Abstract 008: Genetic Studies Identify A Novel Role Of CCDC93 In Arterial Relaxation And Central Systolic Blood Pressure

Previous genome-wide association studies (GWAS) have identified and validated variants at more than 1000 loci with modest effects on population blood pressure (BP), explaining in aggregate ~6% of the trait variance and highlighting genetic differences in BP regulation in ethnically diverse populations. We performed an exome-wide association study (EWAS) in Han Chinese population (N=5,954) from Beijing and identified 4 EWAS single nucleotide polymorphism (SNP)-trait associations with 3 SNPs, including two novel associations (rs2165468-peripheral systolic BP and rs33975708-central systolic BP (cSBP). rs33975708 is a coding variant in the coiled-coil domain containing 93 ( CCDC93 ) gene, c.535C>T, p.Arg179Cys (MAF=0.15%) and was associated with substantially increased cSBP (β=29.3 mmHg, P =1.23E-7) in Han Chinese population. CRISPR/Cas9 was used to introduce this variant in mice to investigate vascular molecular mechanisms. While this did not yield a viable mouse with the specific SNP, we did generate mice with an out of frame deletion making a gene knock-out. Ccdc93 deletion ( Ccdc93 -/- ) in its homozygous form was embryonic lethal (更多