1) Common genetic variants have recently been identified through the aggregation of GWAS in large sample size, but in total these variants explain a small fraction of the heritable contribution to BP variation. For further investigation of variants associated with BP variation SardiNIA study has joined new IGCBP consortium using meta-analysis of CardioMetaboChip and IGCBP GWAS. To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 1 40,886 individuals were used for validation. We identified 66 blood pressureassociated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressurerelated pathways and highlight tissues beyond the classical renal system in blood pressure regulation. 2) We found evidence that reduced nighttime blood pressure dipping is associated with antagonism and impulsivity-related traits but not with measures of emotional vulnerability. The strongest associations were found with conscientiousness, a trait that may have a broad impact on cardiovascular health. 3) We report the identification of 52 genomic loci, of which 32 are novel, reliably associated with one or more QRS phenotypes at P<110-8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding suggesting that they represent regions of the genome that are actively transcribed in the human heart.
Showing the most recent 10 out of 28 publications
