(Hypertension. 2001;37:425.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Genome-Wide Linkage Analysis of Pulse Pressure in Mexican Americans
From the Division of Epidemiology and Institute of Human Genetics (L.D.A.), University of Minnesota, Minneapolis; the Department of Genetics (P.B.S., J.W.M.), Southwest Foundation for Biomedical Research, San Antonio, Tex; the Human Genetics Center (J.E.H.), University of Texas Health Science Center, Houston; and the Department of Medicine (M.P.S.), University of Texas Health Science Center, San Antonio.
Correspondence to Dr Larry Atwood, Division of Epidemiology, University of Minnesota, 1300 South Second St, Suite 300, Minneapolis, MN 55454-1015. E-mail atwood{at}epi.umn.edu
Pulse
pressure, a measure of aortic stiffness, is a strong predictor of
cardiovascular mortality. To locate genes that affect
pulse pressure, we performed genetic analysis on randomly
ascertained families in the San Antonio Family Heart Study. Pulse
pressure was defined as the difference between systolic and
diastolic blood pressures. Likelihood methods were used to
construct a model that had both single-locus and polygenic components
for 46 families (1308 individuals). The single-locus component included
sex-specific and genotype-specific effects of both age and body
mass index. Using this model, we then performed 2-point linkage
analysis in 10 families (440 individuals) that were among the
largest of the 46 families and that had been genotyped for 399
polymorphic markers. The model that contained only the polygenic
component and simple effects of the covariates showed pulse pressure
heritability of 0.21. When the single-locus component was added, the
sex-specific and genotype-specific effects of age and body mass
index were highly significant
(P<0.002). The full model
accounted for 73% of the total variation of pulse pressure. Linkage
analysis using this model with each marker revealed 4 markers
with lod scores >1.9, which is the Lander-Kruglyak suggestive linkage
standard. D21S1440 had a lod
score of 2.78 with a recombination fraction (
) of 0.02.
D7S1799 had a lod score of 2.04
(=0.01), D8S1100 had a lod
score of 1.98 (=0.08), and
D18S844 had a lod score of 1.95
(=0.11). These results are highly correlated with results involving
systolic blood pressure, indicating that pulse pressure may not
be genetically distinct from systolic blood
pressure.
Key Words: population • genetics • blood pressure • hypertension, genetic • cardiovascular diseases
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