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

Publication ,  Journal Article
Kuipers, AL; Wojczynski, MK; Barinas-Mitchell, E; Minster, RL; Wang, L; Feitosa, MF; Kulminski, A; Thyagarajan, B; Lee, JH; Province, MA ...
Published in: Atherosclerosis
December 2019

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.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.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.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.

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Published In

Atherosclerosis

DOI

EISSN

1879-1484

ISSN

0021-9150

Publication Date

December 2019

Volume

291

Start / End Page

19 / 26

Related Subject Headings

  • United States
  • Severity of Illness Index
  • Risk Factors
  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Plaque, Atherosclerotic
  • Phenotype
  • Pedigree
  • Middle Aged
  • Male
 

Citation

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Kuipers, A. L., Wojczynski, M. K., Barinas-Mitchell, E., Minster, R. L., Wang, L., Feitosa, M. F., … Long-Life Family Study, . (2019). Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families. Atherosclerosis, 291, 19–26. https://doi.org/10.1016/j.atherosclerosis.2019.10.008
Kuipers, Allison L., Mary K. Wojczynski, Emma Barinas-Mitchell, Ryan L. Minster, Lihua Wang, Mary F. Feitosa, Alexander Kulminski, et al. “Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families.Atherosclerosis 291 (December 2019): 19–26. https://doi.org/10.1016/j.atherosclerosis.2019.10.008.
Kuipers AL, Wojczynski MK, Barinas-Mitchell E, Minster RL, Wang L, Feitosa MF, et al. Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families. Atherosclerosis. 2019 Dec;291:19–26.
Kuipers, Allison L., et al. “Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families.Atherosclerosis, vol. 291, Dec. 2019, pp. 19–26. Epmc, doi:10.1016/j.atherosclerosis.2019.10.008.
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. Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families. Atherosclerosis. 2019 Dec;291:19–26.
Journal cover image

Published In

Atherosclerosis

DOI

EISSN

1879-1484

ISSN

0021-9150

Publication Date

December 2019

Volume

291

Start / End Page

19 / 26

Related Subject Headings

  • United States
  • Severity of Illness Index
  • Risk Factors
  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Plaque, Atherosclerotic
  • Phenotype
  • Pedigree
  • Middle Aged
  • Male