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. 2019 Jun 13;10:2581. doi: 10.1038/s41467-019-10487-4

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Overview of the cross-omics analysis. (1) Methylation quantitative trait loci (meQTL). (2) Expression quantitative trait loci (eQTL). (3) Expression quantitative trait methylation (eQTM). (4) Epigenome-wide association study (EWAS) and Mendelian randomization (MR). (5) Genome-wide association study (GWAS). (6) The association of gene expression expressed in the glucose or insulin metabolism-related tissues and glycemic traits. Results in 1, 2, 3 were extracted from the summary statistics from Biobank-based Integrative Omics Study (BIOS) database (n = 3814). Results in 4 was the results in the current EWAS (discovery phase, n = 4808, replication phase, n = 11,750) and the two-sample Mendelian randomization based on the BIOS database (n = 3814) and GWAS results of Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). Results in 5 was from the GWAS results of MAGIC or the DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM, n = 96,496–452,244). Results in 6 was based on the summary statistics of Genotype-Tissue Expression project (GTEx) and MAGIC or DIAGRAM (n = 153–491)