Telomere length measurement as a clinical biomarker of aging and disease

References

• Reddel RR. Telomere maintenance mechanisms in cancer: clinical implications. CPD. 2014;20:6361–6374.
   Google Scholar
• Allsopp RC, Vaziri H, Patterson C, et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA. 1992;89:10114–10118.
   PubMed Web of Science ®Google Scholar
• Verdun RE, Crabbe L, Haggblom C, et al. Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol Cell. 2005;20:551–561.
   PubMed Web of Science ®Google Scholar
• Ramirez R, Carracedo J, Jimenez R, et al. Massive telomere loss is an early event of DNA damage-induced apoptosis. J Biol Chem. 2003;278:836–842.
   PubMed Web of Science ®Google Scholar
• Andrews NP, Fujii H, Goronzy JJ, et al. Telomeres and immunological diseases of aging. Gerontology. 2010;56:390–403.
   PubMed Web of Science ®Google Scholar
• Costenbader KH, Prescott J, Zee RY, et al. Immunosenescence and rheumatoid arthritis: does telomere shortening predict impending disease? Autoimmun Rev. 2011;10:569–573.
   PubMed Web of Science ®Google Scholar
• Kordinas V, Ioannidis A, Chatzipanagiotou S. The telomere/telomerase system in chronic inflammatory diseases. Cause or effect? Genes (Basel). 2016;7:60.
   PubMed Web of Science ®Google Scholar
• Broer L, Codd V, Nyholt DR, et al. Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur J Hum Genet. 2013;21:1163–1168.
   PubMed Web of Science ®Google Scholar
• Savage SA, Alter BP. Dyskeratosis congenita. Hematol Oncol Clin North Am. 2009;23:215–231.
   PubMed Web of Science ®Google Scholar
• Alter BP, Baerlocher GM, Savage SA, et al. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood. 2007;110:1439–1447.
   PubMed Web of Science ®Google Scholar
• Armanios M, Blackburn EH. The telomere syndromes. Nat Rev Genet. 2012;13:693–704.
   PubMed Web of Science ®Google Scholar
• Nordfjall K, Larefalk A, Lindgren P, et al. Telomere length and heredity: indications of paternal inheritance. Proc Natl Acad Sci USA. 2005;102:16374–16378.
   PubMed Web of Science ®Google Scholar
• Nordfjall K, Svenson U, Norrback KF, et al. Large-scale parent-child comparison confirms a strong paternal influence on telomere length. Eur J Hum Genet. 2010;18:385–389.
   PubMed Web of Science ®Google Scholar
• Njajou OT, Cawthon RM, Damcott CM, et al. Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci USA. 2007;104:12135–12139.
   PubMed Web of Science ®Google Scholar
• Arai Y, Martin-Ruiz CM, Takayama M, et al. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine. 2015;2:1549–1558.
   PubMed Web of Science ®Google Scholar
• Chiang YJ, Calado RT, Hathcock KS, et al. Telomere length is inherited with resetting of the telomere set-point. Proc Natl Acad Sci USA. 2010;107:10148–10153.
   PubMed Web of Science ®Google Scholar
• De Meyer T, Rietzschel ER, De Buyzere ML, et al. Paternal age at birth is an important determinant of offspring telomere length. Hum Mol Genet. 2007;16:3097–3102.
   PubMed Web of Science ®Google Scholar
• Kimura M, Cherkas LF, Kato BS, et al. Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet. 2008;4:e37
   PubMed Web of Science ®Google Scholar
• Hjelmborg JB, Dalgard C, Mangino M, et al. Paternal age and telomere length in twins: the germ stem cell selection paradigm. Aging Cell. 2015;14:701–703.
   PubMed Web of Science ®Google Scholar
• Factor-Litvak P, Susser E, Kezios K, et al. Leukocyte telomere length in newborns: implications for the role of telomeres in human disease. Pediatrics. 2016;137:e20153927.
   PubMed Web of Science ®Google Scholar
• Lin J, Epel E, Blackburn E. Telomeres and lifestyle factors: roles in cellular aging. Mutat Res. 2012;730:85–89.
   PubMed Web of Science ®Google Scholar
• Entringer S, Epel ES, Kumsta R, et al. Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proc Natl Acad Sci USA. 2011;108:E513–E518.
