Our findings point to new biology as well as highlighting gene regions in systems that have previously been implicated in the genetics of BP. Several of our validated loci affect atherosclerosis or vascular remodelling (ADAMTS7, THBS2, CFDP1) and exhibit locus pleiotropy in prior genome-wide association studies for coronary artery disease or carotid intimal-media thickness24–26 (Supplementary Fig. 5a and Fig. 4). In previous work we have shown that expression of ADAMTS7 is upregulated and increases vascular smooth muscle cell migration in response to vascular injury in relation to a distinct coronary artery variant (rs3825807, not in LD with our sentinel SNV; r2 = 0.17)27. In endothelial cells ADAMTS7 encodes a metalloproteinase to cleave thrombospondin-1 encoded by THBS2 which leads to reduced endothelial cell migration and plays a role in neo-intimal repair in the vessel wall27. Our functional work indicates that the allele associated with lower DBP is also associated with lower ADAMTS7 expression in human VSMCs; this fits with the murine knockout that exhibits reduced atherosclerosis. SF3A3 encodes a splicing factor with no prior links to BP other than our reported
