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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.

SUBMITTER: Kuipers AL

PROVIDER: S-EPMC6899182 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Kuipers Allison L AL Wojczynski Mary K MK Barinas-Mitchell Emma E Minster Ryan L RL Wang Lihua L Feitosa Mary F MF Kulminski Alexander A Thyagarajan Bharat B Lee Joseph H JH Province Michael A MA Newman Anne B AB Zmuda Joseph M JM

Atherosclerosis 20191010

<h4>Background and aims</h4>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.<h4>Methods</h4>Participants included 2205 individuals from the Long Life Family Study (LLFS), which recruited fam ...[more]

PMID: 31634740

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Project description:BACKGROUND:The Long Life Family Study (LLFS) enrolled families exhibiting exceptional longevity. The goal of this article was to determine the prevalence and predictors of remaining independent after 7 years in the oldest generation. METHODS:We examined 7-year change in physical (free of activities of daily living difficulty), cognitive (Mini-Mental State Examination score ? 24), and overall independence (physically/cognitively independent) in adults aged 90.3 ± 6.3 from LLFS's oldest generation. Potential predictors (n = 28) of remaining independent included demographics, diseases, biomarkers, anthropometrics, and physical and cognitive performance tasks and were determined using generalized estimating equations (?: p < .05). This was a discovery/exploratory analysis, so no multiple testing correction was employed and the results require independent replication. RESULTS:At baseline (n = 1442), 67.3%, 83.8%, and 79.7% were overall, physically, and cognitively independent, respectively. After 7 years, 66% died, 7.5% were lost to follow-up, and the prevalence of overall independence decreased to 59.1% in survivors (-8.2%, 95% confidence interval: -14.1%, 2.2%). Of those with baseline independence, 156/226 (69.0%) remained independent. Predictors of remaining physically independent included younger age, better Short Physical Performance Battery score and lung function, smaller waist circumference, and lower soluble receptor for advanced glycation end-product levels (p < .05). Predictors of remaining cognitively independent included no cancer history, better Digit Symbol Substitution Test performance, and higher body weight (p < .05). CONCLUSIONS:The prevalence of independence decreased by only 8.2% after 7 years, demonstrating the close correspondence between disability and mortality. Further, despite a mean baseline age of 90 years, a large proportion of survivors remained independent, suggesting this exceptional subgroup may harbor protective mechanisms.

Dataset Information

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

Publications

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

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