   PubMed Web of Science ®Google Scholar
• Pickett HA, Reddel RR. The role of telomere trimming in normal telomere length dynamics. Cell Cycle. 2012;11:1309–1315.
   PubMed Web of Science ®Google Scholar
• Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–334.
   PubMed Web of Science ®Google Scholar
• Chan SS, Chang S. Defending the end zone: studying the players involved in protecting chromosome ends. FEBS Lett. 2010;584:3773–3778.
   PubMed Web of Science ®Google Scholar
• Miyake Y, Nakamura M, Nabetani A, et al. RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell. 2009;36:193–206.
   PubMed Web of Science ®Google Scholar
• Chen LY, Redon S, Lingner J. The human CST complex is a terminator of telomerase activity. Nature. 2012;488:540–544.
   PubMed Web of Science ®Google Scholar
• Halliwell B, Aruoma OI. DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 1991;281:9–19.
   PubMed Web of Science ®Google Scholar
• Cote HC, Soudeyns H, Thorne A, et al. Leukocyte telomere length in HIV-infected and HIV-exposed uninfected children: shorter telomeres with uncontrolled HIV viremia. PLoS One. 2012;7:e39266.
   PubMed Web of Science ®Google Scholar
• Zanet DL, Thorne A, Singer J, et al. Association between short leukocyte telomere length and HIV infection in a cohort study: no evidence of a relationship with antiretroviral therapy. Clin Infect Dis. 2014;58:1322–1332.
   PubMed Web of Science ®Google Scholar
• van de Berg PJ, Griffiths SJ, Yong SL, et al. Cytomegalovirus infection reduces telomere length of the circulating T cell pool. J Immunol. 2010;184:3417–3423.
   PubMed Web of Science ®Google Scholar
• Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature. 1989;337:331–337.
   PubMed Web of Science ®Google Scholar
• Schmidt JC, Cech TR. Human telomerase: biogenesis, trafficking, recruitment, and activation. Genes Dev. 2015;29:1095–1105.
   PubMed Web of Science ®Google Scholar
• Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science. 2015;350:1193–1198.
   PubMed Web of Science ®Google Scholar
• Vannier JB, Pavicic-Kaltenbrunner V, Petalcorin MI, et al. RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell. 2012;149:795–806.
   PubMed Web of Science ®Google Scholar
• Pickett HA, Cesare AJ, Johnston RL, et al. Control of telomere length by a trimming mechanism that involves generation of t-circles. Embo J. 2009;28:799–809.
   PubMed Web of Science ®Google Scholar
• Pickett HA, Henson JD, Au AY, et al. Normal mammalian cells negatively regulate telomere length by telomere trimming. Hum Mol Genet. 2011;20:4684–4692.
   PubMed Web of Science ®Google Scholar
• Rivera T, Haggblom C, Cosconati S, et al. A balance between elongation and trimming regulates telomere stability in stem cells. Nat Struct Mol Biol. 2017;24:30–39.
   PubMed Web of Science ®Google Scholar
• Gadalla SM, Wang T, Haagenson M, et al. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia. JAMA. 2015;313:594–602.
   PubMed Web of Science ®Google Scholar
• Bojesen SE, Pooley KA, Johnatty SE, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013;45:371–384. 384e371-372.
   PubMed Web of Science ®Google Scholar
• Walsh KM, Codd V, Smirnov IV, et al. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat Genet. 2014;46:731–735.
   PubMed Web of Science ®Google Scholar
• Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000;21:361–370.
   PubMed Web of Science ®Google Scholar
• Petersen S, Saretzki G, von Zglinicki T. Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Exp Cell Res. 1998;239:152–160.
   PubMed Web of Science ®Google Scholar
• Oikawa S, Kawanishi S. Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett. 1999;453:365–368.
   PubMed Web of Science ®Google Scholar
• Opresko PL, Fan J, Danzy S, et al. 3rd, Bohr VA. Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2. Nucleic Acids Res. 2005;33:1230–1239.,
   PubMed Web of Science ®Google Scholar
• Madjid M, Fatemi O. Components of the complete blood count as risk predictors for coronary heart disease: in-depth review and update. Tex Heart Inst J. 2013;40:17–29.
   PubMed Web of Science ®Google Scholar
• Mittal M, Siddiqui MR, Tran K, et al. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20:1126–1167.
   PubMed Web of Science ®Google Scholar
• Demissie S, Levy D, Benjamin EJ, et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell. 2006;5:325–330.
