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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;4:310doi: 10.3389/fgene.2013.00310.
Lee, J. H., Cheng, R., Honig, L. S., Feitosa, M., Kammerer, C. M., Kang, M. S., Schupf, N., Lin, S. J., Sanders, J. L., Bae, H., Druley, T., Perls, T., Christensen, K., Province, M., & Mayeux, R. (2013). 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, 4310. https://doi.org/10.3389/fgene.2013.00310
Lee, Joseph H, 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." Frontiers in genetics vol. 4 (2013): 310. doi: https://doi.org/10.3389/fgene.2013.00310
Lee JH, Cheng R, Honig LS, Feitosa M, Kammerer CM, Kang MS, Schupf N, Lin SJ, Sanders JL, Bae H, Druley T, Perls T, Christensen K, Province M, Mayeux R. 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 Jan 17;4:310. doi: 10.3389/fgene.2013.00310. eCollection 2013. PMID: 24478790; PMCID: PMC3894567.
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Front Genet. 2014 Jan 17;4:310. doi: 10.3389/fgene.2013.00310. eCollection 2013.

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

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

Affiliations

  1. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Taub Institute, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Department of Epidemiology, School of Public Health, Columbia University New York, NY, USA.
  2. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Taub Institute, College of Physicians and Surgeons, Columbia University New York, NY, USA.
  3. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Taub Institute, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Department of Neurology, College of Physicians and Surgeons, Columbia University New York, NY, USA.
  4. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine St. Louis, MO, USA.
  5. Department of Epidemiology, University of Pittsburgh Pittsburgh, PA, USA ; Department of Human Genetics, University of Pittsburgh Pittsburgh, PA, USA ; Center for Aging and Population Health, University of Pittsburgh Pittsburgh, PA, USA.
  6. Taub Institute, College of Physicians and Surgeons, Columbia University New York, NY, USA.
  7. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Taub Institute, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Department of Epidemiology, School of Public Health, Columbia University New York, NY, USA ; Department of Psychiatry, College of Physicians and Surgeons, Columbia University New York, NY, USA.
  8. Department of Epidemiology, University of Pittsburgh Pittsburgh, PA, USA ; Center for Aging and Population Health, University of Pittsburgh Pittsburgh, PA, USA.
  9. Department of Biostatistics, Boston University Medical Center Boston, MA, USA.
  10. Department of Pediatrics and Genetics, Washington University School of Medicine St. Louis, MO, USA.
  11. Department of Medicine, Boston University Medical Center Boston, MA, USA.
  12. The Danish Aging Research Center, Epidemiology, University of Southern Denmark Odense, Denmark.
  13. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Taub Institute, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Department of Epidemiology, School of Public Health, Columbia University New York, NY, USA ; Department of Neurology, College of Physicians and Surgeons, Columbia University New York, NY, USA ; Department of Psychiatry, College of Physicians and Surgeons, Columbia University New York, NY, USA.

PMID: 24478790 PMCID: PMC3894567 DOI: 10.3389/fgene.2013.00310

Abstract

Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near PAPSS1 and DKK2 on 4q25 (p = 4.7E-8). From our linkage analysis, we identified two additional novel loci with HLOD scores exceeding three, including 4.77 for 17q23.2, and 4.36 for 10q11.21. These two loci harbor a number of novel candidate genes with SNPs, and our gene-wise association analysis identified multiple genes, including DCAF7, POLG2, CEP95, and SMURF2 at 17q23.2; and RASGEF1A, HNRNPF, ANF487, CSTF2T, and PRKG1 at 10q11.21. Among these genes, multiple SNPs were associated with leukocyte telomere length, but the strongest association was observed with one contiguous haplotype in CEP95 and SMURF2. We also show that three previously reported genes-TERC, MYNN, and OBFC1-were significantly associated with leukocyte telomere length at p empirical < 0.05.

Keywords: aging; familial longevity; family-based study; genome wide association and linkage; novel genes; telomere length

