Publication Date:
2012-12-01
Description:
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 x 10 –11 ) and with the telomerase RNA component TERC (rs1317082, P = 1.1 x 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 x 10 –8 ) on chromosome17p13.1 and zinc finger protein 676 ( ZNF676; rs412658, P = 3.3 x 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.
Print ISSN:
0964-6906
Electronic ISSN:
1460-2083
Topics:
Biology
,
Medicine
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