- A phenomics-based approach for the detection and interpretation of shared genetic influences on 29 biochemical indices in southern Chinese men. - However, few studies have reported on the systematic mining of shared genetics among clinical biochemical indices based on phenomics methods, especially in China. - This study aimed to apply phenomics to systematically explore shared genetics among 29 biochemical indices based on the Fangchenggang Area Male Health and Examination Survey cohort.. - Result: A total of 1999 subjects with 29 biochemical indices and 709,211 single nucleotide polymorphisms (SNPs) were subjected to phenomics analysis. - The results showed that 29 biochemical indices were from a network. - IgA, IgG, IgE, IgM, HCY, AFP and B12 were in the central community of 29 biochemical indices. - Key genes and loci associated with metabolism traits were further identified, and shared genetics analysis showed that 29 SNPs ( P <. - 10 − 4 ) were associated with three or more traits. - After integrating the SNPs related to two or more traits with the GWAS catalogue, 31 SNPs were found to be associated with several diseases ( P <. - Full list of author information is available at the end of the article Hu et al. - For example, Joseph Pickrell and colleagues [8] performed genome-wide association studies (GWAS) of 42 traits or diseases to compare the genetic variants associated with multiple phenotypes and identified 341 loci associated with multiple traits. - Heid IM et al [9] per- formed a GWAS of fasting insulin, high-density lipopro- tein cholesterol (HDL-C) and triglyceride (TG) levels to identify 53 loci associated with a limited capacity to store fat in a healthy way, and this multi-trait approach could increase the power to gain insights into an other- wise difficult-to-grasp phenotype. - Goh et al [11] found that essen- tial human genes tended to encode hub proteins and were widely expressed in multiple tissues. - Many shared genetic variants are identified in linkage disequilibrium with variants associated with other human traits or dis- eases, and these pleiotropic connections connect the hu- man traits together [8, 12]. - In a previous study, we reported that biochemical indices are closely associated with disease. - Additionally, a genome-wide assay indicated that genes or loci associated with lipid traits are related to bio- chemical indices. - Although the role of genetic factors and gene polymorphisms in biochemical indices has been re- ported, the network of biochemical indices themselves, biochemical indices and genetic types are still puzzling.. - With the rapid advances in bioinformatics techniques, clarifying the biochemical indices network with genetic types becomes feasible.. - The aim of this study was to identify the shared gen- etics responsible for 29 biochemical indices in the FAMHES cohort using a phenomics approach. - Genetic and trait-based characteristics of 1999 samples A total of 1999 subjects with 29 biochemical indices that passed the QC call rate of 95% were analysed, and a total of 709,211 SNPs in these subjects were subjected to the subse- quent genetic analysis. - The average GWAS inflation factor for all 29 biochemical indices was 1.029 (range: 0.975–. - In addition, cluster analysis with the hclust package in the R package classified these 29 bio- chemical indices into 2 groups, with one group including blood urea nitrogen (BUN), cholesterol, glucose, testoster- one (TE), follicle-stimulating hormone (FSH), insulin, im- munoglobulin G (IgG), homocysteine (HCY), folate (FOL), alpha-fetoprotein (AFP), immunoglobulin A (IgA), low- density lipoprotein cholesterol (LDL-C), immunoglobulin M (IgM), C3, how-density lipoprotein cholesterol (HDL), TGs, and C-reactive protein (CRP). - In total, 208 correlated pairs among biochemical indices were found. - 1 The heatmaps based on the Pearson correlation for 29 biochemical indices in the FAMHES cohort. - Hu et al. - Six traits (IgA, IgG, HCY, AFP, IgE and B12) were the first top factors in the network of these 29 traits and were related to more than 20 traits.. - After integrating all 5313 genes and removing the free notes in the total network among 29 biochemical. - In these 71 genes, 38 genes were found to connect more than 5 other genes in the interactional