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Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.

Publication ,  Journal Article
Mangino, M; Hwang, S-J; Spector, TD; Hunt, SC; Kimura, M; Fitzpatrick, AL; Christiansen, L; Petersen, I; Elbers, CC; Harris, T; Chen, W ...
Published in: Hum Mol Genet
December 15, 2012

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 15, 2012

Volume

21

Issue

24

Start / End Page

5385 / 5394

Location

England

Related Subject Headings

  • Telomere-Binding Proteins
  • Telomere Homeostasis
  • Telomere
  • Kruppel-Like Transcription Factors
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
 

Citation

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Mangino, M., Hwang, S.-J., Spector, T. D., Hunt, S. C., Kimura, M., Fitzpatrick, A. L., … Aviv, A. (2012). Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet, 21(24), 5385–5394. https://doi.org/10.1093/hmg/dds382
Mangino, Massimo, Shih-Jen Hwang, Timothy D. Spector, Steven C. Hunt, Masayuki Kimura, Annette L. Fitzpatrick, Lene Christiansen, et al. “Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.Hum Mol Genet 21, no. 24 (December 15, 2012): 5385–94. https://doi.org/10.1093/hmg/dds382.
Mangino M, Hwang S-J, Spector TD, Hunt SC, Kimura M, Fitzpatrick AL, et al. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet. 2012 Dec 15;21(24):5385–94.
Mangino, Massimo, et al. “Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.Hum Mol Genet, vol. 21, no. 24, Dec. 2012, pp. 5385–94. Pubmed, doi:10.1093/hmg/dds382.
Mangino M, Hwang S-J, Spector TD, Hunt SC, Kimura M, Fitzpatrick AL, Christiansen L, Petersen I, Elbers CC, Harris T, Chen W, Srinivasan SR, Kark JD, Benetos A, El Shamieh S, Visvikis-Siest S, Christensen K, Berenson GS, Valdes AM, Viñuela A, Garcia M, Arnett DK, Broeckel U, Province MA, Pankow JS, Kammerer C, Liu Y, Nalls M, Tishkoff S, Thomas F, Ziv E, Psaty BM, Bis JC, Rotter JI, Taylor KD, Smith E, Schork NJ, Levy D, Aviv A. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet. 2012 Dec 15;21(24):5385–5394.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 15, 2012

Volume

21

Issue

24

Start / End Page

5385 / 5394

Location

England

Related Subject Headings

  • Telomere-Binding Proteins
  • Telomere Homeostasis
  • Telomere
  • Kruppel-Like Transcription Factors
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • 11 Medical and Health Sciences
  • 06 Biological Sciences