Cardiovascular Disease Genetics and Multiomics Research Venue Report
On September 18, 2021, the China Heart Conference (CHC) 2021 "Cardiovascular Disease Genetics and Multiomics" will be held online.
Forum is sponsored by the Department of Epidemiology, Fuwai Hospital, Chinese Academy of Medical Sciences, and invites a number of top scholars in the field of cardiovascular disease genetic multi-omics research in my country to gather together, from the wide application of genome, transcriptome and proteomics data , The active exploration of metabolomics and microbiome data, and then the innovative attempt of multi-omics joint analysis, brought us a feast of knowledge about genetics big data and multi-omics research.
This sub-forum was co-hosted by Professor Lu Xiangfeng from Fuwai Hospital of Chinese Academy of Medical Sciences, Professor Yin Huiyong from Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, and Professor Chen Xiaowei from Institute of Molecular Medicine, Peking University.
Genetic big data and multi-omics integrated research on cardiovascular and other chronic diseases Integrated research. Professor Yang pointed out that most common human traits are often not regulated by a single gene, but by the environment and genes.
Genome-wide Association Study (GWAS) solves the problem of which sites are associated with diseases. However, there was a problem of heritability loss in the early stage of GWAS. Therefore, Professor Yang Jian provided a new research method in 2010, putting all SNPs in a mixed linear model to estimate all that it can explain Phenotypic variation. In addition, Professor Yang Jian also decomposed the genetic variation of from the genome level to the chromosome level to explore the relationship between chromosome length and heritability.
To sum up, Professor Yang Jian believes that there are many sites that affect the disease, and the effect of a single site is very small.On this basis, Professor Yang proposed an SMR analysis method to better identify candidate genes by integrating GWAS and eQTL. However, the integration of eQTL data requires consideration of time and space, and there are many difficulties in particular in terms of time. Similarly, other omics data can also be integrated, such as DNA methylation. Finally, Professor Yang Jian introduced us to the OPERA research method, which can integrate all genetic data on omics regulation. It was found that although there are some SNP sites that regulate multiple omics data, there are still independent phenomena in multiple omics. .
Cardiovascular clinical metabolomics research
China Pharmaceutical University Professor Qi Lianwen reported the basic concepts of cardiovascular clinical metabolomics research and shared the research progress of the team with us. The
report introduced that Professor Qi's team conducted a non-targeted metabolomics analysis of 2324 plasma clinical samples from multiple centers and discovered 125 differential metabolites related to coronary heart disease . Further mechanism studies revealed that N-acetylneuraminic acid (Neu5Ac), a metabolic marker related to the progression of coronary heart disease, acted as a signaling molecule to activate the Rho-ROCK pathway to trigger RhoA and Cdc42-dependent myocardial injury. Follow-up animal and cell experiments proved Silencing neuraminidase-1 can effectively alleviate myocardial ischemic injury. Drug research found that the antiviral drugs oseltamivir and zanamivir, as inhibitors of neuraminidase-1, can significantly increase the 24-hour survival rate of myocardial ischemia rats, and significantly improve related indicators; Chinese medicine library screening found that new candidate salvianolic acid drug can inhibit neuraminidase, and it can also be used to treat ischemic cardiovascular and cerebrovascular diseases in the future; the original innovative drug C-09 is also gradually being optimized and transformed, and it is expected to be used in future cardiovascular diseases the treatment. The relevant results provide new targets for the research and development of coronary heart disease drugs, and also open up new ideas for the repositioning of old drugs that have already been on the market.
Professor Qi Lianwen presented us with a complete metabolomics research example, from the screening of metabolic differences,It is very exciting to study the animal mechanism, and then to the later drug discovery and clinical transformation.
intestinal flora and bile acid 's role in metabolic vascular diseases The microflora has a bridging role in organ interaction and common pathogenesis of metabolic diseases.
In the report, Professor Jiang introduced the intestinal flora in the human body as a new organ and bridge that connects the human body and the external environment, and can perceive changes in small molecular substances such as lipids caused by the external environment such as drugs, diet, and exercise. Polysaccharides, LPS , short-chain fatty acids, bile acids, etc., further cause changes in host metabolism. Through clinical cohort and animal experiments, it was found that intestinal FXR was positively correlated with intestinal ceramide in both mice and humans. Subsequent screening of intestinal ceramide-related metabolic pathways and gene expression revealed that SMPD3 is its main metabolic pathway. Several large cohorts have found that ceramide is an independent risk factor for cardiovascular events. The mechanism is to directly induce the abnormal function of endothelial cells and increase the synthesis of macrophage cytokines. Animal experiments have found that intestinal FXR-specific knockout can reduce atherosclerosis by inhibiting the SMPD3-ceramide axis, suggesting that intestinal FXR, SMPD3 and ceramide play an important role in the pathogenesis of atherosclerosis.
