title: Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature.
abstract: BACKGROUND
  Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias.
  
  
  METHODS
  We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature.
  
  
  RESULTS
  In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18 mm Hg lower systolic BP [SBP; β ± SE = -0.18 ± 0.05 mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; -0.10 ± 0.03 mm Hg; P = 0.001]. Similar results were seen in the BPRHS for SBP only. Clock genes explained a statistically significant proportion of the variance in SBP [V G/V P ± SE = 0.071 ± 0.03; P = 0.001] in GOLDN, but not in the BPRHS, and we did not observe associations between individual SNPs and BP. Environmental temperature did not influence the identified genetic associations.
  
  
  CONCLUSIONS
  We identified clock genes that explained a statistically significant proportion of the phenotypic variance in SBP, supporting the importance of the circadian pathway underlying cardiac physiology. Although temperature was associated with BP, it did not affect results with genetic markers in either study. Therefore, it does not appear that temperature measures are necessary for interpreting associations between clock genes and BP.
  
  
  BACKGROUND
  Trials related to this study were registered at clinicaltrials.gov as NCT00083369 (Genetic and Environmental Determinants of Triglycerides) and NCT01231958 (Boston Puerto Rican Health Study).
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; hassan.dashti@tufts.edu.
authors.forename: Hassan S
authors.initials: HS
authors.lastname: Dashti
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA;
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA;
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA;
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA;
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamon-Fava
authors.affiliation: Nutritional Epidemiology Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA;
authors.forename: Paul
authors.initials: P
authors.lastname: Jacques
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA;
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: University of Massachusetts Lowell, Lowell, Massachusetts, USA;
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA;
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000235:genetics*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013599:Systole; D013696:Temperature
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D004247:DNA
keywords: blood pressure; circadian clocks; circadian rhythm; clock genes; environmental temperature; hypertension.