Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci.
Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci.
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DOI：
10.1038/s42003-021-02368-8
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发表时间：
2021-07-23
影响因子：
5.9
通讯作者：
Hakonarson H
中科院分区：
文献类型：
--
作者：
Qu HQ;Qu J;Bradfield J;Marchand L;Glessner J;Chang X;March M;Li J;Connolly JJ;Roizen JD;Sleiman P;Polychronakos C;Hakonarson H
遗传风险分数(GRS)低的1型糖尿病(T1D)患者可能是非自身免疫的，也可能是由其他基因座介导的自身免疫。T1D-GRS2为我们提供了一个研究这些患者的遗传结构的机会。共有18,949名欧洲人参加了这项研究，其中包括6599例T1D病例和12,323名对照。957例(14.5%)T1D患者存在低GRS(GRS <； 8.43)。对这些患者进行的全基因组关联研究确定了41个未报告的基因座。本研究共鉴定出2个常见变异基因座和39个稀有变异基因座。这项研究发现了与低GRS T1D和干扰素-α诱导的MNDA基因表达水平相关的常见SNP，表明病毒感染在T1D中所起的作用。有趣的是，之前的研究发现，在41个未报道的基因座中，有16个与自闭症谱系障碍(ASD)有关，这表明这些基因座上的基因可能同时导致了T1D和自闭症。曲惠琪等人。提出了一项病例对照关联研究，以检查遗传风险分数低的欧洲1型糖尿病(T1D)患者的遗传结构。他们确定了41个与低遗传风险分数的T1D相关的基因座，包括以前与病毒感染和自闭症谱系障碍有关的区域，总共为T1D的发病机制提供了进一步的洞察。
Type 1 diabetes (T1D) patients with low genetic risk scores (GRS) may be non-autoimmune or autoimmune mediated by other genetic loci. The T1D-GRS2 provides us an opportunity to look into the genetic architecture of these patients. A total of 18,949 European individuals were included in this study, including 6599 T1D cases and 12,323 controls. 957 (14.5%) T1D patients were identified with low GRS (GRS < 8.43). The genome-wide association study on these patients identified 41 unreported loci. Two loci with common variants and 39 loci with rare variants were identified in this study. This study identified common SNPs associated with both low GRS T1D and expression levels of the interferon-α-induced MNDA gene, indicating the role of viral infection in T1D. Interestingly, 16 of the 41 unreported loci have been linked to autism spectrum disorder (ASD) by previous studies, suggesting that genes residing at these loci may underlie both T1D and autism. Hui-Qi Qu et al. present a case-control association study to examine the genetic architecture of European patients with type 1 diabetes (T1D) of low genetic risk score. They identify 41 loci associated with T1D of low genetic risk score, including regions previously linked to viral infection and autism spectrum disorder, altogether providing further insight into the pathogenesis of T1D.
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影响因子：
30.8
作者：
Krumm, Niklas;Turner, Tychele N.;Baker, Carl;Vives, Laura;Mohajeri, Kiana;Witherspoon, Kali;Raja, Archana;Coe, Bradley P.;Stessman, Holly A.;He, Zong-Xiao;Leal, Suzanne M.;Bernier, Raphael;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
7.7
作者：
Paterson AD;Waggott D;Boright AP;Hosseini SM;Shen E;Sylvestre MP;Wong I;Bharaj B;Cleary PA;Lachin JM;MAGIC (Meta-Analyses of Glucose and Insulin-related traits Consortium);Below JE;Nicolae D;Cox NJ;Canty AJ;Sun L;Bull SB;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
通讯作者：
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
9.8
作者：
Ahola-Olli, Ari V.;Wurtz, Peter;Raitakari, Olli T.
通讯作者：
Raitakari, Olli T.