Faculty Collaboration Database

Targeted Sequencing Study to Uncover Shared Genetic Susceptibility Between Peripheral Artery Disease and Coronary Heart Disease-Brief Report. Arterioscler Thromb Vasc Biol 2019 Jun;39(6):1227-1233

Date

05/10/2019

Pubmed ID

31070467

Pubmed Central ID

PMC6531315

DOI

10.1161/ATVBAHA.118.312128

Scopus ID

2-s2.0-85066509886 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

Objective- It is unclear to what extent genetic susceptibility variants are shared between peripheral artery disease (PAD) and coronary heart disease (CHD), both manifestations of atherosclerotic vascular disease. We investigated whether common and low-frequency/rare variants in loci associated with CHD are also associated with PAD. Approach and Results- Targeted sequencing of 41 genomic regions associated with CHD in genome-wide association studies was performed in 1749 PAD cases (65±11 years, 61% men) and 1855 controls (60±11 years, 56% men) of European ancestry. PAD cases had a resting/postexercise ankle-brachial index ≤0.9, or history of lower extremity revascularization; controls had no history of PAD. We tested the association of common (defined as minor allele frequency ≥5%) variants with PAD assuming an additive genetic model with adjustment for age and sex. To identify low-frequency/rare variants (minor allele frequency <5%) associated with PAD, we conducted gene-level analyses using sequence kernel association test and permutation test. After Bonferroni correction, we found common variants in SH2B3, ABO, and ZEB2 to be associated with PAD ( P<4.5×10^-5). At the gene level, the strongest associations were for LPL and SH2B3. Conclusions- Targeted sequencing of 41 genomic regions associated with CHD revealed several common variants/genes to be associated with PAD, highlighting the basis of shared genetic susceptibility between CHD and PAD.

Author List

Safarova MS, Fan X, Austin EE, van Zuydam N, Hopewell J, Schaid DJ, Kullo IJ

Author

Maya S. Safarova MD, PhD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Case-Control Studies
Coronary Disease
Female
Gene Frequency
Genetic Association Studies
Genetic Loci
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
Middle Aged
Peripheral Arterial Disease
Phenotype
Risk Factors
Sequence Analysis, DNA