Additional file 3 of Integrated epigenome, whole genome sequence and metabolome analyses identify novel multi-omics pathways in type 2 diabetes: a Middle Eastern study

Additional file 3: Figure S1. Full omics network of CpG-metabolites and associated SNP-CpGs and associated metabolite-metabolite pairs

Additional file 1 of Integrated epigenome, whole genome sequence and metabolome analyses identify novel multi-omics pathways in type 2 diabetes: a Middle Eastern study

Additional file 1. Methods

Additional file 2 of Integrated epigenome, whole genome sequence and metabolome analyses identify novel multi-omics pathways in type 2 diabetes: a Middle Eastern study

Additional file 2: Table S1. Results of two way discovery replication T2D EWAS using cohorts 1 and 2. Table S2. Results of lookup of the identified 66 T2D CpGs in databases and previous literature. Table S3. Replication of literature findings. Table S4. eQTM at FDR < 0.05 from BIOS QTL site for all 66 T2D CpGs. Table S5. KEGG pathway (Pathways relevant to diabetes or complications are highlighted). Table S6. All 688 CpG-SNP significant associations in 27 loci. Table S7. GWAS associations for the SNPs in the neighborhood of meQTL SNPs as reported in the GWAS catalogue. Table S8. GWAS associations for the SNPs in the neighborhood of meQTL SNPs as reported in the Stanford bio bank. Table S9. A)Discovery and Replication cohorts for T2D MWAS, B)T2D significant metabolites with the discovery and replication statistics. Table S10. 77 CpG-metabolite association results from meta-analysis (11 colored rows are associations with high heterogeneity (p<0.05)). Table S11. Associations of 16 metabolites from the multi-omics network with BMI, lipoproteins and triglycerides. Table S12. Characteristics of metabolomics samples used for the T2D MWAS

Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits

Clinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report a genome-wide association study with 45 clinically relevant traits from the population of Qatar using a whole genome sequencing approach in a discovery set of 6218 individuals and replication in 7768 subjects. Trait heritability is more similar between Qatari and European populations (r = 0.81) than with Africans (r = 0.44). We identify 281 distinct variant-trait-associations at genome wide significance that replicate known associations. Allele frequencies for replicated loci show higher correlations with European (r = 0.94) than with African (r = 0.85) or Japanese (r = 0.80) populations. We find differences in linkage disequilibrium patterns and in effect sizes of the replicated loci compared to previous reports. We also report 17 novel and Qatari-predominate signals providing insights into the biological pathways regulating these traits. We observe that European-derived polygenic scores (PGS) have reduced predictive performance in the Qatari population which could have implications for the translation of PGS between populations and their future application in precision medicine.Other Information Published in: Nature Communications License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41467-021-21381-3</p

Table_1_Identification of distinct circulating microRNAs in acute ischemic stroke patients with type 2 diabetes mellitus.XLSX

Stroke is the second leading cause of global mortality and continued efforts aim to identify predictive, diagnostic, or prognostic biomarkers to reduce the disease burden. Circulating microRNAs (miRNAs) have emerged as potential biomarkers in stroke. We performed comprehensive circulating miRNA profiling of ischemic stroke patients with or without type 2 diabetes mellitus (T2DM), an important risk factor associated with worse clinical outcomes in stroke. Serum samples were collected within 24 h of acute stroke diagnosis and circulating miRNAs profiled using RNA-Seq were compared between stroke patients with T2DM (SWDM; n = 92) and those without T2DM (SWoDM; n = 98). Our analysis workflow involved random allocation of study cohorts into discovery (n = 96) and validation (n = 94) datasets. Five miRNAs were found to be differentially regulated in SWDM compared to SWoDM patients. Hsa-miR-361-3p and -664a-5p were downregulated, whereas miR-423-3p, -140-5p, and -17-3p were upregulated. We also explored the gene targets of these miRNAs and investigated the downstream pathways associated with them to decipher the potential pathways impacted in stroke with diabetes as comorbidity. Overall, our novel findings provide important insights into the differentially regulated miRNAs, their associated pathways and potential utilization for clinical benefits in ischemic stroke patients with diabetes.</p