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

Frontiers in Genetics

Volumn 4, Issue JAN, 2013, Pages

  Lee, Joseph H ^a,b,c   Cheng, Rong ^a,b   Honig, Lawrence S ^a,b   Feitosa, Mary ^d   Kammerer, Candace M ^e,f   Kang, Min S ^b   Schupf, Nicole ^a,b,c   Lin, Shiow J ^d   Sanders, Jason L ^e,f   Bae, Harold ^g   Druley, Todd ^d   Perls, Thomas ^g   Christensen, Kaare ^h   Province, Michael ^d   Mayeux, Richard ^a,b,c  

^a Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H Sergievsky Center   (United States)

^b Taub Institute College of Physicians and Surgeons Columbia University ^*  (United States)

^c Och Spine at New York Presbyterian Hospitals   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^f UNIVERSITY OF PITTSBURGH   (United States)

^g BOSTON UNIVERSITY MEDICAL CENTER   (United States)

^h UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

Aging; Familial longevity; Family based study; Genome wide association and linkage; Novel genes; Telomere length

Indexed keywords

ADULT; AGED; ALLELE; ARTICLE; CELL AGING; FEMALE; GENE LOCUS; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HERITABILITY; HUMAN; HUMAN CELL; LEUKOCYTE TELOMERE LENGTH; LINKAGE ANALYSIS; LONGEVITY; MAJOR CLINICAL STUDY; MALE; POPULATION GENETIC STRUCTURE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SINGLE NUCLEOTIDE POLYMORPHISM; TELOMERE HOMEOSTASIS;

EID: 84893676384     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2013.00310     Document Type: Article

References (69)

