• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

包括外显子芯片标记物和 2 型糖尿病代谢物特征的遗传变异。

Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes.

机构信息

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

German Center for Diabetes Research (DZD), Neuherberg, Germany.

出版信息

Sci Rep. 2017 Jul 20;7(1):6037. doi: 10.1038/s41598-017-06158-3.

DOI:10.1038/s41598-017-06158-3
PMID:28729637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5519666/
Abstract

Diabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5). Gene-based tests on all exome chip variants revealed associations between GFRAL and PC aa C42:1/PC aa C42:0, BIN1 and SM (OH) C22:2/SM C18:0 and TFRC and SM (OH) C22:2/SM C16:1). Selecting variants for gene-based tests based on functional annotation identified one additional association between OR51Q1 and hexoses. Among single genetic variants consistently associated with diabetes-related metabolites, two (rs174550 (FADS1), rs3204953 (REV3L)) were significantly associated with type 2 diabetes in large-scale meta-analysis for type 2 diabetes. In conclusion, we identified a novel metabolite locus in single variant analyses and four genes within gene-based tests and confirmed two previously known mGWAS loci which might be relevant for the risk of type 2 diabetes.

摘要

与糖尿病相关的代谢物可能有助于鉴定 2 型糖尿病的新风险变异。在德国 EPIC-Potsdam 研究的一个亚组样本（n=2500）中使用靶向代谢组学，我们测试了之前发表的 SNP 与糖尿病相关代谢物的关联，并使用包括德国 KORA F4 研究 2692 名个体在内的外显子芯片数据进行了额外的探索性分析，结果在该研究中得到了复制。我们总共鉴定出了 16 个与糖尿病相关代谢物特征相关的基因座，包括 rs499974（MOGAT2）与二酰基磷脂酰胆碱比（PC aa C40:5/PC aa C38:5）之间的一个新关联。在外显子芯片所有变体的基因座测试中，发现 GFRAL 与 PC aa C42:1/PC aa C42:0、BIN1 和 SM（OH）C22:2/SM C18:0 以及 TFRC 和 SM（OH）C22:2/SM C16:1 之间存在关联。基于功能注释选择基因座测试变体时，鉴定出了 OR51Q1 与己糖之间的另一个关联。在与糖尿病相关代谢物一致相关的单遗传变体中，两个变体（rs174550（FADS1）、rs3204953（REV3L））在 2 型糖尿病的大规模荟萃分析中与 2 型糖尿病显著相关。总之，我们在单变体分析中鉴定出了一个新的代谢物基因座和基因座测试中的四个基因，并证实了两个先前已知的 mGWAS 基因座可能与 2 型糖尿病的风险相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c88d/5519666/060669de7412/41598_2017_6158_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c88d/5519666/e70330923274/41598_2017_6158_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c88d/5519666/060669de7412/41598_2017_6158_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c88d/5519666/e70330923274/41598_2017_6158_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c88d/5519666/060669de7412/41598_2017_6158_Fig2_HTML.jpg

相似文献

1
Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes.包括外显子芯片标记物和 2 型糖尿病代谢物特征的遗传变异。
Sci Rep. 2017 Jul 20;7(1):6037. doi: 10.1038/s41598-017-06158-3.
2
Identification of novel non-synonymous variants associated with type 2 diabetes-related metabolites in Korean population.鉴定与韩国人群 2 型糖尿病相关代谢物相关的新型非同义变异。
Biosci Rep. 2019 Oct 30;39(10). doi: 10.1042/BSR20190078.
3
A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos.一项全基因组关联研究在西班牙裔社区健康研究/拉丁裔研究中发现了人类代谢组的 46 个位点。
Am J Hum Genet. 2020 Nov 5;107(5):849-863. doi: 10.1016/j.ajhg.2020.09.003. Epub 2020 Oct 7.
4
Associations of anthropometric markers with serum metabolites using a targeted metabolomics approach: results of the EPIC-potsdam study.采用靶向代谢组学方法研究人体测量学标志物与血清代谢物的相关性：EPIC-波茨坦研究的结果。
Nutr Diabetes. 2016 Jun 27;6(6):e215. doi: 10.1038/nutd.2016.23.
5
Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.外显子芯片关联分析揭示了PAX4基因中一个亚洲特异性错义变异，该变异与中国人群的2型糖尿病相关。
Diabetologia. 2017 Jan;60(1):107-115. doi: 10.1007/s00125-016-4132-z. Epub 2016 Oct 15.
6
Insight in genome-wide association of metabolite quantitative traits by exome sequence analyses.通过外显子序列分析洞察代谢物数量性状的全基因组关联
PLoS Genet. 2015 Jan 8;11(1):e1004835. doi: 10.1371/journal.pgen.1004835. eCollection 2015 Jan.
7
Exome arrays capture polygenic rare variant contributions to schizophrenia.外显子组芯片捕获了多基因罕见变异对精神分裂症的影响。
Hum Mol Genet. 2016 Mar 1;25(5):1001-7. doi: 10.1093/hmg/ddv620. Epub 2016 Jan 5.
8
Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes.非靶向代谢组学与基因分析相结合，确定胆汁酸合成和磷脂代谢与2型糖尿病的发生有关。
Diabetologia. 2016 Oct;59(10):2114-24. doi: 10.1007/s00125-016-4041-1. Epub 2016 Jul 12.
9
Lack of significant effects of the type 2 diabetes susceptibility loci JAZF1, CDC123/CAMK1D, NOTCH2, ADAMTS9, THADA, and TSPAN8/LGR5 on diabetes and quantitative metabolic traits.2 型糖尿病易感基因 JAZF1、CDC123/CAMK1D、NOTCH2、ADAMTS9、THADA 和 TSPAN8/LGR5 对糖尿病及定量代谢特征无显著影响。
Horm Metab Res. 2010 Jan;42(1):14-22. doi: 10.1055/s-0029-1233480. Epub 2009 Aug 10.
10
An exome array study of the plasma metabolome.血浆代谢组的外显子组研究。
Nat Commun. 2016 Jul 25;7:12360. doi: 10.1038/ncomms12360.

