A genome wide scan for early onset primary hypertension in Scandinavians.
With the aim of identifying hypertension susceptibility loci, we performed a genome wide scan in Scandinavian sib-pairs with early onset primary hypertension. To be classified as affected, a diagnosis of primary hypertension at age </=50 years was required. Two hundred and forty three patients with onset of primary hypertension at 40.0+/-7.7 (mean+/-SD) years from 91 families (91 sib-ships with a mean of 2.7 and a range of 2-6 affected members per sib-ship) were genotyped with 362 microsatellite markers with a density of approximately 10 cM. Loci obtaining nominal P</=0.016 (LOD score >/= 1.0) were fine mapped with additional markers. Multipoint non-parametric linkage analysis was performed using GENEHUNTER v 2.0. Using simulations, a nominal P</=0.0002 was determined to be a genome wide significant evidence of linkage. In the 10 cM genome wide scan, nominal P</=0.016 were found on chromosomes 1 at 81 cM (P=0.007), 2 at 115 cM (P=0.006), 3 at 108 cM (P=0.006), 14 at 45 cM (P=0.0002) and at 99 cM (P=0.001), 17 at 42 cM (P=0.015) and 19 at 89 cM (P=0.007). After fine mapping of these loci, one of the chromosome 14 loci just obtained the level of genome wide significance (P=0.0002 at 41 cM) and the chromosome 2 locus reached suggestive evidence of linkage (P=0.002 at 118 cM). Our data suggest a hypertension susceptibility locus on chromosome 14 around 41 cM. The locus on chromosome 2 is also promising as it has been implicated in hypertension and blood pressure regulation in earlier genome scans.
von Wowern
Fredrik
F
Department of Endocrinology, Malmö University Hospital, SE-205 02, Malmö, Sweden.
Bengtsson
Kristina
K
Lindgren
Cecilia M
CM
Orho-Melander
Marju
M
Fyhrquist
Frej
F
Lindblad
Ulf
U
Råstam
Lennart
L
Forsblom
Carol
C
Kanninen
Timo
T
Almgren
Peter
P
Burri
Philippe
P
Katzman
Per
P
Groop
Leif
L
Hulthén
U Lennart
UL
Melander
Olle
O
D000328:Adult; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009664:Norway; D035781:Siblings; D013548:Sweden
D005819:Genetic Markers