Jae Keith Joung

Equity Interest - Non-publicly traded entity ( e.g., stock, stock option, or other ownership interest)

Rare Sequence Variation and Diabetes Quantitative Traits

We aim to identify type 2 diabetes-quantitative trait (T2D-QT)-associated functional rare variants using WGS scans in ~3,700 white and black individuals from three cohorts in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. We will phenotype T2D-QT rare variants with existing physiological data in CHARGE, including tests for T2D risk, annotate variants using ENCODE and other resources, and confirm predicted allele-specific molecular function in vitro with appropriate experiments in appropriate cells. T2D is a growing scourge worldwide. Innovative approaches are needed to identify new molecular targets for prevention and care. Genome-wide association studies for T2D and related quantitative traits like fasting glucose have dramatically advanced molecular understanding of glycemic regulation, but the causal variant and the functional basis of associations are unclear at many loci. We propose to move T2D genetics from common variant GWAS to rare variant WGS with deep annotation and in vitro validation to generate new molecular hypotheses that advance translation of genetics into better T2D prevention and care.