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Background: The present study investigates the feasibility of using three previously published genome-wide association studies (GWAS) results on blood lipids to develop polygenic risk scores (PRS) for population samples from the European part of the Russian Federation. Methods: Two population samples were used in the study - one from the Ivanovo region ( n = 1673) and one from the Vologda region ( n = 817). We investigated three distinct approaches to PRS development: using the straightforward PRS approach with original effect sizes and fine-tuning with PRSice-2 and LDpred2. Results: In total, we constructed 56 PRS scales related to four lipid phenotypes: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglyceride levels. Compared with previous results for the Russian population, we achieved an additional R 2 increase of 2-4%, depending on the approach and lipid phenotype studied. Overall, the R 2 PRS estimates approached those described for other populations. We also evaluated the clinical utility of blood lipid PRS for predicting carotid and femoral artery atherosclerosis. Specifically, we found that PRS for total cholesterol, low-density lipoprotein cholesterol, and triglycerides were positively correlated with ultrasound parameters of carotid and femoral artery atherosclerosis (ρ = 0.09-0.13, p < 0.001), whereas PRS for high-density lipoprotein cholesterol were inversely correlated with the number of plaques in the femoral arteries (ρ = -0.08, p = 8.71 × 10-3). Conclusions: PRS fine-tuning using PRSice-2 add LDpred2 improves the performance of blood lipid PRS. Our study demonstrates the potential for further use of blood lipid PRS for prediction of atherosclerosis risk.

To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3-V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis . NGS analysis was conducted at the family level. No significant differences between patient's groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota.