title: Heritability, linkage, and genetic associations of exercise treadmill test responses.
abstract: BACKGROUND
  The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown.
  
  
  RESULTS
  We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43-44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing.
  
  
  CONCLUSIONS
  Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.
authors.affiliation: Framingham Study, Framingham, Mass, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Jared A
authors.initials: JA
authors.lastname: Drake
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Musone
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Heard-Costa
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Larry D
authors.initials: LD
authors.lastname: Atwood
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D003971:Diastole; D005080:Exercise Test; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000502:physiology*; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011237:Predictive Value of Tests; D019655:Quantitative Trait, Heritable; D013599:Systole