Determinants of telomere length across human tissues

Author:

Demanelis Kathryn1ORCID,Jasmine Farzana1,Chen Lin S.1,Chernoff Meytal1ORCID,Tong Lin1ORCID,Delgado Dayana1,Zhang Chenan1ORCID,Shinkle Justin1,Sabarinathan Mekala1ORCID,Lin Hannah1ORCID,Ramirez Eduardo1ORCID,Oliva Meritxell12ORCID,Kim-Hellmuth Sarah345ORCID,Stranger Barbara E.26ORCID,Lai Tsung-Po7ORCID,Aviv Abraham7ORCID,Ardlie Kristin G.8ORCID,Aguet François8ORCID,Ahsan Habibul191011,Doherty Jennifer A.12ORCID,Kibriya Muhammad G.1ORCID,Pierce Brandon L.1910ORCID,

Affiliation:

1. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.

2. Section of Genetic Medicine, Department of Medicine, Institute for Genomics and Systems Biology, Center for Data Intensive Science, University of Chicago, Chicago, IL, USA.

3. New York Genome Center, New York, NY, USA.

4. Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.

5. Department of Systems Biology, Columbia University, New York, NY, USA.

6. Center for Genetic Medicine, Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

7. Center of Human Development and Aging, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, USA.

8. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

9. Department of Human Genetics, University of Chicago, Chicago, IL, USA.

10. University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.

11. Department of Medicine, University of Chicago, Chicago, IL, USA.

12. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Abstract

Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in nonblood, disease-relevant tissue types. Here, we characterize variability in TLs from 6391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation affects TL in multiple tissue types and that TL may mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.

Funder

National Institute on Aging

National Human Genome Research Institute

National Cancer Institute

National Institute of Environmental Health Sciences

Marie-Skłodowska Curie Fellowship H2020 Grant

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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