   PubMed Web of Science ®Google Scholar
• Doulatov S, Notta F, Laurenti E, et al. Hematopoiesis: a human perspective. Cell Stem Cell. 2012;10:120–136.
   PubMed Web of Science ®Google Scholar
• Rufer N, Brummendorf TH, Kolvraa S, et al. Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med. 1999;190:157–167.
   PubMed Web of Science ®Google Scholar
• Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30:e47
   PubMed Web of Science ®Google Scholar
• Cawthon RM. Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res. 2009;37:e21
   PubMed Web of Science ®Google Scholar
• Canela A, Vera E, Klatt P, et al. High-throughput telomere length quantification by FISH and its application to human population studies. Proc Natl Acad Sci USA. 2007;104:5300–5305.
   PubMed Web of Science ®Google Scholar
• Poon SS, Martens UM, Ward RK, et al. Telomere length measurements using digital fluorescence microscopy. Cytometry. 1999;36:267–278.
   PubMedGoogle Scholar
• Kimura M, Stone RC, Hunt SC, et al. Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths. Nat Protoc. 2010;5:1596–1607.
   PubMed Web of Science ®Google Scholar
• Baird DM, Rowson J, Wynford-Thomas D, et al. Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat Genet. 2003;33:203–207.
   PubMed Web of Science ®Google Scholar
• Aubert G, Hills M, Lansdorp PM. Telomere length measurement-caveats and a critical assessment of the available technologies and tools. Mutat Res. 2012;730:59–67.
   PubMed Web of Science ®Google Scholar
• Lai TP, Wright WE, Shay JW. Comparison of telomere length measurement methods. Phil Trans R Soc B. 2018;373:20160451.
   PubMed Web of Science ®Google Scholar
• Sanders JL, Newman AB. Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol Rev. 2013;35:112–131.
   PubMed Web of Science ®Google Scholar
• Bojesen SE. Telomeres and human health. J Intern Med. 2013;274:399–413.
   PubMed Web of Science ®Google Scholar
• Martin-Ruiz CM, Baird D, Roger L, et al. Reproducibility of Telomere Length Assessment–An International Collaborative Study. Int J Epidemiol. 2015;44:1749–1754.
   PubMed Web of Science ®Google Scholar
• Mangino M, Hwang SJ, Spector TD, et al. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet. 2012;21:5385–5394.
   PubMed Web of Science ®Google Scholar
• Howden LMaJAM. Age and Sex Composition: 2010. In: Bureau USC, ed. Washington, D.C.: U. S. Census Bureau; 2011.
   Google Scholar
• Deelen J, Beekman M, Codd V, et al. Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers. Int J Epidemiol. 2014;43:878–886.
   PubMed Web of Science ®Google Scholar
• Lapham K, Kvale MN, Lin J, et al. Automated assay of telomere length measurement and informatics for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort. Genetics. 2015;200:1061–1072.
   PubMed Web of Science ®Google Scholar
• Rode L, Nordestgaard BG, Bojesen SE. Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population. J Natl Cancer Inst. 2015;107:djv074
   PubMedGoogle Scholar
• Weischer M, Bojesen SE, Nordestgaard BG. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart. PLoS Genet. 2014;10:e1004191.
   PubMed Web of Science ®Google Scholar
• Mons U, Muezzinler A, Schottker B, et al. Leukocyte telomere length and all-cause, cardiovascular disease, and cancer mortality: results from individual-participant-data meta-analysis of 2 large prospective cohort studies. Am J Epidemiol. 2017;185:1317–1326.
   PubMed Web of Science ®Google Scholar
• Needham BL, Rehkopf D, Adler N, et al. Leukocyte telomere length and mortality in the National Health and Nutrition Examination Survey, 1999-2002. Epidemiology. 2015;26:528–535.
   PubMed Web of Science ®Google Scholar
• Goglin SE, Farzaneh-Far R, Epel ES, et al. Change in leukocyte telomere length predicts mortality in patients with stable coronary heart disease from the Heart and Soul Study. PLoS One. 2016;11:e0168868.
   PubMed Web of Science ®Google Scholar
• Farzaneh-Far R, Cawthon RM, Na B, et al. Prognostic value of leukocyte telomere length in patients with stable coronary artery disease: data from the Heart and Soul Study. Arterioscler Thromb Vasc Biol. 2008;28:1379–1384.
