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  • Title: Genome-wide linkage analysis of carotid artery traits in exceptionally long-lived families.
    Author: 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.
    Journal: Atherosclerosis; 2019 Dec; 291():19-26. PubMed ID: 31634740.
    Abstract:
    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.
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