{"title":"遗传共病机制的新见解：2型糖尿病和原发性开角型青光眼。","authors":"Yixu Wang, Ye Tian, Yumeng Quan, Shuyan Zhou, Yufei Dang, Xiaoxia Zhang, Cheng Pei","doi":"10.1136/bmjophth-2025-002219","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>To investigate the shared genetic mechanisms between type 2 diabetes (T2D) and primary open-angle glaucoma (POAG). Using large-scale genome-wide association study (GWAS) data, we performed single nucleotide polymorphism (SNP) level analysis to detect pleiotropic variants and loci, paired eQTL mapping analysis and gene-level analysis to identify candidate pleiotropic genes. In addition, Mendelian randomisation (MR) analysis was performed to assess causal associations.</p><p><strong>Materials and methods: </strong>We used POAG GWAS data from Finngen (9565 cases and 430 250 controls) and T2D GWAS data from 55 555 European ancestry samples. We used Linkage Disequilibrium SCore (LDSC) regression to assess the genetic association between T2D and POAG and further used PLeiotropic Analysis under the COmposite null hypothesis (PLACO) to identify shared genetic variants between paired traits. Finally, we further used MR analysis to explore the causal association between T2D and POAG at the genetic level.</p><p><strong>Results: </strong>The LDSC results and MR analysis revealed that the T2D effect was significantly higher than that of the POAG (OR=1.09, 95% CI 1.03 to 1.14, p=1.50×10<sup>-3</sup>). The PLACO property analysis determined that the T2D sum POAG shared 178 individual SNPs, separate localisation of 79 individual causes. The five most popular choices are based on the effectiveness of <i>CCND2</i>, <i>SVEP1</i>, <i>ST6GAL1</i>, <i>TCF7L2</i> and <i>HMGA2</i>. expression quantitative trait loci mapping further revealed 36 genes with regulatory roles in optic nerve-related brain tissues. Functional enrichment analyses indicated that these pleiotropic genes are involved in neurodevelopmental, neuroprotective and metabolic pathways, with tissue-specific enrichment observed in neural, pancreatic, adipose and retinal tissues. It is possible to present the main comorbid mechanisms of T2D and POAG.</p><p><strong>Conclusions: </strong>Our study provides new insights into the aetiology and pathogenesis of T2D and POAG at the genetic level.</p>","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"10 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273101/pdf/","citationCount":"0","resultStr":"{\"title\":\"New insights into genetic comorbidity mechanisms: type 2 diabetes and primary open-angle glaucoma.\",\"authors\":\"Yixu Wang, Ye Tian, Yumeng Quan, Shuyan Zhou, Yufei Dang, Xiaoxia Zhang, Cheng Pei\",\"doi\":\"10.1136/bmjophth-2025-002219\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>To investigate the shared genetic mechanisms between type 2 diabetes (T2D) and primary open-angle glaucoma (POAG). Using large-scale genome-wide association study (GWAS) data, we performed single nucleotide polymorphism (SNP) level analysis to detect pleiotropic variants and loci, paired eQTL mapping analysis and gene-level analysis to identify candidate pleiotropic genes. In addition, Mendelian randomisation (MR) analysis was performed to assess causal associations.</p><p><strong>Materials and methods: </strong>We used POAG GWAS data from Finngen (9565 cases and 430 250 controls) and T2D GWAS data from 55 555 European ancestry samples. We used Linkage Disequilibrium SCore (LDSC) regression to assess the genetic association between T2D and POAG and further used PLeiotropic Analysis under the COmposite null hypothesis (PLACO) to identify shared genetic variants between paired traits. Finally, we further used MR analysis to explore the causal association between T2D and POAG at the genetic level.</p><p><strong>Results: </strong>The LDSC results and MR analysis revealed that the T2D effect was significantly higher than that of the POAG (OR=1.09, 95% CI 1.03 to 1.14, p=1.50×10<sup>-3</sup>). The PLACO property analysis determined that the T2D sum POAG shared 178 individual SNPs, separate localisation of 79 individual causes. The five most popular choices are based on the effectiveness of <i>CCND2</i>, <i>SVEP1</i>, <i>ST6GAL1</i>, <i>TCF7L2</i> and <i>HMGA2</i>. expression quantitative trait loci mapping further revealed 36 genes with regulatory roles in optic nerve-related brain tissues. Functional enrichment analyses indicated that these pleiotropic genes are involved in neurodevelopmental, neuroprotective and metabolic pathways, with tissue-specific enrichment observed in neural, pancreatic, adipose and retinal tissues. It is possible to present the main comorbid mechanisms of T2D and POAG.</p><p><strong>Conclusions: </strong>Our study provides new insights into the aetiology and pathogenesis of T2D and POAG at the genetic level.</p>\",\"PeriodicalId\":9286,\"journal\":{\"name\":\"BMJ Open Ophthalmology\",\"volume\":\"10 1\",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273101/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMJ Open Ophthalmology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1136/bmjophth-2025-002219\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Ophthalmology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1136/bmjophth-2025-002219","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
New insights into genetic comorbidity mechanisms: type 2 diabetes and primary open-angle glaucoma.
Aims: To investigate the shared genetic mechanisms between type 2 diabetes (T2D) and primary open-angle glaucoma (POAG). Using large-scale genome-wide association study (GWAS) data, we performed single nucleotide polymorphism (SNP) level analysis to detect pleiotropic variants and loci, paired eQTL mapping analysis and gene-level analysis to identify candidate pleiotropic genes. In addition, Mendelian randomisation (MR) analysis was performed to assess causal associations.
Materials and methods: We used POAG GWAS data from Finngen (9565 cases and 430 250 controls) and T2D GWAS data from 55 555 European ancestry samples. We used Linkage Disequilibrium SCore (LDSC) regression to assess the genetic association between T2D and POAG and further used PLeiotropic Analysis under the COmposite null hypothesis (PLACO) to identify shared genetic variants between paired traits. Finally, we further used MR analysis to explore the causal association between T2D and POAG at the genetic level.
Results: The LDSC results and MR analysis revealed that the T2D effect was significantly higher than that of the POAG (OR=1.09, 95% CI 1.03 to 1.14, p=1.50×10-3). The PLACO property analysis determined that the T2D sum POAG shared 178 individual SNPs, separate localisation of 79 individual causes. The five most popular choices are based on the effectiveness of CCND2, SVEP1, ST6GAL1, TCF7L2 and HMGA2. expression quantitative trait loci mapping further revealed 36 genes with regulatory roles in optic nerve-related brain tissues. Functional enrichment analyses indicated that these pleiotropic genes are involved in neurodevelopmental, neuroprotective and metabolic pathways, with tissue-specific enrichment observed in neural, pancreatic, adipose and retinal tissues. It is possible to present the main comorbid mechanisms of T2D and POAG.
Conclusions: Our study provides new insights into the aetiology and pathogenesis of T2D and POAG at the genetic level.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
