Abstract
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.