Project title: Replication of GWAS signals for arterial stiffness in the ALSPAC study participants.

Outline: Stiffening of the aorta is an important independent risk factor for heart attack and stroke. It is also highly heritable but the genetics is complex, and little is currently known about the molecular pathways that bring the increase in stiffness about. In a recently completed genetic study (a GWAS) of aortic stiffness in young normotensives from the Anglo-Cardiff Collaborative Trial (ACCT), a number of genetic variants associated with aortic stiffness (pless than 10-8less than 10-6).

Aim: We specifically plan to validate 45 of these genetic variants identified in our GWAS in the ALSPAC study children who have had arterial stiffness assessments made; in particular measurements taken of their aortic pulse wave velocity (aPWV) and augmentation index during the screening.

We envisage that the findings will advance our understanding of the pathophysiology of stiffness and identify new drug targets to modulate it.