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Human Molecular Genetics Advance Access originally published online on April 12, 2006
Human Molecular Genetics 2006 15(10):1735-1743; doi:10.1093/hmg/ddl097
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© The Author 2006. Published by Oxford University Press. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact: journals.permissions@oxfordjournals.org

New susceptibility locus for hypertension on chromosome 8q by efficient pedigree-breaking in an Italian isolate

Marina Ciullo1,*, Céline Bellenguez2, Vincenza Colonna1, Teresa Nutile1, Antonietta Calabria1, Rosalinda Pacente1, Gianluigi Iovino3, Bruno Trimarco3, Catherine Bourgain2 and M. Graziella Persico1

1Institute of Genetics and Biophysics ‘A. Buzzati-Traverso’, CNR Naples, Italy, 2UMR 535 INSERM, University of Paris XI, Villejuif, France and 3Department of Clinical Medicine and Cardiovascular Sciences, University of Naples ‘Federico II’, Naples, Italy

* To whom correspondence should be addressed at: Institute of Genetics and Biophysics ‘A. Buzzati-Traverso’, CNR, Via Pietro Castellino, 111, 80131 Naples, Italy. Tel: +39 0816132251; Fax: +39 0816132595; Email: ciullo{at}igb.cnr.it

Received January 10, 2006; Accepted March 31, 2006

Essential hypertension (EH) affects a large proportion of the adult population in Western countries and is a major risk factor for cardiovascular diseases. EH is a multifactorial disease with a complex genetic component. To tackle the complexity of this genetic component, we have initiated a study of Campora, an isolated village in South Italy. A random sample of 389 adults was genotyped for a very dense microsatellite genome scan and phenotyped for EH. Of this sample, 173 affected individuals were all related through a 2180-member pedigree and could be integrated within a linkage analysis. The complexity of the pedigree prevented its direct use for a non-parametric linkage (NPL) analysis. Therefore, the method proposed by Falchi et al. [2004, Am. J. Hum. Genet., 75, 1015–1031] was used for automatic pedigree-breaking. We identified a new locus for EH on chromosome 8q22–23 and detected linkage with two known loci for EH: 1q42–43 and 4p16. Simulations showed that the linkage with 8q22–23 is highly genome-wide significant, even when accounting for the breaking of the pedigree. An extension to qualitative traits of another pedigree-breaking approach [Pankratz et al., 2001, Genet. Epidemiol., 21 (Suppl. 1), S258–S263] also detected a significant linkage on 8q22–23 using a remarkably different set of sub-pedigrees and helped to refine the location of the linkage signal. This work both identifies a new locus strongly linked to hypertension and shows that the power of linkage analysis can be improved by the appropriate use of efficient pedigree-breaking strategies.


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