Research Paper Volume 17, Issue 2 pp 464—481
Epidemiology and genetic determination of measures of peripheral vascular health in the Long Life Family Study
- 1 Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15260, USA
- 2 Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO 63110, USA
- 3 Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA
- 4 Section of General Internal Medicine, Boston Medical Center, Boston, MA 02119, USA
- 5 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15260, USA
- 6 Division of Computational and Data Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA
- 7 Department of Computer Science and Engineering, Washington University, St. Louis, MO 63130, USA
- 8 Department of Medicine, Michigan State University, Grand Rapids, MI 49503, USA
Received: May 6, 2024 Accepted: February 3, 2025 Published: February 25, 2025
https://doi.org/10.18632/aging.206204How to Cite
Copyright: © 2025 Fricke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Peripheral artery disease (PAD) is a major contributor to morbidity in older adults. We aimed to determine genetic and non-genetic determinants of PAD and ankle-brachial index (ABI) in the Long Life Family Study (LLFS). 3006 individuals had ABI assessment, including 1090 probands (mean age 89), 1554 offspring (mean age 60) and 362 spousal controls (mean age 61). Outcomes include minimum of right and left ABIs and PAD (ABI <0.9). Stepwise regression determined independent significant non-genetic correlates of ABI and PAD. Genomewide association and linkage analyses were adjusted for age, sex, study center, significant principal components, and independent predictors. All analyses accounted for familial relatedness. Median ABI was 1.16 and 7.4% had PAD (18.2% probands, 1.0% offspring, 1.9% controls). Correlates of PAD and lower ABI included age, SBP, and creatinine (ABI only); BMI (ABI only), HDL (ABI only) and DBP (PAD only); and antihypertensive use, current smoking, female sex (ABI only), and high school noncompletion (ABI only). Genomewide linkage identified 1 region (15q12-q13) and association identified 3 single nucleotide polymorphisms (rs780213, rs12512857, rs79644420) of interest. In these families, PAD prevalence was low compared to other studies of older adults. We identified four genomic sites that may harbor variants associated with protection from PAD.
Abbreviations
ABI: Ankle Brachial Index; BMI: Body Mass Index; CVD: Cardiovascular Disease; DBP: Diastolic Blood Pressure; GWAS: Genomewide Association Study; HDL: High-Density Lipoprotein; LDL: Low-Density Lipoprotein; LLFS: Long Life Family Study; MAF: Minor Allele Frequency; mRNA: Messenger Ribonucleic Acid; NHANES: National Health and Nutrition Examination Survey; PAD: Peripheral Artery Disease; SBP: Systolic Blood Pressure; SES: Socioeconomic Status; SNP: Single Nucleotide Polymorphism.