Delnaz Roshandel, Athina Spiliopoulou, Stuart J McGurnaghan, Andrii Iakovliev, Debby Lipschutz, Caroline Hayward, Shelley B Bull, Barbara E K Klein, Kristine E Lee, Gregory L Kinney, Marian Rewers, Tina Costacou, Rachel G Miller, Paul M McKeigue, Andrew D Paterson, Helen M Colhoun
{"title":"1 型糖尿病患者 C 肽的遗传与诊断年龄。","authors":"Delnaz Roshandel, Athina Spiliopoulou, Stuart J McGurnaghan, Andrii Iakovliev, Debby Lipschutz, Caroline Hayward, Shelley B Bull, Barbara E K Klein, Kristine E Lee, Gregory L Kinney, Marian Rewers, Tina Costacou, Rachel G Miller, Paul M McKeigue, Andrew D Paterson, Helen M Colhoun","doi":"10.2337/db24-0340","DOIUrl":null,"url":null,"abstract":"<p><strong>Article highlights: </strong>Identified genetic loci for C-peptide and type 1 diabetes (T1D) age at diagnosis (AAD) explain only a small proportion of their variation. We aimed to identify additional genetic loci associated with C-peptide and AAD. Some HLA allele/haplotypes associated with T1D also contributed to variability of C-peptide and AAD, whereas outside the HLA region, T1D loci were mostly not associated with C-peptide or AAD. Genetic variation within CTSH can affect AAD. There is still residual heritability of C-peptide and AAD outside of HLA that could benefit from larger meta-genome-wide association studies.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"223-233"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755686/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetics of C-Peptide and Age at Diagnosis in Type 1 Diabetes.\",\"authors\":\"Delnaz Roshandel, Athina Spiliopoulou, Stuart J McGurnaghan, Andrii Iakovliev, Debby Lipschutz, Caroline Hayward, Shelley B Bull, Barbara E K Klein, Kristine E Lee, Gregory L Kinney, Marian Rewers, Tina Costacou, Rachel G Miller, Paul M McKeigue, Andrew D Paterson, Helen M Colhoun\",\"doi\":\"10.2337/db24-0340\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Article highlights: </strong>Identified genetic loci for C-peptide and type 1 diabetes (T1D) age at diagnosis (AAD) explain only a small proportion of their variation. We aimed to identify additional genetic loci associated with C-peptide and AAD. Some HLA allele/haplotypes associated with T1D also contributed to variability of C-peptide and AAD, whereas outside the HLA region, T1D loci were mostly not associated with C-peptide or AAD. Genetic variation within CTSH can affect AAD. There is still residual heritability of C-peptide and AAD outside of HLA that could benefit from larger meta-genome-wide association studies.</p>\",\"PeriodicalId\":93977,\"journal\":{\"name\":\"Diabetes\",\"volume\":\" \",\"pages\":\"223-233\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755686/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2337/db24-0340\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2337/db24-0340","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
已确定的 1 型糖尿病（T1D）患者 C 肽和诊断年龄（AAD）的遗传位点只能解释其变异的一小部分。在此，我们旨在对 T1D 患者的 C 肽和确诊年龄进行大型全基因组关联研究（GWAS），并确定与 C 肽和确诊年龄相关的 HLA 等位基因/单倍型。7,252和7,923名患有T1D的欧洲个体分别被纳入C肽和AAD的GWAS。对 T1D 有强烈保护作用的 HLA-DQB1*06:02 与较高的 C 肽相关。增加 T1D 风险的 HLA-DQB1*03:02、HLADRB1*03:01 和 HLA-A*24:02 与更年轻的 AAD 独立相关。HLA-DR3-DR4 单倍型组合是最强的 T1D 易感因子，与较年轻的 AAD 相关。在 HLA 区域之外，位于 Chr5（GABRG2）上的 rs115673528 与 C 肽相关，而位于 Chr15（CTSH，已知的 T1D 基因座）上的重复序列 rs111970692 与 AAD 相关。基因预测的 CTSH 表达、甲基化和蛋白水平与 AAD 相关；孟德尔随机分析表明，较高水平的前胰蛋白酶 H 可减少 AAD。总之，一些与 T1D 相关的 HLA 等位基因/单倍型也会导致 C 肽和 AAD 的变化。除 HLA 外，T1D 基因位点一般与 C 肽或 AAD 无关。CTSH可能是延缓1型糖尿病发展/恶化的潜在治疗靶点。
Genetics of C-Peptide and Age at Diagnosis in Type 1 Diabetes.
Article highlights: Identified genetic loci for C-peptide and type 1 diabetes (T1D) age at diagnosis (AAD) explain only a small proportion of their variation. We aimed to identify additional genetic loci associated with C-peptide and AAD. Some HLA allele/haplotypes associated with T1D also contributed to variability of C-peptide and AAD, whereas outside the HLA region, T1D loci were mostly not associated with C-peptide or AAD. Genetic variation within CTSH can affect AAD. There is still residual heritability of C-peptide and AAD outside of HLA that could benefit from larger meta-genome-wide association studies.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