1. Abecasis, G. R., Cherny, S. S., Cookson, W. O., and Cardon, L. R. (2001). GRR: graphical representation of relationship errors. Bioinformatics 17, 742-743. doi: 10.1093/bioinformatics/17.8.742
2. Abecasis, G. R., Cherny, S. S., Cookson, W. O., and Cardon, L. R. (2002). Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97-101. doi: 10.1038/ng786
3. Allison, D. B., Neale, M. C., Zannolli, R., Schork, N. J., Amos, C. I., and Blangero, J. (1999). Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure. Am. J. Hum. Genet. 65, 531-544. doi: 10.1086/302487
4. Almasy, L., and Blangero, J. (1998). Multipoint quantitative-trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62, 1198-1211. doi: 10.1086/301844
5. Almasy, L., and Blangero, J. (2010). Variance component methods for analysis of complex phenotypes. Cold Spring Harb. Protoc. 2010, pdb top77. doi: 10.1101/pdb.top77
6. Andrew, T., Aviv, A., Falchi, M., Surdulescu, G. L., Gardner, J. P., Lu, X., et al. (2006). Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. Am. J. Hum. Genet. 78, 480-486. doi: 10.1086/500052
7. Armanios, M., and Blackburn, E. H. (2012). The telomere syndromes. Nat. Rev. Genet. 13, 693-704. doi: 10.1038/nrg3246
8. Aulchenko, Y. S., Heutink, P., Mackay, I., Bertoli-Avella, A. M., Pullen, J., Vaessen, N., et al. (2004). Linkage disequilibrium in young genetically isolated Dutch population. Eur. J. Hum. Genet. 12, 527-534. doi: 10.1038/sj.ejhg.5201188
9. Aviv, A. (2009). Leukocyte telomere length, hypertension, and atherosclerosis: are there potential mechanistic explanations? Hypertension 53, 590-591. doi: 10.1161/HYPERTENSIONAHA.109.128926
10. Aviv, A. (2012). Genetics of leukocyte telomere length and its role in atherosclerosis. Mutat. Res. 730, 68-74. doi: 10.1016/j.mrfmmm.2011.05.001
11. Aviv, A., Hunt, S. C., Lin, J., Cao, X., Kimura, M., and Blackburn, E. (2011). Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR. Nucleic Acids Res. 39, e134. doi: 10.1093/nar/gkr634
12. Aviv, A., Valdes, A. M., and Spector, T. D. (2006). Human telomere biology: pitfalls of moving from the laboratory to epidemiology. Int. J. Epidemiol. 35, 1424-1429. doi: 10.1093/ije/dyl169
13. Beekman, M., Blauw, G. J., Houwing-Duistermaat, J. J., Brandt, B. W., Westendorp, R. G., and Slagboom, P. E. (2006). Chromosome 4q25, microsomal transfer protein gene, and human longevity: novel data and a meta-analysis of association studies. J. Gerontol. A Biol. Sci. Med. Sci. 61, 355-362. doi: 10.1093/gerona/61.4.355
14. Blangero, J., and Almasy, L. (1997). Multipoint oligogenic linkage analysis of quantitative traits. Genet. Epidemiol. 14, 959-964. doi: 10.1002/(SICI)1098-2272(1997)14:6<959::AID-GEPI66>3.0.CO;2-K
15. Blangero, J., Diego, V. P., Dyer, T. D., Almeida, M., Peralta, J., Kent, J. W., et al. (2013). A kernel of truth: statistical advances in polygenic variance component models for complex human pedigrees. Adv. Genet. 81, 1-31. doi: 10.1016/B978-0-12-407677-8.00001-4
16. Blangero, J., Williams, J. T., and Almasy, L. (2001). Variance component methods for detecting complex trait loci. Adv. Genet. 42, 151-181. doi: 10.1016/S0065-2660(01)42021-9
17. Blank, M., Tang, Y., Yamashita, M., Burkett, S. S., Cheng, S. Y., and Zhang, Y. E. (2012). A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nat. Med. 18, 227-234. doi: 10.1038/nm.2596
18. Boucher, S. E., Cypher, M. A., Carlock, L. R., and Skoff, R. P. (2002). Proteolipid protein gene modulates viability and phenotype of neurons. J. Neurosci. 22, 1772-1783.
19. Broer, L., Codd, V., Nyholt, D. R., Deelen, J., Mangino, M., Willemsen, G., et al. (2013). Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur. J. Hum. Genet. 21, 1163-1168. doi: 10.1038/ejhg.2012.303
20. Cawthon, R. M. (2002). Telomere measurement by quantitative PCR. Nucleic Acids Res. 30, e47. doi: 10.1093/nar/30.10.e47
21. Cawthon, R. M., Smith, K. R., O'brien, E., Sivatchenko, A., and Kerber, R. A. (2003). Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361, 393-395. doi: 10.1016/S0140-6736(03)12384-7
22. Chadwick, D., and Cardew, G. (1997). Telomeres and Telomerase. Chichester; New York: John Wiley & Sons.
23. Chen, H., Meigs, J. B., and Dupuis, J. (2013). Sequence kernel association test for quantitative traits in family samples. Genet Epidemiol. 37, 196-204. doi: 10.1002/gepi.21703
24. Christensen, K., Johnson, T. E., and Vaupel, J. W. (2006). The quest for genetic determinants of human longevity: challenges and insights. Nat. Rev. Genet. 7, 436-448. doi: 10.1038/nrg1871
25. Codd, V., Mangino, M., Van Der Harst, P., Braund, P. S., Kaiser, M., Beveridge, A. J., et al. (2010). Common variants near TERC are associated with mean telomere length. Nat. Genet. 42, 197-199. doi: 10.1038/ng.532
