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American Journal of Epidemiology Advance Access published online on August 23, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj295
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received December 16, 2005
Accepted April 12, 2006

ORIGINAL CONTRIBUTIONS

Heritability of the Ankle-Brachial Index

Joanne M. Murabito 1 *, Chao-Yu Guo 2, Caroline S. Fox 3, and Ralph B. D'Agostino 2

1 Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA; Section of General Internal Medicine, Boston University School of Medicine, Boston, MA
2 Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA; Statistics and Consulting Unit, Boston University, Boston, MA
3 Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA; National Heart, Lung, and Blood Institute, Bethesda, MD; Department of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

* To whom correspondence should be addressed.
Joanne M. Murabito, E-mail: murabito{at}bu.edu


  Abstract

The ankle-brachial blood pressure index (ABI) is a widely utilized measure for detecting peripheral arterial disease. Genetic contributions to variation in ABI are largely unknown. The authors sought to estimate ABI heritability in a community-based sample. From 1995 to 1998, ABI was measured in 1,097 men and 1,189 women (mean age = 57 years; range, 29-85 years) from 999 families in the Framingham Offspring cohort. Correlation coefficients for sibling pairs were calculated using the family correlations (FCOR) procedure in S.A.G.E. (Case Western Reserve University, Cleveland, Ohio). The heritability of ABI was estimated using variance-components methods in SOLAR (Southwest Foundation for Biomedical Research, San Antonio, Texas). Analyses were performed on normalized crude ABI and on normalized residuals from multiple linear regression analyses in SAS (SAS Institute, Inc., Cary, North Carolina) that adjusted for age, sex, smoking, diabetes, hypertension, ratio of total cholesterol to high density lipoprotein cholesterol, log triglyceride level, and body mass index. The mean ABI was 1.1 (range, 0.4-1.4). The age- and sex-adjusted and multivariable-adjusted sibling-pair correlation coefficients for normalized ABI were 0.15 and 0.11, respectively, resulting in heritability estimates of 0.30 and 0.22. Crude, age- and sex-adjusted, and multivariable-adjusted heritabilities for normalized ABI estimated using variance-components analysis were 0.27 (standard error, 0.06), 0.30 (standard error, 0.06), and 0.21 (standard error, 0.06), respectively (all p values < 0.0001). A modest proportion of the variability in ABI is explained by genetic factors.

Keywords: blood pressure; genetic predisposition to disease; peripheral vascular diseases.
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