• 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

糖尿病风险基因座相关通路在代谢组织中是共享的。

Diabetes risk loci-associated pathways are shared across metabolic tissues.

机构信息

Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, the Netherlands.

Department of Epidemiology and Data Science, Amsterdam UMC, Location VUMC, Amsterdam Public Health Institute, Amsterdam, the Netherlands.

出版信息

BMC Genomics. 2022 May 14;23(1):368. doi: 10.1186/s12864-022-08587-5.

DOI:10.1186/s12864-022-08587-5
PMID:35568807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9107144/
Abstract

AIMS/HYPOTHESIS: Numerous genome-wide association studies have been performed to understand the influence of genetic variation on type 2 diabetes etiology. Many identified risk variants are located in non-coding and intergenic regions, which complicates understanding of how genes and their downstream pathways are influenced. An integrative data approach will help to understand the mechanism and consequences of identified risk variants.

METHODS

In the current study we use our previously developed method CONQUER to overlap 403 type 2 diabetes risk variants with regulatory, expression and protein data to identify tissue-shared disease-relevant mechanisms.

RESULTS

One SNP rs474513 was found to be an expression-, protein- and metabolite QTL. Rs474513 influenced LPA mRNA and protein levels in the pancreas and plasma, respectively. On the pathway level, in investigated tissues most SNPs linked to metabolism. However, in eleven of the twelve tissues investigated nine SNPs were linked to differential expression of the ribosome pathway. Furthermore, seven SNPs were linked to altered expression of genes linked to the immune system. Among them, rs601945 was found to influence multiple HLA genes, including HLA-DQA2, in all twelve tissues investigated.

CONCLUSION

Our results show that in addition to the classical metabolism pathways, other pathways may be important to type 2 diabetes that show a potential overlap with type 1 diabetes.

摘要

目的/假设：为了了解遗传变异对 2 型糖尿病病因的影响，已经进行了许多全基因组关联研究。许多已确定的风险变异位于非编码和基因间区域，这增加了理解基因及其下游途径如何受到影响的难度。综合数据方法将有助于理解已确定风险变异的机制和后果。

方法

在目前的研究中，我们使用我们之前开发的方法 CONQUER 将 403 个 2 型糖尿病风险变异与调节、表达和蛋白质数据重叠，以识别组织共享的疾病相关机制。

结果

发现一个 SNP rs474513 是一个表达、蛋白质和代谢物 QTL。rs474513 分别影响胰腺和血浆中的 LPA mRNA 和蛋白质水平。在途径水平上，在所研究的组织中，大多数与代谢相关的 SNP 都与代谢有关。然而，在所研究的 12 个组织中的 11 个中，9 个 SNP 与核糖体途径的差异表达有关。此外，有七个 SNP 与免疫系统相关基因的表达改变有关。其中，rs601945 被发现影响包括 HLA-DQA2 在内的多个 HLA 基因，在所有 12 个组织中都有影响。

结论

我们的结果表明，除了经典的代谢途径外，其他途径可能对 2 型糖尿病也很重要，这与 1 型糖尿病有潜在的重叠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/3c964a614687/12864_2022_8587_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/963ac52edc1c/12864_2022_8587_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/62551fa02d9e/12864_2022_8587_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/f86e4d422020/12864_2022_8587_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/3c964a614687/12864_2022_8587_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/963ac52edc1c/12864_2022_8587_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/62551fa02d9e/12864_2022_8587_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/f86e4d422020/12864_2022_8587_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/9107144/3c964a614687/12864_2022_8587_Fig4_HTML.jpg

