title: Systematic correlation of environmental exposure and physiological and self-reported behaviour factors with leukocyte telomere length.
abstract: It is hypothesized that environmental exposures and behaviour influence telomere length, an indicator of cellular ageing. We systematically associated 461 indicators of environmental exposures, physiology and self-reported behaviour with telomere length in data from the US National Health and Nutrition Examination Survey (NHANES) in 1999-2002. Further, we tested whether factors identified in the NHANES participants are also correlated with gene expression of telomere length modifying genes.
  
  
  
  We correlated 461 environmental exposures, behaviours and clinical variables with telomere length, using survey-weighted linear regression, adjusting for sex, age, age squared, race/ethnicity, poverty level, education and born outside the USA, and estimated the false discovery rate to adjust for multiple hypotheses. We conducted a secondary analysis to investigate the correlation between identified environmental variables and gene expression levels of telomere-associated genes in publicly available gene expression samples.
  
  
  
  After correlating 461 variables with telomere length, we found 22 variables significantly associated with telomere length after adjustment for multiple hypotheses. Of these varaibales, 14 were associated with longer telomeres, including biomarkers of polychlorinated biphenyls([PCBs; 0.1 to 0.2 standard deviation (SD) increase for 1 SD increase in PCB level, P  < 0.002] and a form of vitamin A, retinyl stearate. Eight variables associated with shorter telomeres, including biomarkers of cadmium, C-reactive protein and lack of physical activity. We could not conclude that PCBs are correlated with gene expression of telomere-associated genes.
  
  
  
  Both environmental exposures and chronic disease-related risk factors may play a role in telomere length. Our secondary analysis found no evidence of association between PCBs/smoking and gene expression of telomere-associated genes. All correlations between exposures, behaviours and clinical factors and changes in telomere length will require further investigation regarding biological influence of exposure.
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
authors.forename: Chirag J
authors.initials: CJ
authors.lastname: Patel
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
authors.forename: Arjun K
authors.initials: AK
authors.lastname: Manrai
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Corona
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009749:Nutrition Surveys; D012307:Risk Factors; D057566:Self Report; D016615:Telomere / Q000648:ultrastructure*; D059506:Telomere Shortening; D014481:United States
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: aging; environment-wide association study; exposome; gene-environment interaction; genome-wide association study; telomere length