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Arterial stiffness index (ASI) is a non-invasive measure of arterial stiffness using infra-red finger sensors (photoplethysmography). It is a well-suited measure for large populations as it is relatively inexpensive to perform, and data can be acquired within seconds. These features raise interest in using ASI as a tool to estimate cardiovascular disease risk as prior work demonstrates increased arterial stiffness is associated with elevated systolic blood pressure, and ASI is predictive of cardiovascular disease and mortality. We conducted genome-wide association studies (GWASs) for ASI in 127,121 UK Biobank participants of European-ancestry. Our primary analyses identified variants at four loci reaching genome-wide significance ( P  < 5 × 10 −8 ):  TEX41  (rs1006923;  P  = 5.3 × 10 −12 ),  FOXO1  (rs7331212;  P  = 2.2 × 10 −11 ),  C1orf21  (rs1930290,  P  = 1.1 × 10 −8 ) and  MRVI1  (rs10840457,  P  = 3.4 × 10 −8 ). Gene-based testing revealed three significant genes, the most significant gene was  COL4A2  ( P  = 1.41 × 10 −8 ) encoding type IV collagen. Other candidate genes at associated loci were also involved in smooth muscle tone regulation. Our findings provide new information for understanding the development of arterial stiffness.

Genome-wide association study identifies loci for arterial stiffness index in 127,121 UK Biobank participants