引用本文的文献

1
Humanized monoacylglycerol acyltransferase 2 mice develop metabolic dysfunction-associated steatohepatitis.人源化单酰甘油酰基转移酶2小鼠会发展出代谢功能障碍相关的脂肪性肝炎。
J Lipid Res. 2024 Dec;65(12):100695. doi: 10.1016/j.jlr.2024.100695. Epub 2024 Nov 5.
2
A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma.一种新型代谢相关特征作为肝细胞癌潜在预后生物标志物
J Hepatocell Carcinoma. 2021 Mar 16;8:119-132. doi: 10.2147/JHC.S294108. eCollection 2021.
3
A network analysis framework of genetic and nongenetic risks for type 2 diabetes.

本文引用的文献

1
PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c.PATZ1通过与rs174557结合下调FADS1，并受到SP1/SREBP1c的拮抗。
Nucleic Acids Res. 2017 Mar 17;45(5):2408-2422. doi: 10.1093/nar/gkw1186.
2
Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes.非靶向代谢组学与基因分析相结合，确定胆汁酸合成和磷脂代谢与2型糖尿病的发生有关。
Diabetologia. 2016 Oct;59(10):2114-24. doi: 10.1007/s00125-016-4041-1. Epub 2016 Jul 12.
3
PhenoScanner: a database of human genotype-phenotype associations.
2 型糖尿病遗传和非遗传风险的网络分析框架。
Rev Endocr Metab Disord. 2021 Jun;22(2):461-469. doi: 10.1007/s11154-020-09585-2. Epub 2020 Sep 14.
4
The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders.环状 RNA 在肥胖症及相关代谢紊乱中的新兴作用和前景。
Cells. 2020 Jun 16;9(6):1473. doi: 10.3390/cells9061473.
5
Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR.通过生物信息学分析鉴定影响结直肠癌转移的新型生物标志物，并通过qRT-PCR进行验证。
Cancer Cell Int. 2020 Mar 30;20:105. doi: 10.1186/s12935-020-01180-4. eCollection 2020.
6
Identification of novel non-synonymous variants associated with type 2 diabetes-related metabolites in Korean population.鉴定与韩国人群 2 型糖尿病相关代谢物相关的新型非同义变异。
Biosci Rep. 2019 Oct 30;39(10). doi: 10.1042/BSR20190078.
7
Relationships of Non-coding RNA with diabetes and depression.非编码 RNA 与糖尿病和抑郁症的关系。
Sci Rep. 2019 Jul 24;9(1):10707. doi: 10.1038/s41598-019-47077-9.
8
Identification of novel alleles associated with insulin resistance in childhood obesity using pooled-DNA genome-wide association study approach.采用 Pooled-DNA 全基因组关联研究方法鉴定与儿童肥胖相关的胰岛素抵抗新等位基因。
Int J Obes (Lond). 2018 Apr;42(4):686-695. doi: 10.1038/ijo.2017.293. Epub 2017 Nov 30.
PhenoScanner：一个人类基因型-表型关联数据库。
Bioinformatics. 2016 Oct 15;32(20):3207-3209. doi: 10.1093/bioinformatics/btw373. Epub 2016 Jun 17.
4
Genetic Influences on Metabolite Levels: A Comparison across Metabolomic Platforms.代谢物水平的遗传影响：跨代谢组学平台的比较
PLoS One. 2016 Apr 13;11(4):e0153672. doi: 10.1371/journal.pone.0153672. eCollection 2016.
5
Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.全基因组循环代谢物研究鉴定出62个基因座并揭示溶血磷脂酸的新系统效应。
Nat Commun. 2016 Mar 23;7:11122. doi: 10.1038/ncomms11122.
6
Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.人类REV3 DNA聚合酶ζ定位于线粒体并保护线粒体基因组。
PLoS One. 2015 Oct 13;10(10):e0140409. doi: 10.1371/journal.pone.0140409. eCollection 2015.
7
Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.大规模基因组分析将生殖衰老与下丘脑信号传导、乳腺癌易感性及BRCA1介导的DNA修复联系起来。
Nat Genet. 2015 Nov;47(11):1294-1303. doi: 10.1038/ng.3412. Epub 2015 Sep 28.
8
Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels.全基因组关联研究确定了导致血液代谢物水平变异的新型遗传变异。
Nat Commun. 2015 Jun 12;6:7208. doi: 10.1038/ncomms8208.
9
Evidence for DNA damage as a biological link between diabetes and cancer.DNA损伤作为糖尿病与癌症之间生物学联系的证据。
Chin Med J (Engl). 2015 Jun 5;128(11):1543-8. doi: 10.4103/0366-6999.157693.
10
Mendelian randomization studies: a review of the approaches used and the quality of reporting.孟德尔随机化研究：方法学综述及报告质量评估。
Int J Epidemiol. 2015 Apr;44(2):496-511. doi: 10.1093/ije/dyv071. Epub 2015 May 6.