Journal
HUMAN MOLECULAR GENETICS
Volume 21, Issue 24, Pages 5385-5394Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/dds382
Keywords
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Funding
- Wellcome Trust
- European Community [HEALTH-F4-2007-201413]
- Dept of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- ERC
- National Eye Institute via an NIH/CIDR
- National Institute of Child Health and Human Development [HD-061437, HD-062783]
- National Institute on Aging [AG-16592]
- NIH [N01-HC-25195]
- National Heart, Lung, and Blood Institute
- Center for Population Studies of the NHLBI
- NHLBI [1 R01 HL80698-01, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756]
- NIA [AG-23629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
- National Center of Advancing Translational Technologies CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- Cedars-Sinai Board of Governors' Chair in Medical Genetics
- NIH: Human Telomere Genetics [R01AG20132]
- Telomeres Vascular Aging [R01AG21593]
- Leukocyte Telomere Dynamics, Gender, Menopause, Insulin Resistance [R01AG030678]
- US-Israel Binational Science Foundation
- Israel Science Foundation
- French Fondation pour la Recherche Medicale [FRM DCV2007-0409250]
- Plan Pluriformation [PPF815 PSVT-2005]
- National Institutes of Health [HHSN268200782096C]
- NIH, National Institute on Aging
- [HL54471]
- [HL54472]
- [HL54473]
- [HL54495]
- [HL54496]
- [HL54509]
- [HL54515]
- [HL055673]
- Direct For Social, Behav & Economic Scie
- Division Of Behavioral and Cognitive Sci [0827436] Funding Source: National Science Foundation
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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.
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