Within Ogliastra Project, a large survey conducted in an isolated Sardinian population, we present results of an epidemiological study and of a GWS on blood pressure in Talana village (1200 inhabitants). This population may provide significant power to the identification of QTLs due to slow demographic growth, high endogamy and inbreeding, reduced genetic heterogeneity, low number of founders, stable culture and accurate genealogical records. Genotyping was carried out on 875 volunteers by a total of 654 informative markers (average het 0.71,SD=0.09) distributed over the genome (NHLBI Mammalian Genotyping Service). So far 355 individuals have undergone an extensive evaluation comprehensive of physical examination, serological analyses, anthropometrical and blood pressure measurements according to the British Hypertension Society protocol, structured interviews to collect living habits, exposure to most common risk factors, medical and medication history, information about familial disorders. Mean age is 53±19 years (55% females), SBP and DBP are normally distributed (p<0.05) with average of 135±20 and 80±10 mmHg respectively. Regression models were performed to find associated variables accounting for environmental factors. To retain power and information inherent to large pedigrees, all 355 subjects were included in 3 big inbred families (mean size 283,n=850,55% genotyped). Using SOLAR, a genome-wide linkage analysis by variance components approach was conducted including all significative covariates: sex, age, alcohol assumption and anti-hypertensive therapy for SBP; sex, BMI, total cholesterol, LDL, alcohol assumption and anti-hypertensive therapy for DBP. Heritability of SBP and DBP was 0.21 (P=0.019) and 0.25 (P=0.005) respectively, indicating that a substantial portion of trait variation is attributable to genetic factors. Suggestive linkage evidence for DBP was found on chromosomes 1 (LOD 2.02) and 9 (LOD 2.28). We observed LOD>1.7 on chromosomes 2, 4, 6, 10 and 19 for DBP. No significant LOD score for SBP was obtained. Supported by grants from Telethon, Italy No.E1185
Genome Wide Scan for blood pressure in an isolated Sardinian founder population
A Angius;G Biino;M Pirastu
2003
Abstract
Within Ogliastra Project, a large survey conducted in an isolated Sardinian population, we present results of an epidemiological study and of a GWS on blood pressure in Talana village (1200 inhabitants). This population may provide significant power to the identification of QTLs due to slow demographic growth, high endogamy and inbreeding, reduced genetic heterogeneity, low number of founders, stable culture and accurate genealogical records. Genotyping was carried out on 875 volunteers by a total of 654 informative markers (average het 0.71,SD=0.09) distributed over the genome (NHLBI Mammalian Genotyping Service). So far 355 individuals have undergone an extensive evaluation comprehensive of physical examination, serological analyses, anthropometrical and blood pressure measurements according to the British Hypertension Society protocol, structured interviews to collect living habits, exposure to most common risk factors, medical and medication history, information about familial disorders. Mean age is 53±19 years (55% females), SBP and DBP are normally distributed (p<0.05) with average of 135±20 and 80±10 mmHg respectively. Regression models were performed to find associated variables accounting for environmental factors. To retain power and information inherent to large pedigrees, all 355 subjects were included in 3 big inbred families (mean size 283,n=850,55% genotyped). Using SOLAR, a genome-wide linkage analysis by variance components approach was conducted including all significative covariates: sex, age, alcohol assumption and anti-hypertensive therapy for SBP; sex, BMI, total cholesterol, LDL, alcohol assumption and anti-hypertensive therapy for DBP. Heritability of SBP and DBP was 0.21 (P=0.019) and 0.25 (P=0.005) respectively, indicating that a substantial portion of trait variation is attributable to genetic factors. Suggestive linkage evidence for DBP was found on chromosomes 1 (LOD 2.02) and 9 (LOD 2.28). We observed LOD>1.7 on chromosomes 2, 4, 6, 10 and 19 for DBP. No significant LOD score for SBP was obtained. Supported by grants from Telethon, Italy No.E1185I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
