文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
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
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
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 @ 2025

在一项多血统荟萃分析中，对 140 万参与者进行研究，发现了 318 个 2 型糖尿病和相关血管结局的新风险位点。

Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.

机构信息

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.

Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

出版信息

Nat Genet. 2020 Jul;52(7):680-691. doi: 10.1038/s41588-020-0637-y. Epub 2020 Jun 15.

DOI:10.1038/s41588-020-0637-y
PMID:32541925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7343592/
Abstract

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.

摘要

我们通过百万退伍军人计划（MVP）、DIAMANTE、日本生物银行和其他研究中 228499 例病例和 1178783 例对照的多祖系荟萃分析研究了 2 型糖尿病（T2D）的遗传易感性。我们报告了 568 个关联，包括 286 个常染色体、7 个 X 染色体和 25 个在特定祖先分析中未报告的关联。全转录组关联分析在 687 个新基因中检测到 3568 个与 T2D 相关的基因表达的关联；其中 54 个已知与 FDA 批准的药物相互作用。多基因风险评分（PRS）与 T2D 相关的视网膜病变风险增加强烈相关，与慢性肾病（CKD）、外周动脉疾病（PAD）和神经病变中度相关。我们在 MVP 中研究了 T2D 相关血管结局的遗传病因，并在 13 个变体（包括冠心病（CHD）、CKD、PAD 和神经病变）中观察到 SNP-T2D 相互作用。这些发现可能有助于确定 T2D 的潜在治疗靶点以及将 T2D 与血管结局联系起来的基因组途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/3ee0c53cb038/nihms-1589535-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/874c53051149/nihms-1589535-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/7282957d464d/nihms-1589535-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/851a0cc3fe77/nihms-1589535-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/2eb13dd4e861/nihms-1589535-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/96b96371ee91/nihms-1589535-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/5f0f93b9cfc7/nihms-1589535-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/3ee0c53cb038/nihms-1589535-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/874c53051149/nihms-1589535-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/7282957d464d/nihms-1589535-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/851a0cc3fe77/nihms-1589535-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/2eb13dd4e861/nihms-1589535-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/96b96371ee91/nihms-1589535-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/5f0f93b9cfc7/nihms-1589535-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a62/7343592/3ee0c53cb038/nihms-1589535-f0002.jpg

相似文献

[1]
Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.

Nat Genet. 2020-6-15

[2]
Impact of the trans-ancestry polygenic risk score on type 2 diabetes risk, onset age and progression among population in Taiwan.

Am J Physiol Endocrinol Metab. 2024-5-1

[3]
Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.

Nat Genet. 2017-10

[4]
Ancestry effects on type 2 diabetes genetic risk inference in Hispanic/Latino populations.

BMC Med Genet. 2020-6-25

[5]
The ras responsive transcription factor RREB1 is a novel candidate gene for type 2 diabetes associated end-stage kidney disease.

Hum Mol Genet. 2014-12-15

[6]
Genes associated with Type 2 Diabetes and vascular complications.

Aging (Albany NY). 2018-2-4

[7]
Additional common variants associated with type 2 diabetes and coronary artery disease detected using a pleiotropic cFDR method.

J Diabetes Complications. 2018-9-9

[8]
What is the contribution of two genetic variants regulating VEGF levels to type 2 diabetes risk and to microvascular complications?

PLoS One. 2013-2-6

[9]
Evaluation of genome-wide association study-identified type 2 diabetes loci in African Americans.

Am J Epidemiol. 2012-11-9

[10]
Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Nature. 2024-3

引用本文的文献

[1]
Modeling Genetic Risk of β-Cell Dysfunction in Human Induced Pluripotent Stem Cells From Patients Carrying the MTNR1B Risk Variant.

J Pineal Res. 2025-9

[2]
Interaction between coffee consumption and polygenic risk score in relation to diabetes: insights from the Maastricht study.

Eur J Nutr. 2025-8-20

[3]
EAT-Lancet diet and risk of metabolic dysfunction-associated steatotic liver disease and other liver chronic diseases: a large prospective cohort study in the UK Biobank.

Front Nutr. 2025-7-31

[4]
Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study.

Commun Biol. 2025-8-15

[5]
European and African ancestry-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites.

Nat Commun. 2025-8-11

[6]
Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

medRxiv. 2025-7-23

[7]
Genetically proxied glucagon-like peptide-1 receptor perturbation and risk of mood disorders: a Mendelian randomization study.

BMC Psychiatry. 2025-8-6

[8]
The role of the beta cell in type 2 diabetes: new findings from the last 5 years.

Diabetologia. 2025-8-6

[9]
Multimodal AI correlates of glucose spikes in people with normal glucose regulation, pre-diabetes and type 2 diabetes.

Nat Med. 2025-7-31

[10]
Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI.

Front Genet. 2025-7-16

本文引用的文献

[1]
Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies.

Am J Hum Genet. 2019-9-26

[2]
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Nature. 2019-5-22

[3]
Genome-wide association study of type 2 diabetes in Africa.

Diabetologia. 2019-5-2

[4]
Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.

Nat Genet. 2019-2-4

[5]
Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization.

Circ Genom Precis Med. 2018-11

[6]
An atlas of genetic associations in UK Biobank.

Nat Genet. 2018-10-22

[7]
Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.

Nat Genet. 2018-10-8

[8]
Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

Nat Genet. 2018-10-1

[9]
Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.

Nat Commun. 2018-7-27

[10]
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

Nat Genet. 2018-4-9

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索