Development of an algorithm for determining of genetic risk at the primary healthcare level: a new tool for primary prevention

Family history is part of the medical history taken during preventive management of patients at model family medicine practices. Currently, it includes a one- (or two-) generational inquiry, mostly in terms of cardiovascular diseases, arterial hypertension and diabetes, but not genetics and/or family history of other diseases with probable genetic aetiology. Currently, there is no application based in algorithm available to doctors in Slovenia to determine the risk level for specific diseases for enhancing quality of work. As part of the study, an algorithm will be developed aimed at determining the risk level for the selected monogenic and polygenic diseases. The risk present among the Slovenian population for genetic diseases will be determined and clinical paths for acting when a certain risk level is present will be prepared. The results will be validated by a clinical genetic approach based on family pedigrees and the next-generation genetic sequencing method. The data will be collected in family medicine practices (N = 40). The sample will include healthy subjects presenting for preventive examinations (n=1,200). The following will be collected in the study: demographic data, three-generational family history for selected diseases, medical history of acquired and congenital risk factors for the selected diseases, and important clinical factors. Geneticists will develop an algorithm to assess genetic predisposition and validate the tool using real-life data. By means of the public health tool providing an assessment of family predisposition to the selected monogenic and polygenic diseases, we expect to contribute to an effective identification of people at increased risk for the selected diseases that constitute an important public health burden.

There is no public health tool or electronic application available to doctors or the lay public in Slovenia to determine the risk level for specific diseases with genetic aetiology to assess the risk level for cardiovascular diseases, hypertension, diabetes, cancer, neurological, mental and sensory diseases as well as other diseases present in the family with a possible genetic aetiology. The project results are expected to contribute significantly to the development of methodologies allowing for a practical risk assessment of (currently) healthy persons to evaluate their genetic predisposition, which is an important factor in the aetiology of complex – multifactorial genetic diseases. If a high risk for genetic diseases is identified, genetic counselling will follow, involving the validation of risk assessment obtained via the web tool, and then genetic testing. Genetic testing will be based on the next-generation sequencing method, which is currently the state-of-the-art method for diagnosing genetic diseases. The project will facilitate identification of individuals and families at increased genetic risk, which will contribute to better understanding of the epidemiology and extent of the health problem as well as open up new possibilities in the field of primary and secondary prevention.

In Slovenia, family doctors rarely include genetic aspects when treating patients, and they do not have any guidelines or clinical paths allowing for managing such patients and referring them to genetic management. The planned project will be contribute significantly to easier and, most of all, reliable identification of persons and families at high risk for common complex diseases: cardiovascular diseases, hypertension, diabetes, cancer, neurological, mental and sensory diseases and other diseases present in the family with a possible genetic aetiology. The above diseases constitute a global public health challenge. An early identification of persons at increased risk before they develop signs and symptoms of the disease may contribute significantly to the effective prevention of the disease and its consequences. The final validation of the effectiveness of the identification (specificity) of persons at high risk for monogenic diseases will be based on molecular genetic evidence of genetic predisposition.