{"title":"特发性肺纤维化与1型糖尿病相关：一项双样本孟德尔随机研究","authors":"Leyan Chen, Tianzhichao Hou, Feifan Ge, Huachi Jiang, Feng Liu, Jingyan Tian, Mingfeng Zheng","doi":"10.1002/jgm.70008","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear; previous studies revealed the underlying connection between IPF and diabetes, but there is no consensual opinion. This study is aimed at examining the association between Type 1 diabetes (T1D) and IPF using Mendelian randomization (MR).</p>\n </section>\n \n <section>\n \n <h3> Method</h3>\n \n <p>In our two-sample MR study, we selected single nucleotide polymorphisms (SNPs) that are strongly associated with T1D in a genome-wide association study (GWAS) from IEU (dataset: ebi-a-GCST005536) and obtained their corresponding effect estimates on T1D risk in an IPF GWAS from IEU (dataset: finn-b-IPF). We conducted a multivariable Mendelian randomization (MVMR) analysis to eliminate the interference of aging.</p>\n </section>\n \n <section>\n \n <h3> Result</h3>\n \n <p>In the outcome of inverse-variance weighted (IVW) method, T1D showed a promoting effect on IPF (odds ratio (OR): 1.132, <i>p</i> = 0.005). The statistics passed the MR-PRESSO test, and no outliers were observed (global test <i>p</i> = 0.238). MVMR study was performed, and the aging-adjusted result remains almost the same (OR = 1.132, OR_95% CI: 1.034–1.239, <i>p</i> = 0.007).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our study shows a causal relation between T1D and IPF; further investigation should be conducted.</p>\n </section>\n </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 1","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Idiopathic Pulmonary Fibrosis Is Associated With Type 1 Diabetes: A Two-Sample Mendelian Randomization Study\",\"authors\":\"Leyan Chen, Tianzhichao Hou, Feifan Ge, Huachi Jiang, Feng Liu, Jingyan Tian, Mingfeng Zheng\",\"doi\":\"10.1002/jgm.70008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear; previous studies revealed the underlying connection between IPF and diabetes, but there is no consensual opinion. This study is aimed at examining the association between Type 1 diabetes (T1D) and IPF using Mendelian randomization (MR).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Method</h3>\\n \\n <p>In our two-sample MR study, we selected single nucleotide polymorphisms (SNPs) that are strongly associated with T1D in a genome-wide association study (GWAS) from IEU (dataset: ebi-a-GCST005536) and obtained their corresponding effect estimates on T1D risk in an IPF GWAS from IEU (dataset: finn-b-IPF). We conducted a multivariable Mendelian randomization (MVMR) analysis to eliminate the interference of aging.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Result</h3>\\n \\n <p>In the outcome of inverse-variance weighted (IVW) method, T1D showed a promoting effect on IPF (odds ratio (OR): 1.132, <i>p</i> = 0.005). The statistics passed the MR-PRESSO test, and no outliers were observed (global test <i>p</i> = 0.238). MVMR study was performed, and the aging-adjusted result remains almost the same (OR = 1.132, OR_95% CI: 1.034–1.239, <i>p</i> = 0.007).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our study shows a causal relation between T1D and IPF; further investigation should be conducted.</p>\\n </section>\\n </div>\",\"PeriodicalId\":56122,\"journal\":{\"name\":\"Journal of Gene Medicine\",\"volume\":\"27 1\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gene Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jgm.70008\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gene Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jgm.70008","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：特发性肺纤维化（IPF）的发病机制尚不清楚；先前的研究揭示了IPF和糖尿病之间的潜在联系，但没有共识。本研究旨在利用孟德尔随机化（MR）研究1型糖尿病（T1D）和IPF之间的关系。方法：在我们的两样本MR研究中，我们从IEU（数据集：ebi-a-GCST005536）的全基因组关联研究（GWAS）中选择了与T1D密切相关的单核苷酸多态性（snp），并从IEU（数据集：fin -b-IPF）中获得了它们对IPF GWAS中T1D风险的相应影响估计。我们进行了多变量孟德尔随机化（MVMR）分析，以消除衰老的干扰。结果：在反方差加权（IVW）法的结果中，T1D对IPF有促进作用（优势比（OR）： 1.132, p = 0.005）。统计量通过MR-PRESSO检验，未观察到异常值（全局检验p = 0.238）。进行MVMR研究，经年龄调整后的结果基本相同（OR = 1.132, OR_95% CI: 1.034-1.239, p = 0.007）。结论：我们的研究表明T1D与IPF之间存在因果关系；应进行进一步调查。
Idiopathic Pulmonary Fibrosis Is Associated With Type 1 Diabetes: A Two-Sample Mendelian Randomization Study
Background
The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear; previous studies revealed the underlying connection between IPF and diabetes, but there is no consensual opinion. This study is aimed at examining the association between Type 1 diabetes (T1D) and IPF using Mendelian randomization (MR).
Method
In our two-sample MR study, we selected single nucleotide polymorphisms (SNPs) that are strongly associated with T1D in a genome-wide association study (GWAS) from IEU (dataset: ebi-a-GCST005536) and obtained their corresponding effect estimates on T1D risk in an IPF GWAS from IEU (dataset: finn-b-IPF). We conducted a multivariable Mendelian randomization (MVMR) analysis to eliminate the interference of aging.
Result
In the outcome of inverse-variance weighted (IVW) method, T1D showed a promoting effect on IPF (odds ratio (OR): 1.132, p = 0.005). The statistics passed the MR-PRESSO test, and no outliers were observed (global test p = 0.238). MVMR study was performed, and the aging-adjusted result remains almost the same (OR = 1.132, OR_95% CI: 1.034–1.239, p = 0.007).
Conclusion
Our study shows a causal relation between T1D and IPF; further investigation should be conducted.
期刊介绍：
The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies.
Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials.
Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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