New susceptibility locus for hypertension on chromosome 8q by efficient pedigree-breaking in an Italian isolate.
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 2,180-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.
Ciullo
Marina
M
Institute of Genetics and Biophysics, A. Buzzati-Traverso, CNR Naples, Italy. ciullo@igb.cnr.it
Bellenguez
Céline
C
Colonna
Vincenza
V
Nutile
Teresa
T
Calabria
Antonietta
A
Pacente
Rosalinda
R
Iovino
Gianluigi
G
Trimarco
Bruno
B
Bourgain
Catherine
C
Persico
M Graziella
MG
D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci