Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Cell Rep Med. 2023 Sep 19;4(9):101174. doi: 10.1016/j.xcrm.2023.101174. Epub 2023 Aug 30.
We conduct proteome-wide Mendelian randomization and colocalization analyses to decipher the associations of blood proteins with the risk of type 2 diabetes and diabetic complications. Genetic data on plasma proteome are obtained from 54,306 UK Biobank participants and 35,559 Icelanders. Summary-level data on type 2 diabetes are obtained from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis consortium) consortium (74,124 cases) and FinnGen study (33,043 cases). Data on 10 diabetic complications are obtained from FinnGen and corresponding studies. Among 1,886 proteins, genetically predicted levels of 47 plasma proteins are associated with type 2 diabetes. Eleven of these proteins have strong support of colocalization. Seventeen proteins are associated with at least one diabetic complication, although a few have colocalization support. HLA-DRA, AGER, HSPA1A, and HSPA1B are associated with most microvascular complications. This study reveals causal proteins for the onset of type 2 diabetes and diabetic complications, which enhances the understanding of molecular etiology and development of therapeutics.
我们进行了蛋白质组范围的孟德尔随机化和共定位分析，以破译血液蛋白与 2 型糖尿病和糖尿病并发症风险之间的关联。血浆蛋白质组的遗传数据来自 54306 名英国生物银行参与者和 35559 名冰岛人。2 型糖尿病的汇总水平数据来自 DIAGRAM（糖尿病遗传学复制和荟萃分析联盟）联盟（74124 例）和 FinnGen 研究（33043 例）。10 种糖尿病并发症的数据来自 FinnGen 和相应的研究。在 1886 种蛋白质中，47 种血浆蛋白质的遗传预测水平与 2 型糖尿病相关。其中 11 种蛋白质具有强烈的共定位支持。有 17 种蛋白质与至少一种糖尿病并发症相关，尽管其中一些有共定位支持。HLA-DRA、AGER、HSPA1A 和 HSPA1B 与大多数微血管并发症相关。这项研究揭示了 2 型糖尿病和糖尿病并发症发病的因果蛋白质，这增强了对分子病因和治疗开发的理解。
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