- Heritability and genome-wide association analyses of fasting plasma glucose in. - Background: Currently, diabetes has become one of the leading causes of death worldwide. - Here we intend to study the magnitude of the genetic influence on FPG variation by conducting structural equation modelling analysis and to further identify specific genetic variants potentially related to FPG levels by performing a genome-wide association study (GWAS) in Chinese twins.. - The DZ twin correlation for the FPG level (r DZ CI was much lower than half that of the MZ twin correlation (r MZ CI . - In the GWAS, although no genetic variants reached the genome-wide significance level ( P <. - The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. - If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. - Full list of author information is available at the end of the article. - Conclusions: The FPG level is highly heritable in the Chinese population, and genetic variants are significantly involved in regulatory domains, functional genes and biological pathways that mediate FPG levels. - Keywords: Fasting plasma glucose, Heritability, Genome-wide association study, Twins, Chinese. - This condition is one of the leading causes of death worldwide, and higher fasting plasma glucose (FPG) levels, even if below the diagnostic thresh- old of diabetes, can also lead to increased morbidity and mortality. - And the heritability of the FPG level varied, with 0–0.77 in Europeans in Americans [9–. - However, few studies have explored the genetic effects on FPG levels in the Chinese population.. - Chinese population are different from other ethnic populations in the aspect of genetic constitutions. - Here, we performed this twin-based genetic epidemiological study to evaluate the magnitude of the genetic influence on FPG variation and further conducted a GWAS to identify specific genetic variants related to the FPG level in a sample of 382 Chinese twin pairs.. - 0.04–0.36) was much lower than half of the MZ twin correlation (r MZ CI suggesting the genetic effect on the FPG level (Additional file 2).. - The slight deviation in the upper right tail from the null distribution indicated evidence of a weak association. - None of the SNPs reached the genome-wide significance level (P <. - As shown in the regional association plot (Fig. - 0.05) in the subsequent gene-based analysis.. - reached the genome-wide significance level (P <. - with the FPG level (Additional file 3).. - Although none of the genes reached the genome-wide significance level (P <. - 1 Quantile-quantile (Q-Q) plot for genome-wide association study (GWAS) of the fasting plasma glucose level. - The x-axis shows the -log 10 of expected P -values of the association from the chi-square distribution, and the y-axis shows the -log 10 of P -values from the observed chi-square distribution. - Even no SNPs reached the genome-wide significance level, 28 SNPs showed suggestive evidence of an associ- ation with the FPG level. - In addition, SPATS2L was the topmost gene in the gene-based analysis. - In the gene-based analysis, 1007 genes were nominally associated with FPG levels. - 2 Manhattan plot for genome-wide association study (GWAS) of fasting plasma glucose level. - functions in glucose metabolism, and they may be po- tential candidate genes that need to be researched and validated in the future.. - SLC26A11 was involved in the transport of glu- cose and other sugars, bile salts and organic acids, metal ions and amine compounds, as indicated by the Gene- Cards database, while the mechanism of C1orf74 involved in blood glucose metabolism still needs to be explored.. - (4) in the presence of sufficient PDGF recep- tor, PDGF can activate protein kinase B and result in the transportation of glucose transporter 4 (GLUT 4) to the sur- face of the cell, which finally promotes the absorption of glu- cose and produces an insulin-like effect [53–55]. - for association with the FPG level in genome-wide association study SNP Chr band CHR BP P -value Closest genes or genes Official full name. - 3 Regional association plot showing signals around chromosomal loci (2q33.1) for genome-wide association study of the fasting plasma glucose