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Prediction of telomere length and telomere attrition using a genetic risk score: The multi-ethnic study of atherosclerosis (MESA).

ABSTRACT: Background: Short telomere length (TL) and telomere attrition (TA) have been associated with age-related diseases. Objective: We assessed whether a genetic risk score for short TL (GRS-TL) combining seven TL-associated genetic variants identified in a European-ancestry genome-wide association study (GWAS) was associated with TL and TA over 10 years. Methods: Relative TL (T/S ratio) was measured by the quantitative polymerase chain reaction method for a sample of white, African American, and Hispanic participants, who attended Exam 1 and/or 5 of the Multi-Ethnic Study of Atherosclerosis (MESA). Our final sample included 1,227 participants for the TL analysis and 1,138 for the TA analysis. Participants were 45-84 years at Exam 1. We used a linear mixed effects model and adjusted for age, sex, and population structure. Models were stratified by race/ethnicity. Results: In the TL analysis, higher GRS-TL significantly predicted shorter TL (estimates = -0.18 [S.E. = 0.08], p = 0.02 for white; -0.18 [0.07], p < 0.01 for African American; and -0.13 [0.05], p = 0.02 for Hispanic) in fully adjusted models. In the TA analysis, no association between GRS-TL and TA over 10 years was found. Conclusion: Although GRS-TL was developed in European-ancestry populations, it was significantly associated with TL (but not TA) in all three race/ethnic groups examined.

SUBMITTER: Castro-Diehl C

PROVIDER: S-EPMC9592760 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Prediction of telomere length and telomere attrition using a genetic risk score: The multi-ethnic study of atherosclerosis (MESA).

Castro-Diehl Cecilia C Smith Jennifer A JA Zhao Wei W Wang Xu X Mukherjee Bhramar B Seeman Teresa T Needham Belinda L BL

Frontiers in aging 20221011

Background: Short telomere length (TL) and telomere attrition (TA) have been associated with age-related diseases. Objective: We assessed whether a genetic risk score for short TL (GRS-TL) combining seven TL-associated genetic variants identified in a European-ancestry genome-wide association study (GWAS) was associated with TL and TA over 10 years. Methods: Relative TL (T/S ratio) was measured by the quantitative polymerase chain reaction method for a sample of white, Afric ...[more]

PMID: 36304436

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Project description:BackgroundLeft ventricular (LV) circumferential strain (Ecc) is an accurate indicator of regional myocardial function, particularly using the regional Ecc or layer-specific strain.AimThis study aimed to investigate the prognostic value of a regional strain score (RSS) for predicting the incident of heart failure (HF) and coronary heart disease (CHD) in a population without a history of cardiovascular disease at baseline.Materials and methodsData from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent tagged magnetic resonance imaging for strain determination were analyzed. Using -17% and -10% as Ecc cut-offs, each segment was rated from 0 to 2 points according to the Ecc value of each layer. The endo-Ecc, mid-Ecc, and epi-Ecc values from the 16-segment model were used to calculate three RSS: Endo-, Mid-, and Epi-RSS, respectively, which were defined as a percentage of good LV regional function. The Intramyocardial-RSS was the sum of these three RSS. Cox proportional hazard models were used to evaluate the association between each RSS and incident HF and hard CHD.ResultsAmong the 1,506 participants (63.3 ± 9.4 years, 54.6% men), 122 cases of hard CHD and 91 cases of HF were observed [median (IQR) follow-up 15.9 (12.9-16.6) years]. After adjustment, Mid-, Epi-, and Intramyocardial-RSS values <50% were independently associated with HF [adjusted HR 1.43; 95% CI (1.08-2.87), p = 0.004; HR 1.80; 95% CI (1.12-3.07), p < 0.001; and HR 2.01; 95% CI (1.19-3.20), p < 0.001]. After adjustment, Endo-, Mid-, Epi-, and Intramyocardial-RSS <50% were also independently associated with hard CHD [adjusted HR 1.31; 95% CI (1.03-1.51), p = 0.04; HR 1.79; 95% CI (1.26-2.57), p < 0.001; HR 2.03; 95% CI (1.45-3.40), p < 0.001; and HR 2.28; 95% CI (1.51-3.53), p < 0.001].ConclusionsLayer-specific regional Ecc, assessed by RSS, provides a robust, independent predictive value for incident HF and hard CHD in asymptomatic participants without any history of previous clinical cardiovascular disease.Clinical trial registrationUnique identifier: NCT00005487.

Dataset Information

Prediction of telomere length and telomere attrition using a genetic risk score: The multi-ethnic study of atherosclerosis (MESA).

Publications

Prediction of telomere length and telomere attrition using a genetic risk score: The multi-ethnic study of atherosclerosis (MESA).

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