1. The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives
- Author
-
Irene Pichler, Thomas Meitinger, Agatha Eisendle, Cristian Pattaro, Sara Pedrotti, Deborah Mascalzoni, Peter P. Pramstaller, Umberta Dal Cero, Alessandro De Grandi, Stefan A. Stefanov, Fabio Marroni, Christian J. Wiedermann, Martin Gögele, Alice Riegler, Florian D. Vogl, Clemens Egger, Christian Fuchsberger, Gerd K. Pinggera, and Claudia B. Volpato
- Subjects
Male ,Candidate gene ,lcsh:Internal medicine ,lcsh:QH426-470 ,Genetic Linkage ,Population ,Quantitative Trait Loci ,iologic Research Design ,Pedigree chart ,Biology ,Quantitative trait locus ,methods ,Genetics ,Cluster Analysis ,Humans ,Genetics(clinical) ,Computer Simulation ,Genetic Predisposition to Disease ,education ,lcsh:RC31-1245 ,Genetics (clinical) ,Genetic association ,education.field_of_study ,epidemiology/genetics ,Data Collection ,Genetic Diseases, Inborn ,Heritability ,Pedigree ,lcsh:Genetics ,Inborn ,Genetics, Population ,Genetic epidemiology ,Italy ,Genetic Diseases ,Epidemiologic Research Design ,Population study ,epidemiology ,Female ,Lod Score ,Cluster Analysis, Computer Simulation, Data Collection ,methods, Female, Genetic Diseases ,epidemiology/genetics, Genetic Linkage, Genetic Predisposition to Disease ,genetics, Genetics ,Population, Humans, Italy ,epidemiology, Lod Score, Male, Pedigree, Quantitative Trait Loci, iologic Research Design ,Demography ,Research Article - Abstract
Background There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries. Methods The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken. Results Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%. Conclusion The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.
- Published
- 2007