Dataset Information

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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Publications

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

Similar Datasets

Project description:BackgroundThe 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.MethodsWe 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 (α: p < .05). This was a discovery/exploratory analysis, so no multiple testing correction was employed and the results require independent replication.ResultsAt 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).ConclusionsThe 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.

Background and aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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