Prioritizing Genes and Rare Protein-Coding Variants in Acute Myeloid Leukemia via Whole Genome Sequencing Data

Abstract

The extent to which rare and common genetic variants jointly contribute to the risk of acute myeloid leukemia (AML) still remains relatively unexplored in large-scale biobank whole-genome sequencing cohorts. Here, we leverage the latest sequencing and phenotypic data from the All of Us Research Program to identify variants, genes, and gene-sets associated with AML. We performed set-based association tests for rare protein-coding variants (Ncases=265 and Ncontrols=169,706) and single-variant association tests for common variants (Ncases=265 and Ncontrols=169,705) utilizing the large European-like ancestry sample. For the rare-variant set-based tests conducted using SAIGE-GENE+, four genes were statistically significant: DNMT3A, TET2, SRSF2, and IDH2 (Bonferroni-corrected Cauchy p-value View larger version (37K): org.highwire.dtl.DTLVardef@f37721org.highwire.dtl.DTLVardef@124212org.highwire.dtl.DTLVardef@afe432org.highwire.dtl.DTLVardef@1aec86a_HPS_FORMAT_FIGEXP M_FIG C_FIG