level. - Represented the genes had already been indicated in the SNP-based analysis. - This study was with a relatively small sample size because of the difficulties of recruiting and identifying qualified twin pairs. - The FPG level is highly heritable in the Chinese population, and some genetic variants are involved in regulatory domains, functional genes and biological pathways that mediate FPG levels.. - REACTOME_PYRIMIDINE_METABOLISM 1.26E-03 1.03E . - REACTOME_PYRIMIDINE_CATABOLISM 1.26E-03 1.17E . - KEGG_PANTOTHENATE_AND_COA_BIOSYNTHESIS 1.26E-03 1.42E . - KEGG_BETA_ALANINE_METABOLISM 1.26E-03 1.37E . - REACTOME_REGULATION_OF_INSULIN_SECRETION_BY_GLUCAGON_LIKE_PEPTIDE1 1.42E-03 1.73E . - REACTOME_REGULATION_OF_INSULIN_SECRETION 1.64E-03 2.55E . - BIOCARTA_P38MAPK_PATHWAY 1.83E-03 4.87E . - REACTOME_GLUCAGON_SIGNALING_IN_METABOLIC_REGULATION 1.99E-03 2.10E . - BIOCARTA_IL1R_PATHWAY 2.06E-03 5.20E . - REACTOME_G1_S_SPECIFIC_TRANSCRIPTION 2.11E-03 2.31E . - BIOCARTA_SKP2E2F_PATHWAY 2.11E-03 1.94E . - BIOCARTA_RACCYCD_PATHWAY 2.11E-03 1.90E . - BIOCARTA_MCM_PATHWAY 2.11E-03 2.04E . - KEGG_PYRIMIDINE_METABOLISM 2.12E-03 1.51E . - REACTOME_SIGNALING_BY_PDGF 2.49E-03 2.37E . - KEGG_TASTE_TRANSDUCTION 2.64E-03 3.83E . - REACTOME_SYNTHESIS_OF_PIPS_AT_THE_PLASMA_MEMBRANE 2.69E-03 3.02E . - BIOCARTA_FMLP_PATHWAY 2.69E-03 2.60E . - BIOCARTA_NKT_PATHWAY 2.73E-03 9.20E . - BIOCARTA_TOB1_PATHWAY 2.82E-03 2.87E . - BIOCARTA_TGFB_PATHWAY 2.82E-03 3.01E . - BIOCARTA_ALK_PATHWAY 2.82E-03 3.05E . - KEGG_CYSTEINE_AND_METHIONINE_METABOLISM 2.85E-03 2.82E . - REACTOME_E2F_MEDIATED_REGULATION_OF_DNA_REPLICATION 3.05E-03 1.78E . - REACTOME_RORA_ACTIVATES_CIRCADIAN_EXPRESSION 3.06E-03 2.88E . - REACTOME_CIRCADIAN_REPRESSION_OF_EXPRESSION_BY_REV_ERBA 3.06E-03 2.82E . - BIOCARTA_RELA_PATHWAY 3.06E-03 2.99E . - BIOCARTA_RARRXR_PATHWAY 3.06E-03 3.06E . - Finally, a total of 382 twin pairs (139 DZ pairs and 243 MZ pairs) aged 18 years or older were included in the heritability analysis and the subset of 139 DZ twin pairs was further included in the GWAS. - In the classical twin design, the phenotypic variation was decomposed into that due to additive genetic (A), dominant genetic (D), and unique environmental or residual (E) influ- ences. - We performed a likelihood ratio test to compare the performances of the full ADE model and its nested model, i.e., AE model. - was set as genome-wide statistical significance.. - Bio- Carta, KEGG and Reactome were selected in the MSigDB database to obtain pathways and corresponding gene annotation [74].. - Then, the ex- pression levels of 25 genes, i.e., the genes where the top SNPs were located and the top 20 genes in the VEGAS2 analysis, between the two independent groups were compared by the Wilcoxon rank sum test. - Summary of the imputed SNPs with a P -value <. - 1 × 10 −5 for association of the FPG level in GWAS.. - GWAS: Genome-wide association study. - We thank Gu Zhu for providing technical guidance in the data analysis.. - All authors have read and approved this version of the article to be published.. - All authors agreed to be responsible for all aspects of the work.. - The dataset supporting the conclusions of this article is available in the European Variation Archive (EVA) repository (Accession No. - All participants provided written informed consent for participating in the study. - We have acquired administrative permission to access the data which was used in the research.. - Heritability estimates for beta cell function and features of the insulin resistance syndrome in UK families with an increased susceptibility to type 2 diabetes. - Heritabilities of the metabolic syndrome and its components in the northern Manhattan family study. - Genetic and environmental dissections of sub-phenotypes of metabolic syndrome in the Chinese population: a twin-based heritability study. - Heritabilities of the metabolic syndrome phenotypes and related factors in Korean twins. - Heritability of the metabolic syndrome and its components in the Tehran lipid and glucose study (TLGS).. - Heritability of determinants of the metabolic syndrome among healthy Arabs of the Oman family study. - 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