Determinants of telomere length across human tissues.

TitleDeterminants of telomere length across human tissues.
Publication TypeJournal Article
Year of Publication2020
AuthorsDemanelis, K, Jasmine, F, Chen, LS, Chernoff, M, Tong, L, Delgado, D, Zhang, C, Shinkle, J, Sabarinathan, M, Lin, H, Ramirez, E, Oliva, M, Kim-Hellmuth, S, Stranger, BE, Lai, T-P, Aviv, A, Ardlie, KG, Aguet, F, Ahsan, H, Doherty, JA, Kibriya, MG, Pierce, BL
Corporate AuthorsGTEx Consortium
JournalScience
Volume369
Issue6509
Date Published2020 09 11
ISSN1095-9203
KeywordsAging, Genetic Markers, Genetic Variation, Humans, Organ Specificity, Telomere, Telomere Homeostasis, Telomere Shortening
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.
DOI10.1126/science.aaz6876
Alternate JournalScience
PubMed ID32913074
PubMed Central IDPMC8108546
Grant ListR01 CA229618 / CA / NCI NIH HHS / United States
U01 MH104393 / MH / NIMH NIH HHS / United States
R01 MH107666 / MH / NIMH NIH HHS / United States
R01 MH109905 / MH / NIMH NIH HHS / United States
R01 MH106842 / MH / NIMH NIH HHS / United States
T32 GM007281 / GM / NIGMS NIH HHS / United States
K99 HG009916 / HG / NHGRI NIH HHS / United States
R01 HL142028 / HL / NHLBI NIH HHS / United States
R01 CA107431 / CA / NCI NIH HHS / United States
R01 MH090951 / MH / NIMH NIH HHS / United States
UL1 TR002550 / TR / NCATS NIH HHS / United States
U01 AG066529 / AG / NIA NIH HHS / United States
R01 HL134840 / HL / NHLBI NIH HHS / United States
R01 HG010480 / HG / NHGRI NIH HHS / United States
R01 DA006227 / DA / NIDA NIH HHS / United States
U41 HG002371 / HG / NHGRI NIH HHS / United States
R01 HG008150 / HG / NHGRI NIH HHS / United States
UM1 HG008901 / HG / NHGRI NIH HHS / United States
U01 HG007593 / HG / NHGRI NIH HHS / United States
R01 GM124486 / GM / NIGMS NIH HHS / United States
R01 MH090936 / MH / NIMH NIH HHS / United States
U01 HG007598 / HG / NHGRI NIH HHS / United States
R01 ES020506 / ES / NIEHS NIH HHS / United States
T32 DK110919 / DK / NIDDK NIH HHS / United States
R01 HG002585 / HG / NHGRI NIH HHS / United States
U01 HG007601 / HG / NHGRI NIH HHS / United States
R01 HG006855 / HG / NHGRI NIH HHS / United States
T32 HG000044 / HG / NHGRI NIH HHS / United States
P30 ES027792 / ES / NIEHS NIH HHS / United States
F32 HG009987 / HG / NHGRI NIH HHS / United States
R01 HG010067 / HG / NHGRI NIH HHS / United States
R01 MH090941 / MH / NIMH NIH HHS / United States
R01 GM122924 / GM / NIGMS NIH HHS / United States
U41 HG009494 / HG / NHGRI NIH HHS / United States
R01 MH101822 / MH / NIMH NIH HHS / United States
R35 ES028379 / ES / NIEHS NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
R01 MH090937 / MH / NIMH NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States
R35 HG010718 / HG / NHGRI NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
R01 GM108711 / GM / NIGMS NIH HHS / United States
T32 AG000243 / AG / NIA NIH HHS / United States