   PubMed Web of Science ®Google Scholar
• Houben JM, Giltay EJ, Rius-Ottenheim N, et al. Telomere length and mortality in elderly men: the Zutphen Elderly Study. J Gerontol A Biol Sci Med Sci. 2011;66:38–44.
   PubMed Web of Science ®Google Scholar
• Svensson J, Karlsson MK, Ljunggren O, et al. Leukocyte telomere length is not associated with mortality in older men. Exp Gerontol. 2014;57:6–12.
   PubMed Web of Science ®Google Scholar
• Marioni RE, Harris SE, Shah S, et al. The epigenetic clock and telomere length are independently associated with chronological age and mortality. Int J Epidemiol. 2016;45:424–432.
   PubMed Web of Science ®Google Scholar
• Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135:e146–e603.
   PubMed Web of Science ®Google Scholar
• Bezzina CR, Lahrouchi N, Priori SG. Genetics of sudden cardiac death. Circ Res. 2015;116:1919–1936.
   PubMed Web of Science ®Google Scholar
• Yang KC, Kyle JW, Makielski JC, et al. Mechanisms of sudden cardiac death: oxidants and metabolism. Circ Res. 2015;116:1937–1955.
   PubMed Web of Science ®Google Scholar
• Wellens HJ, Schwartz PJ, Lindemans FW, et al. Risk stratification for sudden cardiac death: current status and challenges for the future. Eur Heart J. 2014;35:1642–1651.
   PubMed Web of Science ®Google Scholar
• Hayashi M, Shimizu W, Albert CM. The spectrum of epidemiology underlying sudden cardiac death. Circ Res. 2015;116:1887–1906.
   PubMed Web of Science ®Google Scholar
• Wilson PW, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–1847.
   PubMed Web of Science ®Google Scholar
• Brouilette S, Singh RK, Thompson JR, et al. White cell telomere length and risk of premature myocardial infarction. Arterioscler Thromb Vasc Biol. 2003;23:842–846.
   PubMed Web of Science ®Google Scholar
• Brouilette SW, Moore JS, McMahon AD, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet. 2007;369:107–114.
   PubMed Web of Science ®Google Scholar
• Stone NJ, Robinson JG, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;2014:S1–S45.
   Google Scholar
• Hammadah M, Al Mheid I, Wilmot K, et al. Telomere shortening, regenerative capacity, and cardiovascular outcomes. Circ Res. 2017;120:1130–1138.
   PubMed Web of Science ®Google Scholar
• Fitzpatrick AL, Kronmal RA, Gardner JP, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol. 2007;165:14–21.
   PubMed Web of Science ®Google Scholar
• D'Mello MJJ, Ross SA, Anand SS, et al. Telomere Length and Risk of Myocardial Infarction in a MultiEthnic Population: The INTERHEART Study. J Am Coll Cardiol. 2016;67:1863–1865.
   PubMedGoogle Scholar
• Scheller Madrid A, Rode L, Nordestgaard BG, et al. Short Telomere Length and Ischemic Heart Disease: Observational and Genetic Studies in 290 022 Individuals. Clin Chem. 2016;62:1140–1149.
   PubMed Web of Science ®Google Scholar
• Willeit P, Willeit J, Mayr A, et al. Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010;304:69–75.
   PubMed Web of Science ®Google Scholar
• Peters SA, den Ruijter HM, Bots ML, et al. Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: a systematic review. Heart. 2012;98:177–184.
   PubMed Web of Science ®Google Scholar
• Raschenberger J, Kollerits B, Hammerer-Lercher A, et al. The association of relative telomere length with symptomatic peripheral arterial disease: results from the CAVASIC study. Atherosclerosis. 2013;229:469–474.
   PubMed Web of Science ®Google Scholar
• Mainous AG, 3rd, Codd V, Diaz VA, et al. Leukocyte telomere length and coronary artery calcification. Atherosclerosis. 2010;210:262–267.
   PubMed Web of Science ®Google Scholar
• Hunt SC, Kimura M, Hopkins PN, et al. Leukocyte telomere length and coronary artery calcium. Am J Cardiol. 2015;116:214–218.
   PubMed Web of Science ®Google Scholar
• Rask-Madsen C, Kahn CR. Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2012;32:2052–2059.