network annotated from the BioGRID database [19] (Additional file 7: Table S3), which showed that essential genes related to multiple traits were lo- cated in the central gene interactional network.. - 1✕10 − 3 ) were associated with three or more clin- ical biochemical quantitative traits, and 13 of these 481 SNPs were related to more than 5 traits. - SNPs were related to three or more biochemical indices (Fig. - 2 Molecular comorbidity index (MCI) for 29 biochemical indices in the FAMHES cohort. - After integrating the SNPs associated with more than 2 traits(P <. - Among those SNPs, five SNPs (rs579459, rs649129, rs507666, rs495828, and rs651007) in ABO were associated with more than 10 quantitative traits and diseases. - One SNP (rs671) in ALDH2 was related to 21 traits, six SNPs (rs10519302, rs16964211, rs2305707, rs2414095, rs6493487 and rs727479) in or near CYP19A1 were mainly associated with hormone measure- ments. - Rs671 is a nonsynonymous (ns) SNP (G504 L) in the ALDH2 gene, which is located on chromosome 12. - We next investigated the impact of the ALDH2 G504 L muta- tion on the osteogenic and adipogenic differentiation of 3 T3-L1 preadipocytes. - 3 Correlation analysis based on linkage disequilibrium score regression (LDSC) for 29 biochemical indices in the FAMHES cohort. - 4 Circos plot of shared SNPs related to more than 3 biochemical indices based on analysis of individuals in the FAMHES cohort. - 10 − 4 ) associated with more than four biochemical indices are marked on the outside of the Circos plot. - In 2018, Ches- more used the same method and database and found that 44% of genes or gene regions were associated with two or more diseases or traits, a nearly two-fold in- crease to that of Sivakumaran S [27]. - Gene co-expression networks and novel mutations associated with many phenotypic traits were identified in maize [29, 30]. - Immunoglobulin is produced by plasma cells and lym- phocytes and is characteristic of these types of cells and plays an essential role in the body’s immune system. - In this study, we found that IgG, IgA, IgE and IgM were the central traits in the biochemical indices network, and these traits could be linked to 19 or more traits.. - HCY, a naturally occurring amino acid found in blood plasma, plays a central role in biochemical indices by. - High levels of HCY have been associated with several body dysfunctions, such as vascu- lature [32] and endothelial injury [33]. - Interestingly, vita- min B12 was identified as having a central role in the biochemical indices network by correlating to 21 other traits. - The polymorphisms in this gene are associated with myo- cardial infarction [41] and metabolic syndrome [42].. - Mutations of this gene participate in complement activation and inflamma- tion in the central nervous system, which leads to Par- kinson’s disease [44]. - These three genes may be hub genes in biochemical indices networks.. - 10–4) were associated with three or more traits and correlated with each other. - This phenomenon may provide important “scaffolding” to support a frame- work to explore the basic mechanism of biochemical indices.. - We found that 31 SNPs in 18 genes were associated with several traits and diseases. - five SNPs (rs579459, rs649129, rs507666, rs495828 and rs651007) of ABO were associated with cholesterol and LDL levels. - Six SNPs (rs10519302, rs16964211, rs2305707, rs2414095, rs6493487, rs727479) of CYP19A1 were associated with oestradiol levels.. - Rs671 in ALDH2 was associated with glucose, OSTEOC, and SHBG levels. - The rs671 mutation was found to be associated with several traits (BMI, osteocalcin, renal function-related traits [55], response to alcohol consumption [56, 57], triglyceride [17], haematological and biochemical traits [58], intracranial aneurysm [59],. - Using ALDH2 as an example to preliminarily explore its biological func- tion, the in vitro function testing of rs671 played a role in the proliferation and osteogenic and adipogenic differ- entiation of 3 T3-L1 preadipocytes.. - Kos- tem performed a follow-up analysis of SNPs associated with disease by setting a lower cut-off value and then analysed the particular values of the tag SNP statistic, pairwise correlation, and the effect size of the candidate SNP [63].. - Of these, IgA, IgG, HCY, AFP, IgE