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Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.
Tuesday,2013-10-01 10:23 America/Los_Angeles — poolea2
| Title | Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | 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, Shamieh, SEl, 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 |
| Journal | Hum Mol Genet |
| Volume | 21 |
| Issue | 24 |
| Pagination | 5385-94 |
| Date Published | 2012 Dec 15 |
| ISSN | 1460-2083 |
| Keywords | Genome-Wide Association Study, Humans, Kruppel-Like Transcription Factors, Telomere, Telomere Homeostasis, Telomere-Binding Proteins |
| Abstract | <p>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.</p> |
| DOI | 10.1093/hmg/dds382 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 23001564 |
| PubMed Central ID | PMC3510758 |
| Grant List | N01-HC-25195 / HC / NHLBI NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States HL055673 / HL / NHLBI NIH HHS / United States HL54515 / HL / NHLBI NIH HHS / United States R01 AG016592 / AG / NIA NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States R01AG21593 / AG / NIA NIH HHS / United States / / Intramural NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States HL54496 / HL / NHLBI NIH HHS / United States 1 R01 HL80698-01 / HL / NHLBI NIH HHS / United States R01AG20132 / AG / NIA NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States HL54473 / HL / NHLBI NIH HHS / United States HD-062783 / HD / NICHD NIH HHS / United States AG-16592 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HHSN268200782096C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01AG62106 / AG / NIA NIH HHS / United States HL54495 / HL / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States HD-061437 / HD / NICHD NIH HHS / United States R01AG030678 / AG / NIA NIH HHS / United States / / Wellcome Trust / United Kingdom AG 023629 / AG / NIA NIH HHS / United States HL54471 / HL / NHLBI NIH HHS / United States HL54509 / HL / NHLBI NIH HHS / United States K24 CA169004 / CA / NCI NIH HHS / United States HL54472 / HL / NHLBI NIH HHS / United States |