Genome-wide association study identifies loci for arterial stiffness index in 127,121 UK Biobank participants.
Kenneth FungJulia RamírezHelen R WarrenNay AungAaron M LeeEvan TzanisSteffen Erhard PetersenPatricia B MunroePublished in: Scientific reports (2019)
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.
Keyphrases
- genome wide
- blood pressure
- genome wide association study
- copy number
- cardiovascular disease
- dna methylation
- genome wide association
- heart rate
- smooth muscle
- hypertensive patients
- cardiovascular events
- big data
- signaling pathway
- left ventricular
- gene expression
- healthcare
- transcription factor
- adipose tissue
- heart failure
- cardiovascular risk factors
- genome wide identification
- pi k akt
- risk factors
- cell proliferation
- weight loss
- skeletal muscle
- metabolic syndrome