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ABSTRACT: Hypertension represents a major cause of cardiovascular morbidity and mortality worldwide but its prevalence has been shown to vary in different countries. The reasons for such differences are still matter of debate, the relative contributions given by environmental and genetic factors being still poorly defined. We estimated the current prevalence, distribution and determinants of hypertension in isolated Sardinian populations and also investigated the environmental and genetic contribution to hypertension prevalence taking advantage of the characteristics of such populations.
An epidemiological survey with cross-sectional design was carried out measuring blood pressure in 9845 inhabitants of 10 villages of Ogliastra region between 2002 and 2008. Regression analysis for assessing blood pressure determinants and variance component models for estimating heritability were performed. Overall 38.8% of this population had hypertension, its prevalence varying significantly by age, sex and among villages taking into account age and sex structure of their population. About 50% of hypertensives had prior cardiovascular disease. High blood pressure was independently associated with age, obesity related factors, heart rate, total cholesterol, alcohol consumption, low education and smoking status, all these factors contributing more in women than in men. Heritability was 27% for diastolic and 36% for systolic blood pressure, its contribution being significantly higher in men (57%) than in women (46%). Finally, the genetic correlation between systolic and diastolic blood pressure was 0.74, indicating incomplete pleiotropy.
Genetic factors involved in the expression of blood pressure traits account for about 30% of the phenotypic variance, but seem to play a larger role in men; comorbidities and environmental factors remain of predominant importance, but seem to contribute much more in women.
PLoS ONE 01/2013; 8(3):e59612. · 4.09 Impact Factor
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ABSTRACT: This study aimed at estimating the prevalence of osteoporosis and osteopenia in a Sardinian isolated population using hand quantitative ultrasound and at investigating the associated factors. The authors utilized a subset of data from a large population-based epidemiologic survey carried out in the Ogliastra region of Sardinia between 2003 and 2008. The sample consists of 6,326 men and women aged ≥30 years, who underwent quantitative ultrasound at the phalanges, bioelectrical impedance, anthropometric measurements, blood tests, and a standardized epidemiologic questionnaire collecting sociodemographic, lifestyle, medical, physiologic, and pharmacologic data. The T-score thresholds for amplitude-dependent speed of sound of -3.2 standard deviations and between -3.2 and -1 standard deviations were used to diagnose osteoporosis and osteopenia, respectively. Prevalence of osteoporosis was 17.0% in women and 5.2% in men. Logistic regression analysis revealed that factors associated with osteoporosis were age, anthropometric and bioimpedance measures, alkaline phosphatase levels, and menopause in women. High education, exercise, and beer consumption seem to be protective factors, whereas a family history of osteoporosis is a risk factor. Results show that osteoporosis in this population is comparable with that found in different countries, suggesting that quantitative ultrasound could be used more widely to detect high-risk individuals for preventing osteoporotic fractures.
American journal of epidemiology 06/2011; 174(4):432-9. · 5.59 Impact Factor
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Ginevra Biino,
Laura Casula,
Francesca de Terlizzi, Mauro Adamo,
Simona Vaccargiu,
Marcella Francavilla,
Davide Loi,
Alberto Casti,
Manuela Atzori,
Massimiliano Cosso,
Francesca Marras,
Chiara Cepollaro,
Maria Luisa Brandi,
Mario Pirastu
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ABSTRACT: It is now recognized that quantitative ultrasound (QUS) measures may predict osteoporotic fracture risk independently of bone mineral density. Although many studies have examined genetic and environmental components of bone mineral density and calcaneal QUS measures, few of them were addressed to phalangeal QUS phenotypes, and none to graphic trace parameters. This study aims to evaluate the relative contribution of genetics in the expression of phalangeal QUS traits in the adult healthy population of a Sardinian genetic isolate. Our sample includes 6056 men and women aged 30-103 years, from 43 extended pedigrees recruited in 10 villages of Ogliastra region in occasion of a large epidemiologic survey. Amplitude-dependent speed of sound (AD-SoS), fast wave amplitude (FWA), signal dynamic (SDy), bone transmission time (BTT) and ultrasound bone profile index (UBPI) were obtained from the non-dominant hand using the IGEA DBM Sonic Bone Profiler. These phenotypes were first regressed on age, anthropometric and bioimpedance measures, serum calcium, phosphorus and alkaline phosphatase, alcohol and caffeine consumption, smoking status, exercise and also months since menopause and estrogens use in women. Adjusted QUS parameters were then analyzed by univariate and bivariate variance component models to obtain heritability estimates and genetic and environmental correlations. QUS parameters were correlated to age, anthropometric and bioimpedance measures, serum phosphorus, alkaline phosphatase and to reproductive history and menopause in women. All phenotypes demonstrated substantial heritabilities ranging from 0.29+/-0.03 for SDy to 0.55+/-0.03 for FWA. Proportion of variance due to all covariates ranged from 36% for SDy to 59% for BTT. Many significant genetic and environmental correlations were found between the different QUS measures. In this study, genetic factors appear to play a relevant role in determining hand QUS measures even when taking into account various important environmental factors. Furthermore, the modest genetic correlations may imply the existence of partially unique sets of genes affecting different QUS traits, thus suggesting that QUS parameters measure different properties of bone tissue.
Bone 12/2009; 46(4):1197-203. · 4.02 Impact Factor
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Evelina Mocci,
Maria P Concas,
Manuela Fanciulli,
Nicola Pirastu, Mauro Adamo,
Valentina Cabras,
Cristina Fraumene,
Ivana Persico,
Alessandro Sassu,
Andrea Picciau,
Dionigio A Prodi,
Donatella Serra,
Ginevra Biino,
Mario Pirastu,
Andrea Angius
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ABSTRACT: A multiplicity of study designs such as gene candidate analysis, genome wide search (GWS) and, recently, whole genome association studies have been employed for the identification of the genetic components of essential hypertension (EH). Several genome-wide linkage studies of EH and blood pressure-related phenotypes demonstrate that there is no single locus with a major effect while several genomic regions likely to contain EH-susceptibility loci were validated by multiple studies.
