中国孕妇妊娠糖尿病常见基因变异的鉴定和潜在临床应用

IF 6.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Claudia Ha-Ting Tam, Ying Wang, Chi Chiu Wang, Lai Yuk Yuen, Cadmon King-Poo Lim, Junhong Leng, Ling Wu, Alex Chi-Wai Ng, Yong Hou, Kit Ying Tsoi, Hui Wang, Risa Ozaki, Albert Martin Li, Qingqing Wang, Juliana Chung-Ngor Chan, Yan Chou Ye, Wing Hung Tam, Xilin Yang, Ronald Ching-Wan Ma
{"title":"中国孕妇妊娠糖尿病常见基因变异的鉴定和潜在临床应用","authors":"Claudia Ha-Ting Tam, Ying Wang, Chi Chiu Wang, Lai Yuk Yuen, Cadmon King-Poo Lim, Junhong Leng, Ling Wu, Alex Chi-Wai Ng, Yong Hou, Kit Ying Tsoi, Hui Wang, Risa Ozaki, Albert Martin Li, Qingqing Wang, Juliana Chung-Ngor Chan, Yan Chou Ye, Wing Hung Tam, Xilin Yang, Ronald Ching-Wan Ma","doi":"10.4093/dmj.2024.0139","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.</p><p><strong>Methods: </strong>We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.</p><p><strong>Results: </strong>Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.</p><p><strong>Conclusion: </strong>Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women.\",\"authors\":\"Claudia Ha-Ting Tam, Ying Wang, Chi Chiu Wang, Lai Yuk Yuen, Cadmon King-Poo Lim, Junhong Leng, Ling Wu, Alex Chi-Wai Ng, Yong Hou, Kit Ying Tsoi, Hui Wang, Risa Ozaki, Albert Martin Li, Qingqing Wang, Juliana Chung-Ngor Chan, Yan Chou Ye, Wing Hung Tam, Xilin Yang, Ronald Ching-Wan Ma\",\"doi\":\"10.4093/dmj.2024.0139\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.</p><p><strong>Methods: </strong>We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.</p><p><strong>Results: </strong>Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.</p><p><strong>Conclusion: </strong>Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.</p>\",\"PeriodicalId\":11153,\"journal\":{\"name\":\"Diabetes & Metabolism Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes & Metabolism Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4093/dmj.2024.0139\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes & Metabolism Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4093/dmj.2024.0139","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

背景:妊娠期高血糖的遗传基础仍不清楚。本研究旨在揭示妊娠糖尿病(GDM)的遗传决定因素并研究其应用:我们对中国妇女(464 例病例和 1,217 例对照)的 GDM 全基因组关联研究(GWAS)进行了荟萃分析,随后在一个独立的中国队列(564 例病例和 572 例对照)中进行了从头复制,并在欧洲(12,332 例病例和 131,109 例对照)和多种族人群(5,485 例病例和 347,856 例对照)中进行了硅复制。根据确定的变体得出了多基因风险评分(PRS):利用全基因组扫描和候选基因方法,我们确定了四个 GDM 易感基因位点。结果:通过全基因组扫描和候选基因方法,我们确定了四个 GDM 的易感基因位点,其中包括之前报道的三个 GDM 和 2 型糖尿病 (T2DM) 的易感基因位点:MTNR1B(rs7945617,几率比 [OR],1.64;95% 置信区间 [CI],1.38 至 1.96])、CDKAL1(rs7754840,OR,1.33;95% CI,1.13 至 1.58)和 INS-IGF2-KCNQ1(rs2237897,OR,1.48;95% CI,1.23 至 1.79),以及 TBR1-SLC4A10 附近的一个新的全基因组显著位点(rs117781972,OR,2.05;95% CI,1.61 至 2.62;Pmeta=7.6×10-9),该位点以前从未在 T2DM 或血糖特征的 GWAS 中报道过。此外,我们还发现,与其他个体相比,PRS 高(最高五分位数)的妇女妊娠后发生 GDM 和糖耐量异常的风险分别高出三倍(95% CI,2.30 至 4.09;Pmeta=3.1×10-14)和 71%(95% CI,1.08 至 2.71;P=0.0220):我们的研究结果表明,葡萄糖代谢的遗传结构在妊娠和非妊娠状态下既有相似之处,也有不同之处。整合遗传信息有助于识别罹患 GDM 或糖尿病风险较高的孕妇。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.

Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.

Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.

Conclusion: Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Diabetes & Metabolism Journal
Diabetes & Metabolism Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
10.40
自引率
6.80%
发文量
92
审稿时长
52 weeks
期刊介绍: The aims of the Diabetes & Metabolism Journal are to contribute to the cure of and education about diabetes mellitus, and the advancement of diabetology through the sharing of scientific information on the latest developments in diabetology among members of the Korean Diabetes Association and other international societies. The Journal publishes articles on basic and clinical studies, focusing on areas such as metabolism, epidemiology, pathogenesis, complications, and treatments relevant to diabetes mellitus. It also publishes articles covering obesity and cardiovascular disease. Articles on translational research and timely issues including ubiquitous care or new technology in the management of diabetes and metabolic disorders are welcome. In addition, genome research, meta-analysis, and randomized controlled studies are welcome for publication. The editorial board invites articles from international research or clinical study groups. Publication is determined by the editors and peer reviewers, who are experts in their specific fields of diabetology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信