Published online before print June 16, 2009, doi: 10.1161/CIRCGENETICS.109.853630
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Original Articles |
Social- and Behavioral-Specific Genetic Effects on Blood Pressure Traits
The Strong Heart Family Study
From the Department of Epidemiology (N.F., K.M.R., K.E.N.), University of North Carolina, Chapel Hill, NC; Department of Epidemiology (K.L.S.), University of Pittsburgh, Pittsburgh, Pa; Department of Genetics (S.R., S.V., S.L., H.H.H.G., T.D.D., S.A.C., J.W.M.C.), Southwest Foundation for Biomedical Research, San Antonio, Tex; Division of Nephrology and Hypertension (J.G.U.), Georgetown University Medical Center, Washington, DC; MedStar Research Institute (J.G.U.), Washington, DC; Center for American Indian Health Research (E.T.L.), College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Okla; Missouri Breaks Industries Research, Inc (L.G.B.), Timber Lake, SD; Epidemiology and Biometry Program (R.R.F.), National Heart, Lung, and Blood Institute, Bethesda, Md; and Center for Genome Sciences (K.E.N.), University of North Carolina, Chapel Hill, NC.
Correspondence to Nora Franceschini, MD, MPH, Department of Epidemiology, University of North Carolina Chapel Hill, 137 E Franklin St, Suite 306 CB#8050, Chapel Hill, NC 27514. E-mail noraf{at}unc.edu
Received January 23, 2009; accepted April 30, 2009.
Background— Population studies have demonstrated an important role of social, behavioral, and environmental factors in blood pressure (BP) levels. Accounting for the genetic interaction of these factors may help to identify common BP 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 BP in 
3600 American Indian participants of the Strong Heart Family Study, using variance component models. The mean and SD of resting systolic and diastolic BPs were 123±17 and 76±11 mm Hg, respectively. We detected evidence for distinct genetic effects on diastolic BP among ever smokers compared with 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 BPs (g=0.59, P=0.0008) among current drinkers compared with former or never drinkers. We also detected genotype-by-physical activity interactions on diastolic BP (g=0.35, P=0.0004). Finally, there was evidence for distinct genetic effects on diastolic BP among individuals with less than high school education compared with 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 BP phenotypes. Accounting for context dependent factors may help us to better understand the complexities of the gene effects on BP and other complex phenotypes with high levels of genetic heterogeneity.
Key Words: blood pressure • hypertension • epidemiology • genetics
CLINICAL PERSPECTIVE
The online-only Data Supplement is available at http://circgenetics.ahajournals.org/cgi/content/full/CIRCGENETICS.108.853630/DC1.The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the Indian Health Service.