TY - JOUR
T1 - Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families
AU - for the Long Life Family Study
AU - Kuipers, Allison L.
AU - Wojczynski, Mary K.
AU - Barinas-Mitchell, Emma
AU - Minster, Ryan L.
AU - Wang, Lihua
AU - Feitosa, Mary F.
AU - Kulminski, Alexander
AU - Thyagarajan, Bharat
AU - Lee, Joseph H.
AU - Province, Michael A.
AU - Newman, Anne B.
AU - Zmuda, Joseph M.
N1 - 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.
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Aging
KW - Atherosclerosis
KW - Carotid ultrasound
KW - Genome-wide study
KW - Linkage analysis
UR - http://www.scopus.com/inward/record.url?scp=85073375461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073375461&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2019.10.008
DO - 10.1016/j.atherosclerosis.2019.10.008
M3 - Article
C2 - 31634740
AN - SCOPUS:85073375461
SN - 0021-9150
VL - 291
SP - 19
EP - 26
JO - Atherosclerosis
JF - Atherosclerosis
ER -
