Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447-2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8-30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics

Determinants of further survival in centenarians from the province of Mantova

The MALVA project, one of the first Italian studies on population-based samples of centenarians, was addressed to the subjects aged 98+ residing in the province of Mantova (Northern Italy) at the 1st April 1998. The present study aims at analyzing the impact of selected clinical and socio-demographic variables on further survival of the 77 participants in the MALVA study.Adopting methods for multiple imputation of missing value, four distinct Cox regression models were estimated using groups of predefined variables describing sociodemographic characteristics, functional status, nutritional status, cardiovascular risk factors. Each model was adjusted for the effects of gender and age. Finally two complete models have been considered: the first one including the statistically significant variables in the previous analysis, and the second one obtained with a backward selection procedure. The variables included in the final models can be seen as markers of “frailty” or correlated conditions. Most of these variables maintained a significant influence on survival, however belonging to the “underweight” BMI category and being institutionalized emerged as the best “frailty” indicators in the centenarians from the province of Mantova. The results of this study are in agreement with several previous studies in recognizing that factors predicting mortality in centenarians are not the same well-known predictors of mortality in the middle-aged and younger elderly

The "Hidden frontier" between Trentino and Alto Adige: interaction between populations on the Roman-Germanic border

This study is part of the “Alteritas” project, which examines relationships between populations by identifying linguistic, bio-demographic, archaeological and cultural parameters of interaction, past and present. Using a multidisciplinary approach, we aim to analyze the complex interethnic relations in the language border zone between Trentino and Alto Adige. Adopting as a reference point the studies begun during the 1970s by J.W. Wolf and E.R. Cole on the “hidden frontier” in the Alta Val di Non (Upper Non Valley), our research extends to adjoining territories with comparable socio-economic situations. Considered in particular are the districts of the Alta Val di Non, lower Val di Fiemme and Bassa Atesina/Piana Rotaliana. Interaction between the communities is investigated considering aspects such as linguistic and cultural habits, traditions and social and economic structure, and migratory exchanges. The bio-demographic part of the project is aimed at identifying continuity/discontinuity in surname structure near the borders between Trentino and Alto Adige. Analysis of geographical distribution of surnames, considered as parameters of interaction, may help define the nature, means and degree of the relationships between populations. Telephone books and questionnaires provide the main data sources while marriage lists, where made available by the local institutions, offer further investigations. Questa ricerca si inserisce nel progetto "Alteritas", volto allo studio delle relazioni tra popolazioni mediante la individuazione di parametri di interazione (linguistici, biodemografici, archeologici e culturali) nella storia e nel presente. Lo studio intende analizzare, secondo un taglio multidisciplinare, le complesse relazioni interet¬niche nella zona di confine linguistico fra Trentino e Alto Adige. Prendendo come riferimento gli studi fatti a partire dagli anni '70 da J.W. Wolf e E.R. Cole sulla "Frontiera nascosta" nell'alta Val di Non, si estende il campo di indagine a territori contigui caratterizzati da contesti socio-economici comparabili. In particolare vengono presi in considerazione i distretti dell'Alta Val di Non, della bassa Val di Fiemme e della Bassa Atesina/Piana Rotaliana. Le interazioni tra comunità sono indagate considerando aspetti quali le abitudini linguistiche e culturali, i costumi e le strutture sociali ed economiche, gli scambi migratori. La parte biodemografica del progetto è finalizzata ad individuare continuità/discontinuità nella struttura per cognomi in prossimità delle aree di confine fra Trentino e Alto Adige. L'analisi della distribuzione geografica dei cognomi, considerati come parametro di interazione, può contribuire a definire la natura, le modalità e l'entità delle relazioni tra popolazioni. Le fonti di dati sono costituite da elenchi telefonici, questionari, e, come ulteriore approfondimento, subordinato alla disponibilità da parte degli enti preposti, liste di matrimoni

Chapitre 6. Patronymes et structure génétique de la République de Saint-Marin

On se propose dans cet article d’étudier la structure biodémographique et génétique de la République de Saint-Marin. Cet État séculaire présente la caractéristique d’être enclavé dans le territoire italien, de posséder avec ce dernier une frontière politico-administrative qui est restée inchangée pendant plus de cinq siècles et d’appliquer des règles particulières concernant le mariage avec les étrangers, pouvant limiter les échanges génétiques avec la population italienne voisine et influenc..

Patterns o f Gene Flow Inferred from Genetic Distances in the Mediterranean Region

The analysis of population structure may lead to inferences about demographic phenomena. In particular, regions of sharp genetic differentiation suggest the existence of factors that impaired gene flow and increased the evolutionary role of genetic drift. Here, we present an analysis of a data set of 10 allele frequencies in 39 populations of the Mediterranean region. As a preliminary step, we describe spatial patterns of allele frequencies using spatial autocorrelation analysis. We then construct a network connecting localities and estimate genetic distances along the edges of the network. By applying specific algorithms, we locate on the map the areas of sharpest genetic differentiation, or genetic boundaries. The main boundaries separate the northern and the southern coasts, especially in their western portions; in addition, several localities appear genetically isolated. The comparatively high genetic differentiation across the western Mediterranean, where the sea distances between localities are shorter, strongly suggests that the sea distance by itself can hardly be regarded as a major isolating factor among these populations. On the contrary, the decrease in genetic resemblance between populations of the 2 coasts as one proceeds westward may reflect an increased genetic exchange in the eastern Mediterranean basin or independent human dispersal along the 2 coasts or both

Arm measurements as determinants of further survival in centenarians

Being indicators of nutritional and functional status, anthropometric charactersmay have great prognostic signif- icance for survival at extremely advanced ages. For ethical and practical reasons however it is advisable to use characters such as armmeasurements easily measurable even in bedridden subjects. This study compares the in- fluence of some upper arm measurements and of Body Mass Index (BMI) on survival of the 77 subjects aged 98 years and over (98+) recruited within the MALVA project, one of the first Italian population-based studies on extremely old people. Adopting methods for multiple imputation of missing values, Gompertz regression models adjusted for gender and age were estimated for each anthropometric character or combination of char- acters, i.e. BMI;mid-upper armcircumference (MUAC)+ elbow breadth (EB)+ triceps skinfold thickness (TSF); corrected arm muscle area (CAMA). Being underweight and having a low CAMA and a low MUAC/high EB were positively associated with an increased risk of death, while no significant association was found with the condi- tion of being overweight/obese and the triceps skinfold thickness.When anthropometric variables were included in regression models along with covariates relating to nutritional and functional status, BMI and MUAC, but not CAMA, emerged as protective factors. It is suggested that MUAC can be recommended in evaluating the health status of extremely old people and that measuring EB may help to estimate the non-boney component of the arm

Gender, aging and longevity in humans: An update of an intriguing/neglected scenario paving the way to a gender-specific medicine

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene-environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases