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Human Molecular Genetics Advance Access originally published online on July 1, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 16 2077-2081
DOI: 10.1093/hmg/ddg206
© 2003 Oxford University Press

A genome wide scan for early onset primary hypertension in Scandinavians

Fredrik von Wowern1, Kristina Bengtsson1,2, Cecilia M. Lindgren1, Marju Orho-Melander1, Frej Fyhrquist3, Ulf Lindblad2, Lennart Råstam2, Carol Forsblom3, Timo Kanninen1, Peter Almgren1, Philippe Burri1, Per Katzman4, Leif Groop1, U. Lennart Hulthén1 and Olle Melander1,*

1Department of Endocrinology and 2Department of Community Medicine, Malmö University Hospital, SE-205 02, Malmö, Sweden, 3Department of Medicine, Division of Internal Medicine, Helsinki University Central Hospital, FI-00029, Helsinki, Finland and 4Department of Medicine, Hospital of Helsingborg, SE-251 87 Helsingborg, Sweden

Received May 12, 2003; Accepted June 15, 2003

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 ~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.

* To whom correspondence should be addressed at: Department of Endocrinology, Wallenberg Laboratory, Entrance 46, Floor 3, Malmö University Hospital MAS, SE-205 02, Malmö, Sweden. Tel: +46 40 336023; Fax: +46 40 337042; Email: olle.melander{at}endo.mas.lu.se


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