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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.
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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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