Evaluating the context-dependent effect of family history of stroke in a genome scan for hypertension.
OBJECTIVE
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.


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 >or=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.
Morrison
Alanna C
AC
Human Genetics Center, University of Texas, Houston Health Science Center, 1200 Herman Pressler, Ste 453 E, Houston, TX 77030, USA. Alanna.C.Morrison@uth.tmc.edu
Brown
Andrew
A
Kardia
Sharon L R
SL
Turner
Stephen T
ST
Boerwinkle
Eric
E
D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics; D015992:Body Mass Index; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005192:Family Health; D005260:Female; D005796:Genes; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D008922:Mississippi / Q000453:epidemiology; D012307:Risk Factors; D018401:Sample Size; D035781:Siblings; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics; D013781:Texas / Q000453:epidemiology; D044465:White People / Q000235:genetics; D001741:Black or African American