Whole-Exome Sequencing in the Isolated Populations of Cilento from South Italy.

The present study describes the genetic architecture of the isolated populations of Cilento, through the analysis of exome sequence data of 245 representative individuals of these populations. By annotating the exome variants and cataloguing them according to their frequency and functional effects, we identified 347,684 variants, 67.4% of which are rare and low frequency variants, and 1% of them (corresponding to 319 variants per person) are classified as high functional impact variants; also, 39,946 (11.5% of the total) are novel variants, for which we determined a significant enrichment for deleterious effects. By comparing the allele frequencies in Cilento with those from the Tuscan population from the 1000 Genomes Project Phase 3, we highlighted an increase in allele frequency in Cilento especially for variants which map to genes involved in extracellular matrix formation and organization. Furthermore, among the variants showing increased frequency we identified several known rare disease-causing variants. By different population genetics analyses, we corroborated the status of the Cilento populations as genetic isolates. Finally, we showed that exome data of Cilento represents a useful local reference panel capable of improving the accuracy of genetic imputation, thus adding power to genetic studies of human traits in these populations.

Body composition, leg length and blood pressure in a rural Italian population: a test of the capacity-load model.

BACKGROUND AND AIMS: Whereas adult weight or body mass index (BMI) are directly associated with blood pressure (BP), birth weight is inversely associated with BP. The scenario for height is more complex, as both tall and short stature have been associated with higher BP. We used a theoretical model treating sitting height (SH) and tissue masses (fat mass, lean mass) as components of metabolic load, and leg length (LL) as a marker of homeostatic metabolic capacity. We predicted that decreased capacity and increased load would be independently associated with increased BP.. METHODS AND RESULTS: Anthropometry, body composition (bio-electrical impedance analysis) and BP were measured in 601 adults (228 male) aged 20-91 years from three hill villages in southern Italy. Multiple regression analysis was used to investigate associations of body composition and anthropometry with BP. Adjusting for age, systolic BP (SBP) was associated with lean mass in males, and with adiposity in females, whereas diastolic BP (DBP) was associated with fat mass in both sexes. Associations of LL and SH with BP were in opposite directions. LL was inversely associated with SBP and DBP in males, with a similar trend evident in females. SH was directly associated with SBP and DBP in females, and with DBP in males. CONCLUSIONS: Consistent with our theoretical model, metabolic load is associated with increased BP, though differently between the sexes, whereas metabolic capacity is independently associated with lower BP. Our findings suggest that early growth improves hemodynamic tolerance of high metabolic load in adulthood..

Meta-analysis of genome-wide association studies for personality.

Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17,375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ≈ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10(-8) and 3.1 × 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10(-8)). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking.

The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N=7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P=2 × 10(-8)). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed α-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N=5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders.

Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MetSyn) is associated with an increased risk of atherosclerosis and fatal cardiovascular events. Angiogenesis is thought to contribute to this risk as it might be involved in the progression of atherosclerotic plaques. We investigated the levels of circulating biomarkers of angiogenesis and cardiovascular risk in adults with MetSyn and assessed their association with established metabolic risk factors. DESIGN: The Genetic Park project is a highly inclusive cross-sectional survey (about 80% of residents) conducted in three isolated populations in Southern Italy. A total of 1000 men and women (age range: 18-98 years) were included in the analysis. Anthropometric and blood pressure measurements were recorded. Metabolic and cardiovascular biomarkers included glucose, triglycerides, total cholesterol, HDL, vascular endothelial growth factor, placental growth factor (PlGF), soluble fms-like tyrosine kinase-1, high-sensitivity C-reactive protein, high-sensitivity troponin T (hs-TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULT: Subjects with MetSyn had higher levels of PlGF and NT-proBNP after adjustment for age, smoking and body mass index. Circulating levels of PlGF, hs-TnT and NT-proBNP were directly related to the number of criteria of MetSyn, and this association interacted with gender. There was a strong correlation between ageing and cardiovascular risk. CONCLUSIONS: The increase in circulating levels of biomarkers of angiogenesis and cardiac function in subjects with MetSyn mirrors the pathophysiological changes occurring in the cardiovascular system. Over time, these changes might accelerate the formation and progression of atherosclerotic plaques and contribute significantly to cardiovascular morbidity and mortality risk.

[Pirenzepina as an inhibitor of gastric secretion (experimental research)]. / La pirenzepina farmaco inibitore della secrezione gastrica.

Experimental research has shown that pirenzepina possesses interesting inhibiting properties with respect to gastric secretion and the formation of experimentally induced gastric ulcers.

[Experimental analysis of the immunizing and protective action of an association of total bacterial antigens]. / Analisi sperimentale del potere immunizzante e protettore di una associazione di antigeni batterici totali.

The A. by a series of experimental works have shown that an association of total bacteria antigens (SPRE) administered in the rabbit vai intramuscular route or by inhalation is able to cause the appearance of serum specific antibodies and to have a significant protective action.