Published online before print November 8, 2004, doi: 10.1161/01.HYP.0000148994.89903.fa
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(Hypertension. 2004;44:872.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Genome-Wide Scan for Blood Pressure Suggests Linkage to Chromosome 11, and Replication of Loci on 16, 17, and 22
From the Twin Research and Genetic Epidemiology Unit (M.d.L., T.D.S., T.A.), St. Thomas’ Hospital, London, UK; and Department of Medical Epidemiology and Biostatistics (M.d.L.), Karolinska Institutet, Stockholm, Sweden.
Correspondence to Marlies de Lange, Twin Research and Genetic Epidemiology Unit, St. Thomas’ Hospital, Lambeth Palace Rd, London SE1 7EH, UK. E-mail marlies.deLange{at}meb.ki.se
Hypertension was one of the first complex traits to be studied and is thought to be influenced by polygenic and multiple environmental risk factors. Several genomic studies have found suggestive logarithm of odds (LOD) scores for either blood pressure or essential hypertension, but few loci have been replicated. In this study, we performed a genome-wide linkage analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP) on 1109 white female dizygotic twin pairs from the TwinsUK registry in London. Multipoint linkage analysis replicated the locations of 3 previously reported linkage peaks: on chromosome 16 at 65 cM (LOD 0.8 for SBP and 1.8 for DBP); on chromosome 17 at 70 cM (LOD 1.8 SBP); and at 35 cM on chromosome 22 (LOD 0.97 SBP and 0.99 DBP). Results from multipoint analysis showed 1 novel suggestive linkage for SBP (multipoint LOD 2.28; 2-point P=0.0007) at 35 cM on chromosome 11. Results were similar when those on blood pressure medication were excluded. These are encouraging results for hypertensive research and demonstrate that despite past disappointments, linkage studies can be used to replicate regions from other studies and potentially discover new genetic risk factors of moderate to large effect size. Considering the differences in selection and ascertainment of the previous linkage studies, these results also suggest that some quantitative trait loci are likely to influence the normal range of blood pressure and clinical hypertension, whereas others will be specific to each trait. Future studies should focus on the fine mapping of these replicated regions, which include potential candidate genes.
Key Words: genetics • linkage analysis • blood pressure • twins
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