title: Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.
abstract: BACKGROUND
  Although cross-sectional studies have linked higher body mass index (BMI) and type 2 diabetes (T2D) to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL).
  
  
  METHODS
  We conducted an analysis of 3,968 women of European ancestry aged 43-70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D.
  
  
  RESULTS
  After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: -0.01; SE: 0.02; P = 0.52). Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: -0.006; SE: 0.02; P = 0.69).
  
  
  CONCLUSIONS
  In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.
authors: Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, United States of America. mdu@fhcrc.org
authors: Mengmeng
authors: M
authors: Du
authors: Jennifer
authors: J
authors: Prescott
authors: Marilyn C
authors: MC
authors: Cornelis
authors: Susan E
authors: SE
authors: Hankinson
authors: Edward
authors: E
authors: Giovannucci
authors: Peter
authors: P
authors: Kraft
authors: Immaculata
authors: I
authors: De Vivo
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008875:Middle Aged; D009726:Nurses / Q000706:statistics & numerical data*; D016615:Telomere / Q000235:genetics*; D059506:Telomere Shortening / Q000235:genetics