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Epigenome-Wide Association Study of Leukocyte Telomere Length

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Photo: Steve Horvath

In this study, the research team conducted a large-scale epigenome-wide association study of LTL using seven large cohorts the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins.

Dr. Steve Horvath from the Department of Human Genetics, David Geffen School of Medicine at the University of California Los Angeles in Los Angeles, CA 90095, USA as well as the Department of Biostatistics, Fielding School of Public Health, at the University of California Los Angeles in Los Angeles, CA 90095, USA said, "Telomeres are the (TTAGGG)n repeats located at the ends of each chromosome."

Telomere length is reported to be shorter in leukocytes of men than women, but this sex difference may depend on the measurement method.

Further, leukocyte TL is significantly but weakly associated with atherosclerotic cardiovascular disease and exhibits a complex U-shaped association with certain cancers: longer telomeres are associated with an increased risk of certain kinds of cancer.

High heritability estimates for LTL have been reported irrespective of the methods used for measuring LTL; reported heritability estimates are between 36% and 82% based on Southern blot, and between 51% and 76% based on qPCR.

Genome-wide association studies conducted in large observational cohorts have identified 11 loci associated with LTL.

Previous studies have explored the association between DNAm and LTL, but these studies were somewhat limited due to moderate sample sizes or the focus on specific regions in the genome.

The Horvath research team concluded, "We identified over 800 genome-wide significant Cp G sites that are located in or near genes with links to circadian rhythm, blood coagulation, and wound healing. These findings link two hallmarks of aging: epigenetic changes and telomere biology."

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Schedule1 Jun 2023