Diabetes risk loci-associated pathways are shared across metabolic tissues

被引:0
|
作者
Bouland, Gerard A. [1 ]
Beulens, Joline W. J. [2 ,3 ]
Nap, Joey [1 ]
van der Slik, Arno R. [4 ]
Zaldumbide, Arnaud [1 ]
't Hart, Leen M. [1 ,2 ,5 ]
Slieker, Roderick C. [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Cell & Chem Biol, Einthovenweg 20, NL-2333 ZC Leiden, Netherlands
[2] Amsterdam Publ Hlth Inst, Locat VUMC, Amsterdam UMC, Dept Epidemiol & Data Sci, Amsterdam, Netherlands
[3] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
[4] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Dept Biomed Data Sci, Mol Epidemiol Sect, Leiden, Netherlands
关键词
Type; 2; diabetes; SNPs; Pathways; Metabolism; GENOME-WIDE ASSOCIATION; PROTEIN-SYNTHESIS; MUSCLE RIBOSOMES; MECHANISMS; REVEALS; GENES; RNA;
D O I
10.1186/s12864-022-08587-5
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aims/hypothesis Numerous genome-wide association studies have been performed to understand the influence of genetic variation on type 2 diabetes etiology. Many identified risk variants are located in non-coding and intergenic regions, which complicates understanding of how genes and their downstream pathways are influenced. An integrative data approach will help to understand the mechanism and consequences of identified risk variants. Methods In the current study we use our previously developed method CONQUER to overlap 403 type 2 diabetes risk variants with regulatory, expression and protein data to identify tissue-shared disease-relevant mechanisms. Results One SNP rs474513 was found to be an expression-, protein- and metabolite QTL. Rs474513 influenced LPA mRNA and protein levels in the pancreas and plasma, respectively. On the pathway level, in investigated tissues most SNPs linked to metabolism. However, in eleven of the twelve tissues investigated nine SNPs were linked to differential expression of the ribosome pathway. Furthermore, seven SNPs were linked to altered expression of genes linked to the immune system. Among them, rs601945 was found to influence multiple HLA genes, including HLA-DQA2, in all twelve tissues investigated. Conclusion Our results show that in addition to the classical metabolism pathways, other pathways may be important to type 2 diabetes that show a potential overlap with type 1 diabetes.
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页数:9
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