Background: depression is widespread in the population, and one of the leading causes of disability, reduced life expectancy and mortality. Such a significant effect is based on the high frequency of comorbidity of depression with severe chronic somatic diseases. Genetic studies can provide tools to identify groups with a high level of genetic risk of comorbidity of these diseases in a population for their early specific prevention. The aim of review article was to justify the methodology and design of research directed for joint genetic risk markers for depression and chronic somatic diseases linked with each other in terms of genetic comorbidity. Publication, patients and methods: population cohort of depressive patients examined using international clinical and psychometric instruments. The study will allow: 1) to evaluate the risks of developing chronic somatic diseases in a population of patients with depression; 2) to assess the predictive power of polygenic risk scores of somatic diseases for symptoms of depression and somatic diseases in a population sample; 3) to validate polygenic risk scores for genetic comorbidity of depression and somatic diseases in a qualitatively described sample of patients using modern clinical and psychometric tools. Conclusion: the methodology and results of the study can be used for an evidence-based preventive approach in the field of mental and physical health.