Rare Variant

Whole-exome sequencing of BBJ participants enabling rare variant association studies. Demonstrated expanded cancer risk profiles for BRCA1/BRCA2 pathogenic variants in the Japanese population, revealing population-specific pathogenic variant frequencies.

Whole-exome sequencing of MVP participants enabling rare variant association studies. Major pharmacogenomics initiatives leveraging the extensive VA medication records to discover genetic determinants of drug response and adverse reactions across diverse ancestries.

Series of landmark papers from TOPMed studies spanning blood pressure, lipid, pulmonary function, and glycemic trait GWAS leveraging the unique WGS data for rare variant association testing. Demonstrated value of deep WGS in diverse populations for fine-mapping and identifying causal variants. Multi-ancestry meta-analyses improved fine-mapping resolution at loci with divergent LD patterns.

Gene-based collapsing analysis in 281k participants identified 1,703 gene-phenotype associations. Rare variant contribution to common disease demonstrated.

First 49,960 WES participants released. Enables rare-coding variant association and gene-based tests.