   PubMed Web of Science ®Google Scholar
• Goldsworthy ME, Potter PK. Modelling age-related metabolic disorders in the mouse. Mamm Genome. 2014;25:487–496.
   PubMed Web of Science ®Google Scholar
• Abel ED, O'Shea KM, Ramasamy R. Insulin resistance: metabolic mechanisms and consequences in the heart. Arterioscler Thromb Vasc Biol. 2012;32:2068–2076.
   PubMed Web of Science ®Google Scholar
• Willeit P, Raschenberger J, Heydon EE, et al. Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis. PLoS One. 2014;9:e112483.
   PubMed Web of Science ®Google Scholar
• Zhao J, Zhu Y, Lin J, et al. Short leukocyte telomere length predicts risk of diabetes in American Indians: the strong heart family study. Diabetes. 2014;63:354–362.
   PubMed Web of Science ®Google Scholar
• Xiao F, Zheng X, Cui M, et al. Telomere dysfunction-related serological markers are associated with type 2 diabetes. Diabetes Care. 2011;34:2273–2278.
   PubMed Web of Science ®Google Scholar
• Menke A, Casagrande S, Cowie CC. Leukocyte telomere length and diabetes status, duration, and control: the 1999-2002 National Health and Nutrition Examination Survey. BMC Endocr Disord. 2015;15:52.
   PubMed Web of Science ®Google Scholar
• Bonfigli AR, Spazzafumo L, Prattichizzo F, et al. Leukocyte telomere length and mortality risk in patients with type 2 diabetes. Oncotarget. 2016;7:50835–50844.
   PubMedGoogle Scholar
• Astrup AS, Tarnow L, Jorsal A, et al. Telomere length predicts all-cause mortality in patients with type 1 diabetes. Diabetologia. 2010;53:45–48.
   PubMed Web of Science ®Google Scholar
• Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Statist Med. 2008;27:1133–1163.
   PubMed Web of Science ®Google Scholar
• Thomas DC, Conti DV. Commentary: the concept of 'Mendelian Randomization'. Int J Epidemiol. 2004;33:21–25.
   PubMed Web of Science ®Google Scholar
• Didelez V, Sheehan N. Mendelian randomization as an instrumental variable approach to causal inference. Stat Methods Med Res. 2007;16:309–330.
   PubMed Web of Science ®Google Scholar
• Codd V, Nelson CP, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet. 2013;45:422–427.
   PubMed Web of Science ®Google Scholar
• Pooley KA, Bojesen SE, Weischer M, et al. A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk. Hum Mol Genet. 2013;22:5056–5064.
   PubMed Web of Science ®Google Scholar
• Codd V, Mangino M, van der Harst P, et al. Common variants near TERC are associated with mean telomere length. Nat Genet. 2010;42:197–199.
   PubMed Web of Science ®Google Scholar
• Levy D, Neuhausen SL, Hunt SC, et al. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc Natl Acad Sci USA. 2010;107:9293–9298.
   PubMed Web of Science ®Google Scholar
• Prescott J, Kraft P, Chasman DI, et al. Genome-wide association study of relative telomere length. PLoS One. 2011;6:e19635
   PubMed Web of Science ®Google Scholar
• Lee JH, Cheng R, Honig LS, et al. Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study. Front Genet. 2014;4:310.
   PubMed Web of Science ®Google Scholar
• Maubaret CG, Salpea KD, Romanoski CE, et al. Association of TERC and OBFC1 haplotypes with mean leukocyte telomere length and risk for coronary heart disease. PLoS One. 2013;8:e83122
   PubMed Web of Science ®Google Scholar
• van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature. 1997;385:740–743.
   PubMed Web of Science ®Google Scholar
• Smogorzewska A, van Steensel B, Bianchi A, et al. Control of human telomere length by TRF1 and TRF2. Mol Cell Biol. 2000;20:1659–1668.
   PubMed Web of Science ®Google Scholar
• Ye JZ, Donigian JR, van Overbeek M, et al. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J Biol Chem. 2004;279:47264–47271.
   PubMed Web of Science ®Google Scholar
• Takai KK, Kibe T, Donigian JR, et al. Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell. 2011;44:647–659.
   PubMed Web of Science ®Google Scholar
• Nandakumar J, Cech TR. Finding the end: recruitment of telomerase to telomeres. Nat Rev Mol Cell Biol. 2013;14:69–82.
