Journal Article

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

Marina Ciullo, Céline Bellenguez, Vincenza Colonna, Teresa Nutile, Antonietta Calabria, Rosalinda Pacente, Gianluigi Iovino, Bruno Trimarco, Catherine Bourgain and M. Graziella Persico

in Human Molecular Genetics

Volume 15, issue 10, pages 1735-1743
Published in print May 2006 | ISSN: 0964-6906
Published online April 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl097

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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.

Journal Article.  6567 words.  Illustrated.

Subjects: Genetics and Genomics

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