26. Cournil, A., and Kirkwood, T. B. (2001). If you would live long, choose your parents well. Trends Genet. 17, 233-235. doi: 10.1016/S0168-9525(01)02306-X
27. Deelen, J., Beekman, M., Uh, H. W., Helmer, Q., Kuningas, M., Christiansen, L., et al. (2011). Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell 10, 686-698. doi: 10.1111/j.1474-9726.2011.00705.x
28. Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., et al. (2004). Accelerated telomere shortening in response to life stress. Proc. Natl. Acad. Sci. U.S.A. 101, 17312-17315. doi: 10.1073/pnas.0407162101
29. Etzel, C. J., Shete, S., Beasley, T. M., Fernandez, J. R., Allison, D. B., and Amos, C. I. (2003). Effect of Box-Cox transformation on power of Haseman-Elston and maximum-likelihood variance components tests to detect quantitative trait Loci. Hum. Hered. 55, 108-116. doi: 10.1159/000072315
30. Grupe, A., Li, Y., Rowland, C., Nowotny, P., Hinrichs, A. L., Smemo, S., et al. (2006). A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. Am. J. Hum. Genet. 78, 78-88. doi: 10.1086/498851
31. Halaschek-Wiener, J., Amirabbasi-Beik, M., Monfared, N., Pieczyk, M., Sailer, C., Kollar, A., et al. (2009). Genetic variation in healthy oldest-old. PLoS ONE 4:e6641. doi: 10.1371/journal.pone.0006641
32. Hartmann, N., Reichwald, K., Lechel, A., Graf, M., Kirschner, J., Dorn, A., et al. (2009). Telomeres shorten while Tert expression increases during ageing of the short-lived fish Nothobranchius furzeri. Mech. Ageing Dev. 130, 290-296. doi: 10.1016/j.mad.2009.01.003
33. Heath, S. C. (1997). Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. Am. J. Hum. Genet. 61, 748-760. doi: 10.1086/515506
34. Hjelmborg, J. vB., Iachine, I., Skytthe, A., Vaupel, J. W., Mcgue, M., Koskenvuo, M., et al. (2006). Genetic influence on human lifespan and longevity. Hum. Genet. 119, 312-321. doi: 10.1007/s00439-006-0144-y
35. Holt, S. E., Shay, J. W., and Wright, W. E. (1996). Refining the telomere-telomerase hypothesis of aging and cancer. Nat. Biotechnol. 14, 836-839. doi: 10.1038/nbt0796-836
36. Honig, L. S., Kang, M. S., Schupf, N., Lee, J. H., and Mayeux, R. (2012). Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch. Neurol. 69, 1332-1339. doi: 10.1001/archneurol.2012.1541
37. Jeanclos, E., Krolewski, A., Skurnick, J., Kimura, M., Aviv, H., Warram, J. H., et al. (1998). Shortened telomere length in white blood cells of patients with IDDM. Diabetes 47, 482-486. doi: 10.2337/diabetes.47.3.482
38. Kaplan, R. C., Fitzpatrick, A. L., Pollak, M. N., Gardner, J. P., Jenny, N. S., Mcginn, A. P., et al. (2009). Insulin-like growth factors and leukocyte telomere length: the cardiovascular health study. J. Gerontol. A Biol. Sci. Med. Sci. 64, 1103-1106. doi: 10.1093/gerona/glp036
39. Lee, J. H., Flaquer, A., Costa, R., Andrews, H., Cross, P., Lantigua, R., et al. (2004). Genetic influences on life span and survival among elderly African-Americans, Caribbean Hispanics, and Caucasians. Am. J. Med. Genet. A 128A, 159-164. doi: 10.1002/ajmg.a.30062
40. Levy, D., Neuhausen, S. L., Hunt, S. C., Kimura, M., Hwang, S. J., Chen, W., et al. (2010). Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc. Natl. Acad. Sci. U.S.A. 107, 9293-9298. doi: 10.1073/pnas.0911494107
41. Magrane, M., and Consortium, U. (2011). UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford) 2011, bar009. doi: 10.1093/database/bar009
42. Mangino, M., Hwang, S. J., Spector, T. D., Hunt, S. C., Kimura, M., Fitzpatrick, A. L., et al. (2012). Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum. Mol. Genet. 21, 5385-5394. doi: 10.1093/hmg/dds382
43. Mangino, M., Richards, J. B., Soranzo, N., Zhai, G., Aviv, A., Valdes, A. M., et al. (2009). A genome-wide association study identifies a novel locus on chromosome 18q12.2 influencing white cell telomere length. J. Med. Genet. 46, 451-454. doi: 10.1136/jmg.2008.064956
44. Mosing, M. A., Verweij, K. J., Medland, S. E., Painter, J., Gordon, S. D., Heath, A. C., et al. (2010). A genome-wide association study of self-rated health. Twin Res. Hum. Genet. 13, 398-403. doi: 10.1375/twin.13.4.398
45. Murabito, J. M., Yuan, R., and Lunetta, K. L. (2012). The search for longevity and healthy aging genes: insights from epidemiological studies and samples of long-lived individuals. J. Gerontol. A Biol. Sci. Med. Sci. 67, 470-479. doi: 10.1093/gerona/gls089
46. Newman, A. B., Glynn, N. W., Taylor, C. A., Sebastiani, P., Perls, T. T., Mayeux, R., et al. (2011). Health and function of participants in the Long Life Family Study: a comparison with other cohorts. Aging (Albany. NY). 3, 63-76.