and B12 were the first top factors in the network.. - Our research is an experimental attempt to assess the network of shared genetics and 29 biochemical indices.. - We investigated the correlations among 29 biochemical indices through three biological information methods.. - First, we found that IgA, IgG, IgE, IgM, HCY, AFP and B12 were in the central community of 29 biochemical indices. - 10 − 4 ) were associated with more than 3 traits. - Thirty-one SNPs were associated with several. - We clarified that 29 biochemical indices were from a network and that hub variations/genes played a vital role in biological processes. - These findings highlight a network of shared genetics and 29 biochemical indices.. - Measurements of 29 biochemical indices. - call rate of 95% and were included in the final data ana- lysis. - The inferred genotypes of SNPs in the genome that were not directly genotyped were computed by the IMPUTE program [64] (e.g., SNPs catalogued in HapMap Phase II CHB population release #24). - proteins trait 1 → trait 2 are those proteins related to trait 1 that interact with the proteins associated with trait 2 (and vice versa protein- s trait 2 → trait 1. - between the LD and the associated signal can also be used to test the relationship between the two traits for all SNPs in the genome. - To further elucidate the correlations of these 29 biochemical indices in FAMHES from the genetic architecture, we applied LDSC to estimate the correlation of these 29 traits.. - The correlations among the 29 biochemical indices were computed by the CORR procedure using SAS 9.0 and defined as the Pearson correlation coefficient between the rank variables. - The datasets generated and analysed during the current study are available in the Genome variation Map (GVM) of National Genomics Data Center (NGDC) (Accession Number: GVM000052).. - The cluster dendrogram for the 29 biochemical indices from the FAMHES cohort created with the hclust win R package. - Network characteristics of 5313 associated genes for 29 biochemical indices in individuals from the FAMHES cohort were analysed by Cytoscape. - related to more than 3 traits were annotated in the HaploReg database.. - SNPs was associated with more than 1 trait.. - The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.. - Cai T, Zhang Y, Ho YL, Link N, Sun J, Huang J, Cai TA, Damrauer S, Ahuja Y, Honerlaw J, et al. - Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. - Liang Y, Tan A, Liang D, Yang X, Liao M, Gao Y, Jiang Y, Yao Z, Lin X, Lu Z, et al. - Chen D, Zhang H, Gao Y, Lu Z, Yao Z, Jiang Y, Lin X, Wu C, Yang X, Tan A, et al. - Tan A, Sun J, Xia N, Qin X, Hu Y, Zhang S, Tao S, Gao Y, Yang X, Zhang H, et al.. - Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Loh PR, ReproGen C, Psychiatric Genomics C, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control C, Duncan L, et al. - Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L, et al. - Role of homocysteine in the development of cardiovascular disease. - SNPs in BRAP associated with risk of myocardial infarction in Asian populations. - A phenomics-based strategy identifies loci on APOC1, BRAP, and PLCG1 associated with metabolic syndrome phenotype domains. - Brainstorm C, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, et al. - Association study of polymorphisms in the ABO gene with ischemic stroke in the Chinese population. - Zhang H, Zhang Z, Zhang J, Xu L, Ye Z, Hao Y, Cai B, Zhou S, Liu K, Sun L, et al. - Fine-mapping of ABO gene identifies two novel SNPs associated with large artery atherosclerotic stroke in a Chinese Han population. - Wang H, Li Q, Wang T, Yang G, Wang Y, Zhang X, Sang Q, Wang H, Zhao X, Xing Q, et al. - A common polymorphism in the human aromatase gene alters the risk for polycystic ovary syndrome and modifies aromatase activity in vitro. - Identification of a CYP19 gene single-nucleotide polymorphism associated with a reduced risk of coronary heart disease. - Okada Y, Sim X, Go MJ, Wu JY, Gu D, Takeuchi F, Takahashi A, Maeda S, Tsunoda T, Chen P, et al. - Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. - Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA. - Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk
Xem thử không khả dụng, vui lòng xem tại trang nguồn hoặc xem
Tóm tắt