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全基因组关联分析揭示糖尿病新亚型的病因学差异
2021-11-07 13:12

瑞典隆德大学Emma Ahlqvist团队利用全基因组关联分析揭示糖尿病新亚型的病因学差异。相关论文于2021年11月4日在线发表在《自然—遗传学》杂志上。

研究人员使用全基因组关联和遗传风险评分(GRS)分析来比较了潜在的遗传驱动因素。来自瑞典ANDIS(All New Diabetics In Scania)研究的个体与无糖尿病的个体进行了比较;芬兰DIREVA(Diabetes register in Vasa)和Botnia研究被用来进行重复。结果表明,亚型在糖尿病家族史和与糖尿病相关特征的GRS方面存在差异。严重的胰岛素抵抗亚型与空腹胰岛素的GRS独特相关,但与TCF7L2基因座的变体或反映胰岛素分泌的GRS无关。

此外,LRMDA附近的一个SNP(rs10824307)与轻度肥胖相关的糖尿病有唯一的关联。因此,研究人员得出结论,这些亚型具有部分不同的遗传背景,并表明了病因学上的差异。

据悉,2型糖尿病已被可重复地归纳为5个亚型,具有不同的疾病进展和并发症风险;然而,病因学差异尚不清楚。

附:英文原文

Title: Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes

Author: Mansour Aly, Dina, Dwivedi, Om Prakash, Prasad, Rashmi B., Krjmki, Annemari, Hjort, Rebecka, Thangam, Manonanthini, kerlund, Mikael, Mahajan, Anubha, Udler, Miriam S., Florez, Jose C., McCarthy, Mark I., Brosnan, Julia, Melander, Olle, Carlsson, Sofia, Hansson, Ola, Tuomi, Tiinamaija, Groop, Leif, Ahlqvist, Emma

Issue&Volume: 2021-11-04

Abstract: Type 2 diabetes has been reproducibly clustered into five subtypes with different disease progression and risk of complications; however, etiological differences are unknown. We used genome-wide association and genetic risk score (GRS) analysis to compare the underlying genetic drivers. Individuals from the Swedish ANDIS (All New Diabetics In Scania) study were compared to individuals without diabetes; the Finnish DIREVA (Diabetes register in Vasa) and Botnia studies were used for replication. We show that subtypes differ with regard to family history of diabetes and association with GRS for diabetes-related traits. The severe insulin-resistant subtype was uniquely associated with GRS for fasting insulin but not with variants in the TCF7L2 locus or GRS reflecting insulin secretion. Further, an SNP (rs10824307) near LRMDA was uniquely associated with mild obesity-related diabetes. Therefore, we conclude that the subtypes have partially distinct genetic backgrounds indicating etiological differences. Genome-wide association and genetic risk score analyses highlight differences in genetic architecture across five subtypes of diabetes.

DOI: 10.1038/s41588-021-00948-2

Source: https://www.nature.com/articles/s41588-021-00948-2

 

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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