Targeted Sequencing Study to Uncover Shared Genetic Susceptibility Between Peripheral Artery Disease and Coronary...

Area of Science:

• Cardiovascular Genetics
• Atherosclerotic Vascular Disease Research

Background:

• Peripheral artery disease (PAD) and coronary heart disease (CHD) are both manifestations of atherosclerotic vascular disease.
• The extent of shared genetic susceptibility between PAD and CHD remains unclear.

Purpose of the Study:

• To investigate whether genetic susceptibility variants associated with CHD are also associated with PAD.
• To identify common and low-frequency/rare variants contributing to shared genetic risk.

Main Methods:

• Targeted sequencing of 41 genomic regions previously associated with CHD in genome-wide association studies.
• Analysis of 1749 PAD cases and 1855 controls of European ancestry.
• Association testing for common variants and gene-level analyses for low-frequency/rare variants using sequence kernel association test and permutation test.

Main Results:

• Common variants in SH2B3, ABO, and ZEB2 were significantly associated with PAD after Bonferroni correction (P<4.5×10^-5).
• Gene-level analyses revealed the strongest associations for LPL and SH2B3.
• These findings highlight shared genetic underpinnings between CHD and PAD.

Conclusions:

• Targeted sequencing of CHD-associated genomic regions identified common variants and genes associated with PAD.
• This research elucidates the shared genetic susceptibility between coronary heart disease and peripheral artery disease.
• The study provides insights into the genetic basis of atherosclerotic vascular disease manifestations.