Determinants of telomere length across human tissues

被引：354

作者：

Demanelis, Kathryn ^{[1
]}

Jasmine, Farzana ^{[1
]}

Chen, Lin S. ^{[1
]}

Chernoff, Meytal ^{[1
]}

Tong, Lin ^{[1
]}

Delgado, Dayana ^{[1
]}

Zhang, Chenan ^{[1
]}

Shinkle, Justin ^{[1
]}

Sabarinathan, Mekala ^{[1
]}

Lin, Hannah ^{[1
]}

Ramirez, Eduardo ^{[1
]}

Oliva, Meritxell ^{[1
,2
]}

Kim-Hellmuth, Sarah ^{[3
,4
,5
]}

Stranger, Barbara E. ^{[2
,6
]}

Lai, Tsung-Po ^{[7
]}

Aviv, Abraham ^{[7
]}

Ardlie, Kristin G. ^{[8
]}

Aguet, Francois ^{[8
]}

Ahsan, Habibul ^{[1
,9
,10
,11
]}

Doherty, Jennifer A. ^{[12
]}

Kibriya, Muhammad G. ^{[1
]}

Pierce, Brandon L. ^{[1
,9
,10
]}

机构：

[1] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA

[2] Univ Chicago, Ctr Data Intens Sci, Inst Genom & Syst Biol, Dept Med,Sect Genet Med, Chicago, IL USA

[3] New York Genome Ctr, New York, NY USA

[4] Max Planck Inst Psychiat, Stat Genet, Munich, Germany

[5] Columbia Univ, Dept Syst Biol, New York, NY USA

[6] Northwestern Univ, Ctr Genet Med, Feinberg Sch Med, Dept Pharmacol, Chicago, IL USA

[7] State Univ New Jersey, Ctr Human Dev & Aging, Rutgers New Jersey Med Sch, Newark, NJ USA

[8] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[9] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[10] Univ Chicago, Comprehens Canc Ctr, Chicago, IL 60637 USA

[11] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

[12] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA

来源：

SCIENCE | 2020年 / 369卷 / 6509期

基金：

瑞士国家科学基金会; 欧盟地平线“2020”;

关键词：

CANCER-RISK; DISEASE; ASSOCIATION; HEALTH; ASSAY; EPIDEMIOLOGY; MUTATIONS; FIBROSIS; SHORTEN; RTEL1;

D O I：

10.1126/science.aaz6876

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1333 / +

页数：61

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