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

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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

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.

doi

10.1016/j.atherosclerosis.2019.10.008

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

19-26

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(19)31525-4

journal_volume

291

pub_type

杂志文章,多中心研究

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