AUTHOR=Castro-Diehl Cecilia , Smith Jennifer A. , Zhao Wei , Wang Xu , Mukherjee Bhramar , Seeman Teresa , Needham Belinda L. 

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

JOURNAL=Frontiers in Aging

VOLUME=3

YEAR=2022

URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.1021051

DOI=10.3389/fragi.2022.1021051

ISSN=2673-6217

ABSTRACT=<p><bold>Background:</bold> Short telomere length (TL) and telomere attrition (TA) have been associated with age-related diseases.</p><p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> In the TL analysis, higher GRS-TL significantly predicted shorter TL (estimates = -0.18 [S.E. = 0.08], <italic>p</italic> = 0.02 for white; -0.18 [0.07], <italic>p</italic> &lt; 0.01 for African American; and -0.13 [0.05], <italic>p</italic> = 0.02 for Hispanic) in fully adjusted models. In the TA analysis, no association between GRS-TL and TA over 10 years was found.</p><p><bold>Conclusion:</bold> 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.</p>