Association Analysis and Meta-Analysis of Multi-Allelic Variants for Large-Scale Sequence Data.

ABSTRACT: There is great interest in understanding the impact of rare variants in human diseases using large sequence datasets. In deep sequence datasets of >10,000 samples, ~10% of the variant sites are observed to be multi-allelic. Many of the multi-allelic variants have been shown to be functional and disease-relevant. Proper analysis of multi-allelic variants is critical to the success of a sequencing study, but existing methods do not properly handle multi-allelic variants and can produce highly misleading association results. We discuss practical issues and methods to encode multi-allelic sites, conduct single-variant and gene-level association analyses, and perform meta-analysis for multi-allelic variants. We evaluated these methods through extensive simulations and the study of a large meta-

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC7288273 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature