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

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Abstract
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.