2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease 0
the genome (average marker spacing of 3 .6cM) . The heritability for
VEGF serum levels was estimated to 0 .86 after adjusting for age .
To perform linkage analysis we broke the large genealogy using
GREFFA method through a multiple splitting approach recently proposed
by Bellenguez and coll .
With the regression-based linkage statistic, we detected a strong linkage
on chromosome 6p12 .3 (LOD=10 .08) at marker D6S459 . This
linkage signal exactly corresponds to the location of the VEGF gene .
Hence, coding and regulatory regions of VEGF gene were sequenced
in a sample of 42 individuals. 31 polymorphisms were identified, 22 of
which having a MAF>0 .05 .
The association between these 22 SNPs and VEGF levels was tested
using GTAM test, that also corrects for relatedness between individuals
through the genealogical information . After correction for the number
of independent tests performed, significant association was detected
with two SNPs (p