Published Online
on June 16, 2009

A more recent version of this article appeared on August 1, 2009

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Original Article

Social– and Behavioral–Specific Genetic Effects on Blood Pressure Traits: The Strong Heart Family Study

Nora Franceschini^1,8; Kathryn M. Rose¹; Kristi L. Storti²; Sue Rutherford³; V. Saroja Voruganti³; Sandy Laston³; Harald H.H. Göring³; Thomas D. Dyer³; Jason G. Umans⁴; Elisa T. Lee⁵; Lyle G. Best⁶; Richard R. Fabsitz⁷; Shelley A. Cole³; Jean W. MacCluer³ and Kari E. North¹

¹ University of North Carolina, Chapel Hill, NC;
² University of Pittsburgh, Pittsburgh, PA;
³ Southwest Foundation for Biomedical Research, San Antonio, TX;
⁴ Georgetown University Medical Center & MedStar Research Institute, Washington, DC;
⁵ University of Oklahoma Health Sciences Center, Oklahoma City, OK;
⁶ Missouri Breaks Industries Research, Inc., Timber Lake, SD;
⁷ National Heart, Lung, and Blood Institute, Bethesda, MD

⁸ E-mail: noraf{at}unc.edu

Background—Population studies have demonstrated an important role of social, behavioral, and environmental factors in blood pressure levels. Accounting for the genetic interaction of these factors may help to identify common blood pressure susceptibility alleles.

Methods and Results—We studied the interaction of additive genetic effects and behavioral (physical activity, smoking, alcohol use) and socioeconomic (education) factors on blood pressure in approximately 3,600 American Indians participants of the Strong Heart Family Study, using variance component models. The mean and standard deviation of resting systolic and diastolic blood pressures were 123 ± 17 and 76 ± 11 mm Hg, respectively. We detected evidence for distinct genetic effects on diastolic blood pressure among ever smokers compared to never smokers (P=0.01). For alcohol intake, we observed significant genotype-by-environment interactions on diastolic (g=0.10, P = 0.0003) and on systolic blood pressures (g= 0.59, P= 0.0008) among current drinkers compared to former or never drinkers. We also detected genotype-by-physical activity interactions on diastolic blood pressure (g=0.35, P = 0.0004). Lastly, there was evidence for distinct genetic effects on diastolic blood pressure among individuals with less than high school education compared to those with 12 or more years of education (g= 0.41, P = 0.02).

Conclusions—Our findings suggest that behavioral and socioeconomic factors can modify the genetic effects on blood pressure phenotypes. Accounting for context dependent factors may help us to better understand the complexities of the gene effects on blood pressure and other complex phenotypes with high levels of genetic heterogeneity.

Key Words: blood pressure • epidemiology • genetics • hypertension