A genome wide scan for early onset primary hypertension in Scandinavians.
von Wowern F., Bengtsson K., Lindgren CM., Orho-Melander M., Fyhrquist F., Lindblad U., Råstam L., Forsblom C., Kanninen T., Almgren P., Burri P., Katzman P., Groop L., Hulthén UL., Melander O.
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.