Investigate fetal-specific cardiac regulatory variants and their overlap with cardiac GWAS lead variants

We have derived iPSC-CVPCs from 180 individuals and showed that their transcriptomes are more similar to fetal heart than to adult cardiac tissues. Our goal is to leverage these data in combination with WGS to perform eQTL analyses. We plan to assess whether fetal-specific eQTLs are associated with complex adult cardiac traits, by colocalizing eQTLs with summary statistics from GWAS (cardiac traits.) Our preliminary analyses show that eQTLs in iPSC-CVPCs identifies cardiac disease GWAS variants that are active in the fetal but not adult heart, indicating that they play a role in development. Our findings provide genetic evidence supporting the fetal origins of the cardiovascular disease hypothesis and highlight the importance of investigating genetic associations across stages of development (i.e. fetal and adult tissues) to fully understand the genetic underpinnings of complex traits and disease. We are looking for rotation students to conduct QTL analyses using large ATAC-seq and ChiP-seq for H3K27ac datasets generated from the iPSC-CVPCs.