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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.

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