Searching for genetic factors associated with early adult mortality in the Polish population using whole-exome sequencing

The aim of the project is to search for genetic variants predisposing to early death in the group of adults representative of the Polish population. The aim of the project is to answer the following questions: 1) What known genetic variants predisposing to early death are particularly common in the Polish population. What are the relative frequencies of each variant, and are there any variants that are currently underestimated in importance. 2) What new genetic variants (unknown mutations in genes with known function and mutations in genes not yet associated with diseases) occur in the Polish population, contributing to the early death of adults. Project results are expected to identify the most common genetic diseases contributing to early death among adults in Poland. With a high degree of probability, you can expect to find min. 10-20 cases of mutations with a clear effect and a clear relationship with the cause of death (previously described mutations, new destructive mutations in known genes). In addition, it is possible to identify new genes, the defects of which may cause serious, because they lead to early death, diseases in humans. Due to the representativeness of the WOBASZ cohort for the entire population of Poland, the results will allow to estimate the role of known rare diseases in adult mortality in our country. The results of the project may indicate the desirability of performing more extensive genetic tests for certain mutations in people with certain diseases than at present, or even the validity of screening the entire population. The emergence of new genes related to mortality is important for basic research in biology, physiology and medicine. The project is the first attempt to use WES in an epidemiological study in Poland. WES has been widely used in epidemiological studies in other countries, however, there are no reports on the use of this technology in the analysis of early mortality comparable to that described in the application.