   PubMed Web of Science ®Google Scholar
• Sexton AN, Regalado SG, Lai CS, et al. Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation. Genes Dev. 2014;28:1885–1899.
   PubMed Web of Science ®Google Scholar
• Rai R, Chen Y, Lei M, et al. TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Nat Comms. 2016;7:10881.
   PubMed Web of Science ®Google Scholar
• Savage SA, Giri N, Baerlocher GM, et al. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet. 2008;82:501–509.
   PubMed Web of Science ®Google Scholar
• Walne AJ, Vulliamy T, Beswick R, et al. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood. 2008;112:3594–3600.
   PubMed Web of Science ®Google Scholar
• Kocak H, Ballew BJ, Bisht K, et al. Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1. Genes Dev. 2014;28:2090–2102.
   PubMed Web of Science ®Google Scholar
• Guo Y, Kartawinata M, Li J, et al. Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1. Blood. 2014;124:2767–2774.
   PubMed Web of Science ®Google Scholar
• Karlseder J, Kachatrian L, Takai H, et al. Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol Cell Biol. 2003;23:6533–6541.
   PubMed Web of Science ®Google Scholar
• Celli GB, de Lange T. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol. 2005;7:712–718.
   PubMed Web of Science ®Google Scholar
• Chiang YJ, Kim SH, Tessarollo L, et al. Telomere-associated protein TIN2 is essential for early embryonic development through a telomerase-independent pathway. Mol Cell Biol. 2004;24:6631–6634.
   PubMed Web of Science ®Google Scholar
• Kibe T, Osawa GA, Keegan CE, et al. Telomere protection by TPP1 is mediated by POT1a and POT1b. Mol Cell Biol. 2010;30:1059–1066.
   PubMed Web of Science ®Google Scholar
• Hockemeyer D, Daniels JP, Takai H, et al. Recent expansion of the telomeric complex in rodents: two distinct POT1 proteins protect mouse telomeres. Cell. 2006;126:63–77.
   PubMed Web of Science ®Google Scholar
• Robles-Espinoza CD, Harland M, Ramsay AJ, et al. POT1 loss-of-function variants predispose to familial melanoma. Nat Genet. 2014;46:478–481.
   PubMed Web of Science ®Google Scholar
• Speedy HE, Kinnersley B, Chubb D, et al. Germ line mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia. Blood. 2016;128:2319–2326.
   PubMed Web of Science ®Google Scholar
• Wan M, Qin J, Songyang Z, et al. OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. J Biol Chem. 2009;284:26725–26731.
   PubMed Web of Science ®Google Scholar
• Rice C, Skordalakes E. Structure and function of the telomeric CST complex. Comput Struct Biotechnol J. 2016;14:161–167.
   PubMed Web of Science ®Google Scholar
• Kasbek C, Wang F, Price CM. Human TEN1 maintains telomere integrity and functions in genome-wide replication restart. J Biol Chem. 2013;288:30139–30150.
   PubMed Web of Science ®Google Scholar
• Said MA, Eppinga RN, Hagemeijer Y, et al. Telomere length and risk of cardiovascular disease and cancer. J Am Coll Cardiol. 2017;70:506–507.
   PubMed Web of Science ®Google Scholar
• Zhan Y, Karlsson IK, Karlsson R, et al. Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study. Circ Res. 2017;121:214–219.
   PubMed Web of Science ®Google Scholar
• Wang H, Chu WS, Lu T, et al. Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion. Am J Physiol Endocrinol Metab. 2004;286:E1–E7.
   PubMed Web of Science ®Google Scholar
• Salpea KD, Talmud PJ, Cooper JA, et al. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis. 2010;209:42–50.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Simmons D, Hambly BD, et al. Interactions between UCP2 SNPs and telomere length exist in the absence of diabetes or pre-diabetes. Sci Rep. 2016;6:33147
   PubMed Web of Science ®Google Scholar
• Reddel RR. The role of senescence and immortalization in carcinogenesis. Carcinogenesis. 2000;21:477–484.
   PubMed Web of Science ®Google Scholar
• Weischer M, Nordestgaard BG, Cawthon RM, et al. Short telomere length, cancer survival, and cancer risk in 47102 individuals. J Natl Cancer Inst. 2013;105:459–468.