相似文献

1
Diabetes risk loci-associated pathways are shared across metabolic tissues.糖尿病风险基因座相关通路在代谢组织中是共享的。
BMC Genomics. 2022 May 14;23(1):368. doi: 10.1186/s12864-022-08587-5.
2
Shared genetic etiology underlying Alzheimer's disease and type 2 diabetes.阿尔茨海默病和2型糖尿病潜在的共同遗传病因。
Mol Aspects Med. 2015 Jun-Oct;43-44:66-76. doi: 10.1016/j.mam.2015.06.006. Epub 2015 Jun 23.
3
Identification of novel variants associated with osteoporosis, type 2 diabetes and potentially pleiotropic loci using pleiotropic cFDR method.利用多效性 cFDR 方法鉴定与骨质疏松症、2 型糖尿病相关的新型变异体和潜在的多效性基因座。
Bone. 2018 Dec;117:6-14. doi: 10.1016/j.bone.2018.08.020. Epub 2018 Aug 30.
4
Functional relevance for type 1 diabetes mellitus-associated genetic variants by using integrative analyses.通过综合分析探讨1型糖尿病相关基因变异的功能相关性。
Hum Immunol. 2015 Oct;76(10):753-8. doi: 10.1016/j.humimm.2015.09.033. Epub 2015 Sep 30.
5
Increased identification of novel variants in type 2 diabetes, birth weight and their pleiotropic loci.鉴定 2 型糖尿病、出生体重及其多效性位点的新型变异。
J Diabetes. 2017 Oct;9(10):898-907. doi: 10.1111/1753-0407.12510. Epub 2017 Jan 20.
6
An Integrative Phenotype-Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies as a Candidate Gene for Obesity and Type 2 Diabetes.一种基于阿联酋国家糖尿病研究中表型特征的综合表型-基因型方法，将 鉴定为肥胖和 2 型糖尿病的候选基因。
Genes (Basel). 2020 Apr 23;11(4):461. doi: 10.3390/genes11040461.
7
Genetic predisposition in the 2'-5'A pathway in the development of type 1 diabetes: potential contribution to dysregulation of innate antiviral immunity.2'-5' 寡聚腺苷酸合成酶（2'-5'A）通路中的遗传易感性在 1 型糖尿病发病机制中的作用：对固有抗病毒免疫失调的潜在贡献。
Diabetologia. 2021 Aug;64(8):1805-1815. doi: 10.1007/s00125-021-05469-5. Epub 2021 May 11.
8
Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes.疾病特异性单核苷酸多态性、表达数量性状基因座和共表达网络的整合揭示了 2 型糖尿病的新候选基因。
Diabetologia. 2012 Aug;55(8):2205-13. doi: 10.1007/s00125-012-2568-3. Epub 2012 May 16.
9
Next steps in the identification of gene targets for type 1 diabetes.1 型糖尿病基因靶点鉴定的下一步。
Diabetologia. 2020 Nov;63(11):2260-2269. doi: 10.1007/s00125-020-05248-8. Epub 2020 Aug 14.
10
Circulating Adiponectin and Its Association with Metabolic Traits and Type 2 Diabetes: Gene-Diet Interactions Focusing on Selected Gene Variants and at the Genome-Wide Level in High-Cardiovascular Risk Mediterranean Subjects.循环脂联素及其与代谢特征和 2 型糖尿病的关系：重点关注特定基因变异和全基因组水平的高心血管风险地中海人群的基因-饮食相互作用。
Nutrients. 2021 Feb 7;13(2):541. doi: 10.3390/nu13020541.

引用本文的文献

1
gsQTL: Associating genetic risk variants with gene sets by exploiting their shared variability.基因集定量性状位点：通过利用遗传风险变异与基因集的共享变异性来关联二者。
bioRxiv. 2024 Sep 16:2024.09.13.612853. doi: 10.1101/2024.09.13.612853.

本文引用的文献

1
CONQUER: an interactive toolbox to understand functional consequences of GWAS hits.CONQUER：一个用于理解全基因组关联研究（GWAS）结果功能影响的交互式工具箱。
NAR Genom Bioinform. 2020 Oct 27;2(4):lqaa085. doi: 10.1093/nargab/lqaa085. eCollection 2020 Dec.
2
A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context.对代谢产物遗传学的综合研究揭示了跨时间和跨环境的强多效性和异质性。
Nat Commun. 2019 Oct 21;10(1):4788. doi: 10.1038/s41467-019-12703-7.
3
Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.
激光捕获微切割人类胰岛揭示了与 2 型糖尿病相关的新型 eQTLs。
Mol Metab. 2019 Jun;24:98-107. doi: 10.1016/j.molmet.2019.03.004. Epub 2019 Mar 18.
4
Developing a network view of type 2 diabetes risk pathways through integration of genetic, genomic and functional data.通过整合遗传、基因组和功能数据来构建 2 型糖尿病风险途径的网络视图。
Genome Med. 2019 Mar 26;11(1):19. doi: 10.1186/s13073-019-0628-8.
5
Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.在日本人群中鉴定出 28 个 2 型糖尿病的新易感位点。
Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
6
Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study.脂蛋白(a)水平与糖尿病或糖尿病前期个体心血管疾病事件的风险：社区动脉粥样硬化风险研究。
Atherosclerosis. 2019 Mar;282:52-56. doi: 10.1016/j.atherosclerosis.2018.12.022. Epub 2018 Dec 30.
7
Leveraging Polygenic Functional Enrichment to Improve GWAS Power.利用多基因功能富集提高 GWAS 效力。
Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
8
17B-hydroxysteroid dehydrogenases as acyl thioester metabolizing enzymes.17B-羟甾类脱氢酶作为酰基辅酶 A 硫酯代谢酶。
Mol Cell Endocrinol. 2019 Jun 1;489:107-118. doi: 10.1016/j.mce.2018.11.012. Epub 2018 Nov 30.
9
Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.利用高密度基因分型和胰岛特异性表观基因组图谱对 2 型糖尿病位点进行精细映射到单变体分辨率。
Nat Genet. 2018 Nov;50(11):1505-1513. doi: 10.1038/s41588-018-0241-6. Epub 2018 Oct 8.
10
Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease.全基因组血浆蛋白 QTL 图谱分析鉴定心血管疾病的潜在因果基因和途径。
Nat Commun. 2018 Aug 15;9(1):3268. doi: 10.1038/s41467-018-05512-x.