We carried out the clinical assessment of the entire adult population in a Sardinian village (Talana) and we analyzed 16 selected families with 62 hypertensive subjects out of 267 individuals. We carried out a double GWS using a set of 902 uniformly spaced microsatellites and a high-density SNPs map on the same group of families.
Three loci were identified by both microsatellites and SNP scans and the obtained linkage results showed a remarkable degree of similarity. These loci were identified on chromosome 2q24, 11q23.1-25 and 13q14.11-21.33. Further support to these findings is their broad description present in literature associated to EH or related phenotypes. Bioinformatic investigation of these loci shows several potential EH candidate genes, several of whom already associated to blood pressure regulation pathways.
Our search for major susceptibility EH genetic factors evidences that EH in the genetic isolate of Talana is due to the contribution of several genes contained in loci identified and replicated by earlier findings in different human populations.
BMC Medical Genetics 02/2009; 10:81. · 2.33 Impact Factor
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Dionigio Antonio Prodi,
Nicola Pirastu,
Giuseppe Maninchedda,
Alessandro Sassu,
Andrea Picciau,
Maria Antonietta Palmas,
Alessandra Mossa,
Ivana Persico, Mauro Adamo,
Andrea Angius,
Mario Pirastu
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ABSTRACT: Androgenetic alopecia (AGA) is a common heritable polygenic disorder whose genetics is not fully understood, even though it seems to be X-linked. We carried out an epidemiological survey for AGA on 9,000 people from 8 isolated villages of a secluded region of Sardinia (Ogliastra), and identified a large cohort of affected individuals. We genotyped 200 cases and 200 controls (mean kinship 0.001) with the 500k chip array and conducted case-control association analysis on the X chromosome. We identified Xq11-q12 as strongly associated with AGA. In particular, we found that rs1352015 located 8 kb from the EDA2R gene showed the best result (P=7.77e(-7)). This region also contains the AR gene, hence we tested both genes in 492 cases and 492 controls. We found that the non-synonymous SNP rs1385699 on EDA2R gave the best result (P=3.9e(-19)) whereas rs6152 on the AR gene is less significant (P=4.17e(-12)). Further statistical analysis carried out by conditioning each gene to the presence of the other showed that the association with EDA2R is independent while the association with AR seems to be the result of linkage disequilibrium. These results give insight into the pathways involved in AGA etiology.
Journal of Investigative Dermatology 05/2008; 128(9):2268-70. · 6.31 Impact Factor
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ABSTRACT: In our studies of genetically isolated populations in a remote mountain area in the center of Sardinia (Italy), we found that 80-85% of the inhabitants of each village belong to a single huge pedigree with families strictly connected to each other through hundreds of loops. Moreover, intermarriages between villages join pedigrees of different villages through links that make family trees even more complicated. Unfortunately, none of the commonly used pedigree drawing tools are able to draw the complete pedigree, whereas it is commonly accepted that the visual representation of families is very important as it helps researchers in identifying clusters of inherited traits and genotypes. We had a representation issue that compels researchers to work with subsets extracted from the overall genealogy, causing a serious loss of information on familiar relationships. To visually explore such complex pedigrees, we developed PedNavigator, a browser for genealogical databases properly suited for genetic studies.
The PedNavigator is useful for genealogical research due to its capacity to represent family relations between persons and to make a visual verification of the links during family history reconstruction. As for genetic studies, it is helpful to follow propagation of a specific set of genetic markers (haplotype), or to select people for linkage analysis, showing relations between various branch of a family tree of affected subjects.
PedNavigator is an application integrated into a Framework designed to handle data for human genetic studies based on the Oracle platform. To allow the use of PedNavigator also to people not owning the same required informatics infrastructure or systems, we developed PedNavigator Lite with mainly the same features of the integrated one, based on MySQL database server. This version is free for academic users, and it is available for download from our site http://www.shardna.com.
BMC Bioinformatics 01/2006; 6 Suppl 4:S17. · 2.75 Impact Factor
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ABSTRACT: Abstract
Background
In our studies of genetically isolated populations in a remote mountain area in the center of Sardinia (Italy), we found that 80–85% of the inhabitants of each village belong to a single huge pedigree with families strictly connected to each other through hundreds of loops. Moreover, intermarriages between villages join pedigrees of different villages through links that make family trees even more complicated. Unfortunately, none of the commonly used pedigree drawing tools are able to draw the complete pedigree, whereas it is commonly accepted that the visual representation of families is very important as it helps researchers in identifying clusters of inherited traits and genotypes. We had a representation issue that compels researchers to work with subsets extracted from the overall genealogy, causing a serious loss of information on familiar relationships.
To visually explore such complex pedigrees, we developed PedNavigator, a browser for genealogical databases properly suited for genetic studies.
Results
The PedNavigator is useful for genealogical research due to its capacity to represent family relations between persons and to make a visual verification of the links during family history reconstruction. As for genetic studies, it is helpful to follow propagation of a specific set of genetic markers (haplotype), or to select people for linkage analysis, showing relations between various branch of a family tree of affected subjects.
Availability
PedNavigator is an application integrated into a Framework designed to handle data for human genetic studies based on the Oracle platform. To allow the use of PedNavigator also to people not owning the same required informatics infrastructure or systems, we developed PedNavigator Lite with mainly the same features of the integrated one, based on MySQL database server. This version is free for academic users, and it is available for download from our site http://www.shardna.com.
BMC Bioinformatics. 01/2005;