   PubMedGoogle Scholar
• Rode L, Nordestgaard BG, Bojesen SE. Long telomeres and cancer risk among 95 568 individuals from the general population. Int J Epidemiol. 2016;45:1634–1643.
   PubMed Web of Science ®Google Scholar
• Willeit P, Willeit J, Kloss-Brandstatter A, et al. Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality. JAMA. 2011;306:42–44.
   PubMed Web of Science ®Google Scholar
• Sanchez-Espiridion B, Chen M, Chang JY, et al. Telomere length in peripheral blood leukocytes and lung cancer risk: a large case-control study in Caucasians. Cancer Res. 2014;74:2476–2486.
   PubMed Web of Science ®Google Scholar
• Campa D, Mergarten B, De Vivo I, et al. Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev. 2014;23:2447–2454.
   PubMed Web of Science ®Google Scholar
• Brummendorf TH, Holyoake TL, Rufer N, et al. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood. 2000;95:1883–1890.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Peniket A, Watkins F, et al. Telomere length shortening in chronic myelogenous leukemia is associated with reduced time to accelerated phase. Blood. 2000;96:358–361.
   PubMed Web of Science ®Google Scholar
• Roos G, Krober A, Grabowski P, et al. Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood. 2008;111:2246–2252.
   PubMed Web of Science ®Google Scholar
• Rossi D, Lobetti Bodoni C, Genuardi E, et al. Telomere length is an independent predictor of survival, treatment requirement and Richter's syndrome transformation in chronic lymphocytic leukemia. Leukemia. 2009;23:1062–1072.
   PubMed Web of Science ®Google Scholar
• Rampazzo E, Bonaldi L, Trentin L, et al. Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes. Haematologica. 2012;97:56–63.
   PubMed Web of Science ®Google Scholar
• Strefford JC, Kadalayil L, Forster J, et al. Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial. Leukemia. 2015;29:2411–2414.
   PubMed Web of Science ®Google Scholar
• Lin TT, Letsolo BT, Jones RE, et al. Telomere dysfunction and fusion during the progression of chronic lymphocytic leukemia: evidence for a telomere crisis. Blood. 2010;116:1899–1907.
   PubMed Web of Science ®Google Scholar
• Grabowski P, Hultdin M, Karlsson K, et al. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood. 2005;105:4807–4812.
   PubMed Web of Science ®Google Scholar
• Zhang C, Doherty JA, Burgess S, et al. Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study. Hum Mol Genet. 2015;24:5356–5366.
   PubMed Web of Science ®Google Scholar
• Ojha J, Codd V, Nelson CP, et al. Genetic variation associated with longer telomere length increases risk of chronic lymphocytic leukemia. Cancer Epidemiol Biomarkers Prev. 2016;25:1043–1049.
   PubMed Web of Science ®Google Scholar
• Machiela MJ, Lan Q, Slager SL, et al. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes. Hum Mol Genet. 2016;25:1663–1676.
   PubMed Web of Science ®Google Scholar
• Jones AM, Beggs AD, Carvajal-Carmona L, et al. TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres. Gut. 2012;61:248–254.
   PubMed Web of Science ®Google Scholar
• Mirabello L, Yu K, Kraft P, et al. The association of telomere length and genetic variation in telomere biology genes. Hum Mutat. 2010;31:1050–1058.
   PubMed Web of Science ®Google Scholar
• Haycock PC, Burgess S, Nounu A, et al. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncol. 2017;3:636–651.
   PubMed Web of Science ®Google Scholar
• Martin-Ruiz CM, Baird D, Roger L, et al. Reproducibility of telomere length assessment: an international collaborative study. Int J Epidemiol. 2015;44:1673–1683.
   PubMed Web of Science ®Google Scholar
• Melin BS, Nordfjall K, Andersson U, et al. hTERT cancer risk genotypes are associated with telomere length. Genet Epidemiol. 2012;36:368–372.
   PubMed Web of Science ®Google Scholar
• Vasa-Nicotera M, Brouilette S, Mangino M, et al. Mapping of a major locus that determines telomere length in humans. Am J Hum Genet. 2005;76:147–151.
   PubMed Web of Science ®Google Scholar
• Mangino M, Brouilette S, Braund P, et al. A regulatory SNP of the BICD1 gene contributes to telomere length variation in humans. Hum Mol Genet. 2008;17:2518–2523.
   PubMed Web of Science ®Google Scholar