Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families
Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families
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DOI：
10.1016/j.atherosclerosis.2019.10.008
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发表时间：
2019-12-01
期刊：
影响因子：
5.3
通讯作者：
Zmuda, Joseph M.
中科院分区：
文献类型：
--
作者：
Kuipers, Allison L.;Wojczynski, Mary K.;Zmuda, Joseph M.
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, age(2), 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.
