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

for the Long Life Family Study

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
StatePublished - Dec 2019

Bibliographical note

Funding Information:
The LLFS was supported by the National Institute on Aging ( U01AG023712 , U01AG023744 , U01AG023746 , U01AG023749 , and U01AG023755 ). Dr. Kuipers was supported by grant K01HL125658 (PI: Kuipers) from the National Heart, Lung and Blood Institute .

Publisher Copyright:
© 2019 Elsevier B.V.


  • Aging
  • Atherosclerosis
  • Carotid ultrasound
  • Genome-wide study
  • Linkage analysis

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