References

  1. J Neurosci. 2002 Mar 1;22(5):1772-83 - PubMed
  2. Hum Mol Genet. 2012 Dec 15;21(24):5385-94 - PubMed
  3. Am J Hum Genet. 1999 Aug;65(2):531-44 - PubMed
  4. Nat Genet. 2006 Aug;38(8):904-9 - PubMed
  5. Dan Med Bull. 2006 Nov;53(4):441-9 - PubMed
  6. Twin Res Hum Genet. 2010 Aug;13(4):398-403 - PubMed
  7. J Gerontol A Biol Sci Med Sci. 2009 Nov;64(11):1103-6 - PubMed
  8. Am J Med Genet A. 2004 Jul 15;128A(2):159-64 - PubMed
  9. Nat Biotechnol. 1996 Jul;14(7):836-9 - PubMed
  10. Cold Spring Harb Protoc. 2010 May;2010(5):pdb.top77 - PubMed
  11. Nat Genet. 2010 Mar;42(3):197-9 - PubMed
  12. Genet Epidemiol. 2000;19 Suppl 1:S64-70 - PubMed
  13. Am J Hum Genet. 1998 May;62(5):1198-211 - PubMed
  14. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9293-8 - PubMed
  15. Nat Rev Genet. 2012 Oct;13(10):693-704 - PubMed
  16. Trends Genet. 2001 May;17(5):233-5 - PubMed
  17. Int J Epidemiol. 2006 Dec;35(6):1424-9 - PubMed
  18. Hum Genet. 2006 Apr;119(3):312-21 - PubMed
  19. Am J Cardiol. 2013 Apr 1;111(7):962-7 - PubMed
  20. Nucleic Acids Res. 2002 May 15;30(10):e47 - PubMed
  21. Genet Epidemiol. 1997;14(6):959-64 - PubMed
  22. Eur J Hum Genet. 2004 Jul;12(7):527-34 - PubMed
  23. Adv Genet. 2001;42:151-81 - PubMed
  24. Exp Gerontol. 2003 Jul;38(7):725-30 - PubMed
  25. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10505-8 - PubMed
  26. Lancet. 1998 May 23;351(9115):1560 - PubMed
  27. Bioinformatics. 2001 Aug;17(8):742-3 - PubMed
  28. Am J Hum Genet. 1997 Sep;61(3):748-60 - PubMed
  29. J Med Genet. 2009 Jul;46(7):451-4 - PubMed
  30. Am J Hum Genet. 2006 Mar;78(3):480-6 - PubMed
  31. PLoS One. 2009 Aug 14;4(8):e6641 - PubMed
  32. J Gerontol A Biol Sci Med Sci. 2006 Apr;61(4):355-62 - PubMed
  33. Nat Med. 2012 Jan 08;18(2):227-34 - PubMed
  34. J Gerontol A Biol Sci Med Sci. 2012 May;67(5):470-9 - PubMed
  35. Nat Genet. 2002 Jan;30(1):97-101 - PubMed
  36. Eur J Hum Genet. 2013 Oct;21(10):1163-8 - PubMed
  37. Genet Epidemiol. 2013 Feb;37(2):196-204 - PubMed
  38. Am J Epidemiol. 2009 Dec 15;170(12):1555-62 - PubMed
  39. Mutat Res. 2012 Feb 1;730(1-2):68-74 - PubMed
  40. Epidemiol Rev. 2013;35:112-31 - PubMed
  41. Nucleic Acids Res. 2011 Nov 1;39(20):e134 - PubMed
  42. Nat Rev Genet. 2006 Jun;7(6):436-48 - PubMed
  43. Lancet. 2003 Feb 1;361(9355):393-5 - PubMed
  44. Am J Hum Genet. 2005 Jan;76(1):147-51 - PubMed
  45. Hypertension. 2009 Apr;53(4):590-1 - PubMed
  46. Am J Hum Genet. 2006 Jan;78(1):78-88 - PubMed
  47. Novartis Found Symp. 2001;235:116-25; discussion 125-9, 146-9 - PubMed
  48. PLoS Genet. 2006 Dec;2(12):e190 - PubMed
  49. Database (Oxford). 2011 Mar 29;2011:bar009 - PubMed
  50. Aging (Albany NY). 2011 Jan;3(1):63-76 - PubMed
  51. Arch Neurol. 2012 Oct;69(10):1332-9 - PubMed
  52. Mech Ageing Dev. 2009 May;130(5):290-6 - PubMed
  53. Adv Genet. 2013;81:1-31 - PubMed
  54. J Gerontol A Biol Sci Med Sci. 2007 Sep;62(9):1028-34 - PubMed
  55. Am J Hum Genet. 2007 Sep;81(3):559-75 - PubMed
  56. Am J Hum Genet. 2011 Jul 15;89(1):82-93 - PubMed
  57. Hum Hered. 2003;55(2-3):108-16 - PubMed
  58. Results Probl Cell Differ. 2000;29:1-20 - PubMed
  59. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5 - PubMed
  60. J Gerontol A Biol Sci Med Sci. 2012 Apr;67(4):409-16 - PubMed
  61. Aging Cell. 2012 Apr;11(2):223-7 - PubMed
  62. PLoS One. 2012;7(10):e48318 - PubMed
  63. Diabetes. 1998 Mar;47(3):482-6 - PubMed
  64. Ann Hum Genet. 1983 Oct;47(4):311-20 - PubMed
  65. Aging Cell. 2011 Aug;10(4):686-98 - PubMed

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