Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families.


Journal Article

BACKGROUND AND AIMS:Atherosclerosis develops with age and is partially controlled by genetics. Research to date has identified common variants with small effects on atherosclerosis related traits. We aimed to use family-based genome-wide linkage analysis to identify chromosomal regions potentially harboring rare variants with larger effects for atherosclerosis related traits. METHODS:Participants included 2205 individuals from the Long Life Family Study (LLFS), which recruited families with exceptional longevity from Boston, New York, Pittsburgh, and Denmark. Participants underwent B-mode ultrasonography of the carotid arteries to measure intima-media thickness (IMT), inter-adventitial diameter (IAD), and plaque presence and severity. We conducted residual heritability and genome-wide linkage analyses adjusted for age, age2 , sex, and field center using pedigree-based maximum-likelihood methods in SOLAR. RESULTS:All carotid traits were significantly heritable with a range of 0.68 for IAD to 0.38 for IMT. We identified three chromosomal regions with linkage to IAD (3q13; max LOD 5.3), plaque severity (17q22-q23, max LOD 3.2), and plaque presence (17q24, max LOD 3.1). No common allelic variants within these linkage peaks were associated with the carotid artery traits. CONCLUSIONS:We identified three chromosomal regions with evidence of linkage to carotid artery diameter and atherosclerotic plaque in exceptionally long-lived families. Since common allelic variants within our linkage peaks did not account for our findings, future follow-up resequencing of these regions in LLFS families should help advance our understanding of atherosclerosis, CVD, and healthy vascular aging.

Full Text

Duke Authors

Cited Authors

  • Kuipers, AL; Wojczynski, MK; Barinas-Mitchell, E; Minster, RL; Wang, L; Feitosa, MF; Kulminski, A; Thyagarajan, B; Lee, JH; Province, MA; Newman, AB; Zmuda, JM; Long-Life Family Study,

Published Date

  • December 2019

Published In

Volume / Issue

  • 291 /

Start / End Page

  • 19 - 26

PubMed ID

  • 31634740

Pubmed Central ID

  • 31634740

Electronic International Standard Serial Number (EISSN)

  • 1879-1484

International Standard Serial Number (ISSN)

  • 0021-9150

Digital Object Identifier (DOI)

  • 10.1016/j.atherosclerosis.2019.10.008


  • eng