Published Online
on April 24, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on October 29, 2002
Accepted on October 30, 2002

Evaluating the Context-Dependent Effect of Family History of Stroke in a Genome Scan for Hypertension

Alanna C. Morrison PhD^*; Andrew Brown MD, MPH; Sharon L.R. Kardia PhD; Stephen T. Turner MD; Eric Boerwinkle PhD; and for the Genetic Epidemiology Network of Arteriopathy (GENOA) Study

From the Human Genetics Center, University of Texas, Houston Health Science Center, Houston (A.C.M., E.B.); Department of Medicine, University of Mississippi Medical Center, Jackson, Miss (A.B.); Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor (S.L.R.K.); Division of Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minn (S.T.T.); and Institute of Molecular Medicine, Houston, Tex (E.B.).

^* To whom correspondence should be addressed. E-mail: Alanna.C.Morrison{at}uth.tmc.edu.

Background and Purpose--Hypertension is an important risk factor for stroke, and the 2 diseases may share susceptibility genes in common. We sought to identify genomic regions influencing susceptibility to both hypertension and stroke.

Subjects and Methods--Genome-wide linkage scans were performed in samples of 338 white and 265 black hypertensive sibships recruited by the Genetic Epidemiology Network of Arteriopathy Study of the NHLBI Family Blood Pressure Program (FBPP). The hypertensive sibships were stratified by positive (+FH) or negative (-FH) family history of stroke. Genome-wide scans were repeated in each stratum, and the results were compared within each ethnic group by a regression-based analysis of heterogeneity.

Results--In whites, the best evidence for linkage was found on chromosome 16 in the unstratified sample of hypertensive sibpairs (logarithm of odds [LOD]=1.85 at 71 cM). In blacks, the best evidence for linkage was found on chromosome 2 in the unstratified sample of hypertensive sibpairs (LOD=1.95 at 230 cM). Additional evidence for linkage (LOD 1.5) was observed among white hypertensive sibpairs with a -FH on chromosome 13 and among black hypertensive sibpairs with a +FH of stroke on chromosome 19.

Conclusions--Significant evidence for linkage heterogeneity among hypertensive sibpairs stratified by family history of stroke suggests the presence of genes influencing susceptibility to both hypertension and stroke on chromosomes 13 (whites) and 19 (blacks). Although no significant evidence of heterogeneity was observed on chromosome 16 in whites and chromosome 2 in blacks, these chromosomes do provide evidence of linkage to hypertension.

Key words: hypertension • linkage (genetic) • stroke

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