47. O'Connell, J. R. (2000). Zero-recombinant haplotyping: applications to fine mapping using SNPs. Genet. Epidemiol. 19(Suppl. 1), S64-S70. doi: 10.1002/1098-2272(2000)19:1+<::AID-GEPI10>3.0.CO;2-G
48. Ott, J. (1983). Linkage analysis and family classification under heterogeneity. Ann. Hum. Genet. 47, 311-320. doi: 10.1111/j.1469-1809.1983.tb01001.x
49. Patterson, N., Price, A. L., and Reich, D. (2006). Population structure and eigenanalysis. PLoS Genet. 2:e190. doi: 10.1371/journal.pgen.0020190
50. Pedersen, C. B., Gotzsche, H., Moller, J. O., and Mortensen, P. B. (2006). The danish civil registration system. A cohort of eight million persons. Dan. Med. Bull. 53, 441-449.
51. Perls, T., Kohler, I. V., Andersen, S., Schoenhofen, E., Pennington, J., Young, R., et al. (2007). Survival of parents and siblings of supercentenarians. J. Gerontol. A Biol. Sci. Med. Sci. 62, 1028-1034. doi: 10.1093/gerona/62.9.1028
52. Perls, T. T., Bubrick, E., Wager, C. G., Vijg, J., and Kruglyak, L. (1998). Siblings of centenarians live longer. Lancet 351, 1560. doi: 10.1016/S0140-6736(05)61126-9
53. Perls, T., and Terry, D. (2003). Genetics of exceptional longevity. Exp. Gerontol. 38, 725-730. doi: 10.1016/S0531-5565(03)00098-6
54. Perls, T., Terry, D. F., Silver, M., Shea, M., Bowen, J., Joyce, E., et al. (2000). Centenarians and the genetics of longevity. Results Probl. Cell Differ. 29, 1-20. doi: 10.1007/978-3-540-48003-7_1
55. Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., and Reich, D. (2006). Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904-909. doi: 10.1038/ng1847
56. Puca, A. A., Daly, M. J., Brewster, S. J., Matise, T. C., Barrett, J., Shea-Drinkwater, M., et al. (2001). A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proc. Natl. Acad. Sci. U.S.A. 98, 10505-10508. doi: 10.1073/pnas.181337598
57. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., et al. (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575. doi: 10.1086/519795
58. Sanders, J. L., Fitzpatrick, A. L., Boudreau, R. M., Arnold, A. M., Aviv, A., Kimura, M., et al. (2012). Leukocyte telomere length is associated with noninvasively measured age-related disease: the cardiovascular health study. J. Gerontol. A Biol. Sci. Med. Sci. 67, 409-416. doi: 10.1093/gerona/glr173
59. Sanders, J. L., and Newman, A. B. (2013). Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol Rev. 35, 112-131. doi: 10.1093/epirev/mxs008
60. Sebastiani, P., Hadley, E. C., Province, M., Christensen, K., Rossi, W., Perls, T. T., et al. (2009). A family longevity selection score: ranking sibships by their longevity, size, and availability for study. Am. J. Epidemiol. 170, 1555-1562. doi: 10.1093/aje/kwp309
61. Shaffer, J. A., Epel, E., Kang, M. S., Ye, S., Schwartz, J. E., Davidson, K. W., et al. (2012). Depressive symptoms are not associated with leukocyte telomere length: findings from the Nova Scotia Health Survey (NSHS95), a population-based study. PLoS ONE 7:e48318. doi: 10.1371/journal.pone.0048318
62. Shay, J. W., and Wright, W. E. (2001). Ageing and cancer: the telomere and telomerase connection. Novartis Found. Symp. 235, 116-125. discussion: 125-119, 146-119. doi: 10.1002/0470868694.ch11
63. Smith, C. A. B. (1961). "Homogeneity test for linkage data," in Proceedings From the Second International Congress of Human Genetics (Rome), 6-12.
64. Soerensen, M., Thinggaard, M., Nygaard, M., Dato, S., Tan, Q., Hjelmborg, J., et al. (2012). Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis. Aging Cell 11, 223-227. doi: 10.1111/j.1474-9726.2011.00775.x
65. SPSS, (2013). "IBM SPSS Statistics for Windows." 21.0 Edn. (Armonk, NY: IBM Corp).
66. Therneau, T., Atkinson, E., Sinnwell, J., Matsumoto, M., Schaid, D., and Mcdonnell, S. (2012). Package 'kinship2' [Online]. Available online at: http://cran.r-project.org/web/packages/kinship2/kinship2.pdf
67. Vasa-Nicotera, M., Brouilette, S., Mangino, M., Thompson, J. R., Braund, P., Clemitson, J. R., et al. (2005). Mapping of a major locus that determines telomere length in humans. Am. J. Hum. Genet. 76, 147-151. doi: 10.1086/426734
68. Wu, M. C., Lee, S., Cai, T., Li, Y., Boehnke, M., and Lin, X. (2011). Rare-variant association testing for sequencing data with the sequence kernel association test. Am. J. Hum. Genet. 89, 82-93. doi: 10.1016/j.ajhg.2011.05.029
69. Ye, S., Shaffer, J. A., Kang, M. S., Harlapur, M., Muntner, P., Epel, E., et al. (2013). Relation between leukocyte telomere length and incident coronary heart disease events (from the 1995 canadian nova scotia health survey). Am. J. Cardiol. 111, 962-967. doi: 10.1016/j.amjcard.2012.12.017