Fast Analysis of Biobank-Size Data and Meta-Analysis using the BGLR R-package.

Abstract

Analyzing human genomic data from biobanks and large-scale genetic evaluations often requires fitting models with a sample size exceeding the number of DNA markers used (n > p). For instance, developing Polygenic Scores (PGS) for humans and genomic prediction for genetic evaluations of agricultural species may require fitting models involving a few thousand SNPs using data with hundreds of thousands of samples. In such cases, computations based on sufficient statistics are more efficient than those based on individual genotype-phenotype data. Additionally, software that admits sufficient statistics as inputs can be used to analyze data from multiple sources jointly without the need to share individual genotype-phenotype data. Therefore, we developed functionality within the BGLR R-package that generates posterior samples for Bayesian shrinkage and variable selection models from sufficient statistics. In this article, we present an overview of the new methods incorporated in the BGLR R-package, demonstrate the use of the new software through simple examples, provide several computational benchmarks, and present a real-data example using data from the UK-Biobank, All of Us, and the HCHS/SOL cohort demonstrating how a joint analysis from multiple cohorts can be implemented without sharing individual genotype-phenotype data, and how a combined analysis can improve the prediction accuracy of PGS for Hispanics--a group severely underrepresented in GWAS data.