title: Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population.
abstract: BACKGROUND
  Short telomeres in peripheral blood leukocytes are associated with older age and age-related diseases. We tested the hypotheses that short telomeres are associated with both increased cancer mortality and all-cause mortality.
  
  
  METHODS
  Individuals (n = 64637) were recruited from 1991 onwards from two Danish prospective cohort studies: the Copenhagen City Heart Study and the Copenhagen General Population Study. All had telomere length measured by quantitative polymerase chain reaction and the genotypes rs1317082 (TERC), rs7726159 (TERT), and rs2487999 (OBFC1) determined. The sum of telomere-shortening alleles from these three genotypes was calculated. We conducted Cox regression analyses and instrumental variable analyses using the allele sum as an instrument. All statistical tests were two-sided.
  
  
  RESULTS
  Among 7607 individuals who died during follow-up (0-22 years, median = 7 years), 2420 had cancer and 2633 had cardiovascular disease as causes of death. Decreasing telomere length deciles were associated with increasing all-cause mortality (P(trend) = 2*10(-15)). The multivariable-adjusted hazard ratio of all-cause mortality was 1.40 (95% confidence interval [CI] = 1.25 to 1.57) for individuals in the shortest vs the longest decile. Results were similar for cancer mortality and cardiovascular mortality. Telomere length decreased 69 base pairs (95% CI = 61 to 76) per allele for the allele sum, and the per-allele hazard ratio for cancer mortality was 0.95 (95% CI = 0.91 to 0.99). Allele sum was not associated with cardiovascular, other, or all-cause mortality.
  
  
  CONCLUSIONS
  Short telomeres in peripheral blood leukocytes were associated with high mortality in association analyses. In contrast, genetically determined short telomeres were associated with low cancer mortality but not with all-cause mortality.
authors: 1) Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark;
authors: Line
authors: L
authors: Rode
authors: 1) Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark; 2) Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark; 3) Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Børge G
authors: BG
authors: Nordestgaard
authors: 1) Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark; 2) Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark; 3) Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. stig.egil.bojesen@regionh.dk.
authors: Stig E
authors: SE
authors: Bojesen
mesh_terms: D000328:Adult; D000368:Aged; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007962:Leukocytes; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016615:Telomere; D059506:Telomere Shortening