The research of Professor Jiang's team revealed that the intestinal flora-bile acid-intestinal FXR/TGR5 axis regulates metabolic diseases, showing the bridge role of intestinal flora in metabolic diseases.
Microbiology research driven by data and methods
Institute of Microbiology, Chinese Academy of Sciences Professor Jun Wang, a researcher of data-driven microbiome research and its relationship with human health,It also described the research direction and innovation of the team.
first combines the intestinal metagenomics and cardiovascular disease, focusing on the intestinal flora to increase the level of trimethylamine oxide in the circulatory system through the metabolism of carnitine, which leads to atherosclerosis and coronary artery disease. The increased risk of heart disease is an independent risk factor and treatment target for the occurrence and development of the disease. Secondly, Professor Wang introduced that the team has promoted the application of third-generation sequencing technology (SMRT) and the establishment of a third-generation sequencing technology platform, and has made contributions to the development of next-generation sequencing technology. Optimized the method for the enrichment and sequencing of virus particles in the intestinal metagene, speeding up the detection process, and realizing sample collection and detection analysis within one day. The new detection method further tested the enterovirus particles of patients with new coronary pneumonia , and found that there were differences in enterovirus particles between patients with new coronary pneumonia and healthy people, and there were also differences in enterovirus particles between severe and mild patients. In the future, we will analyze the role of intestinal commensal viruses in innate immunity and metabolome, and explore the role of intestinal commensal viruses as part of the intestinal metagenomics in the occurrence and development of diseases.
Professor Jun Wang showed us the cutting-edge progress of microbiome research, and proposed to increase cooperation to promote the research progress of the association between GWAS and gut microbes in the Chinese population, and show the future research direction of intestinal metagenomics and the development of human diseases.
A population study of multiomics and cardiovascular and metabolic risk factors
Professor Sun Liang from the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences introduced the role of multiomics in cardiovascular and metabolic risk factors from the perspective of nutritional epidemiology Population research progress.
The dietary risk factors for death from cardiovascular and metabolic diseases mainly include excessive sodium intake and insufficient intake of fruits, n-3 fatty acids, vegetables and whole grains. In order to solve the world problem of how to promote health through diet, the concept of precise nutrition has been proposed internationally, and the realization of this vision requires the application of multi-omics and wearable devices.
Professor Sun’s research group has established a cohort of 3,000 people since 2005, collecting data on environmental factors, genetics, molecular phenotypes, and diseases.Lay a solid foundation for the development of precision nutrition research. First of all, in terms of genomics research, the team of associate researcher Sun Liang found that diet and genetic risk score (GRS) are significantly related to blood cholesterol. With the increase of GRS, the effect of dietary cholesterol on blood cholesterol increases. This finding suggests The importance of dietary intervention based on genetic risk. Second, in terms of metabolomics research, Professor Sun's research group established the largest acylcarnitine database and lipidome database in Asia. Carnitine is a necessary cofactor for the β-oxidation process of long-chain fatty acids, and acyl carnitine is its metabolite. The team found that the combination of traditional risk factors and specific plasma acylcarnitines can increase the predictive effect of diabetes by 17%. Further network analysis found that long-chain n-6 fatty acids have a protective effect on metabolic syndrome, and this effect is in The short-medium chain acylcarnitine is fortified when the level is low. In addition, the research team also found that 11 new sphingolipids can significantly increase the risk of type 2 diabetes. At the same time, through Mendel randomization, they have discovered the types of sphingolipids that are causally related to type 2 diabetes, which are expected to serve as new intervention targets. .
Finally, Professor Sun shared the new findings of dietary intervention and microbiome research. For example, peanut intervention can increase the metabolic syndrome reversal rate while reducing baseline body weight, and the intestinal flora structure found through machine learning can predict the effect of peanut intervention. In addition, the team also found that low-carbohydrate diets can increase the level of HDL-C that is beneficial to the body while reducing weight. Further analysis of metagenomic and metabolome found that the flora CAG network, fatty acids and acyl meat The changes of alkali are all related to the improvement of blood lipids, and the changes of CAG contribute the most to the improvement of blood lipids.
In summary, through multi-omics and population studies, the research results of Professor Sun’s team provide new insights into the relationship between dietary intervention, microbial structure, body metabolism characteristics, and cardiovascular and metabolic diseases. Provide scientific basis for precise nutrition and chronic disease prevention and control.
Through this forum, experts introduced the latest research technologies and results in the fields of genetics and multi-omics of cardiovascular and metabolic diseases.From the perspectives of genomics, metabolomics and metagenomics, they shared the research strategies and latest developments of each team. The content is rich. I hope that fellow colleagues and graduate students participating in this forum will be inspired and harvested to jointly promote the further development of this field.
Zhao Kun, Liu Mengyao, Shapikatijiang, Liu Bisen
Click on " Read the original " to enter the conference microsite
(Source: Heart Conference)
Click to share _
img9 img click collection
.
