionally, 85,000 full genome-wide summary statistics datasets - containing association data for all variants in the analysis - are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.

genetics↗

bioRxiv2021

A comparative analysis of current phasing and imputation software

Whole-genome data has become significantly more accessible over the last two decades. This can largely be attributed to both reduced sequencing costs and imputation models which make it possible to obtain nearly whole-genome data from less expensive genotyping methods, such as microarray chips. Although there are many different approaches to imputation, the Hidden Markov Model remains the most widely used. In this study, we compared the latest versions of the most popular Hidden Markov Model based tools for phasing and imputation: Beagle 5.2, Eagle 2.4.1, Shapeit 4, Impute 5 and Minimac 4. We benchmarked them on three input datasets with three levels of chip density. We assessed each imputation software on the basis of accuracy, speed and memory usage, and showed how the choice of imputation accuracy metric can result in different interpretations. The highest average concordance rate was achieved by Beagle 5.2, followed by Impute 5 and Minimac 4, using a reference-based approach during phasing and the highest density chip. IQS and R2 metrics revealed that IMPUTE5 obtained better results for low frequency markers, while Beagle 5.2 remained more accurate for common markers (MAF>5%). Computational load as measured by run time was lower for Beagle 5.2 than Impute 5 and Minimac 4, while Minimac utilized the least memory of the imputation tools we compared. ShapeIT 4, used the least memory of the phasing tools examined, even with the highest density chip. Finally, we determined the combination of phasing software, imputation software, and reference panel, best suited for different situations and analysis needs and created an automated pipeline that provides a way for users to create customized chips designed to optimize their imputation results.

genomics↗