Table 3.
Putative Role of the associated variants with T2D in studied population (North-west India) utilizing the information from the various databases including GTEX, UCSC genome browser and HSF.
| Variant | Location of the variant w.r.t nearest gene | Allele Ref/Alt (Risk allele)* | eQTL gene | eQTL Tissue | eQTL sample size | eQTL NES | eQTL p-value | eQTL m-value | Putative role (cis- eQTL) of variant | Regulatory role of variant (ENCODE and Haploreg data) | Splicing effect28,46 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| rs9419958 | 1st intron variant of OBFC1/STN1 | T/C (C) | OBFC1/STN1 | Pancreas | 220 | 0.221 | 1.9E-3 | 1 | Significant and Up regulation | H3K27ac_Enh/H3K4me3_Pro / H3K4me1_Enh/ H3K9ac_Pro/7_Enh/4_PromD2/TSSA/9_Txresg | Creation of ESE intronic site/ SF2/ASF (IgM-BRCA1)-91.23 |
| Adipose-subcutaneous | 385 | 0.226 | 1.1E-4 | 1 | Significant and Up regulation | H3K27ac_Enh/H3K4me3_Pro / H3K4me1_Enh/ H3K9ac_Pro/TSSAFlnk/3_PromD1 | |||||
| Skeletal Muscle | 491 | 0.0057 | 0.9 | 0 | Non-Significant | H3K27ac_Enh/H3K4me3_Pro / H3K4me1_Enh/ H3K9ac_Pro/TSSAFlnk/3_PromD1 | |||||
| rs4783704 | intergenic variant of TERF2 and CYB5B | C/T (C) | N/A | Pancreas | N/A | N/A | N/A | N/A | N/A | 22_PromP | Creation of ESE intronic site/ Creation of new site for SRp55–86.86 and 9G8–60.67 |
| Adipose-subcutaneous | H3K27ac_Enh/ H3K4me1_Enh/14_EnhA2 | ||||||||||
| Skeletal Muscle | H3K27ac_Enh/ H3K9ac_Pro/16_EnhW1 | ||||||||||
| Transcription factors binding sites including TCF7L2, TCF12; DNase hypersensitive # | |||||||||||
| rs16847897 | upstream to TERC; 7th intron variant of LRRC31 | G/C (C) | LRRC34 | Pancreas | 220 | −0.169 | 0.1 | 0.924 | Non-Significant | No Role w.r.t studied tissues | Creation of binding site for SF2/ASF (IgM-BRCA1)-75.85 and SRp55 site broken-100 |
| Adipose-subcutaneous | 385 | −0.208 | 3.7E-5 | 1 | Significant and Down regulation | ||||||
| Skeletal Muscle | 491 | −0.139 | 0.03 | 0.965 | Significant and Down regulation | ||||||
| rs10936599 | upstream to TERC; exon variant of MYNN | C/T (C) | LRRC34 | Pancreas | 220 | −0.02 | 0.9 | 0.298 | Non-Significant |
H3K27ac_Enh/H3K4me3_Pro/ H3K4me1_Enh/H3K9ac_Pro (Pancreas) H3K27ac_Enh/H3K4me3_Pro/ H3K4me1_Enh/H3K9ac_Pro (Adipose-subcutaneous) H3K27ac_Enh/H3K4me3_Pro/ H3K4me1_Enh/H3K9ac_Pro (Skeletal Muscle) |
Creation of ESE intronic site/Creation of new site for SRp40–82.10 and SC35–82.42 |
| Adipose-subcutaneous | 385 | −0.28 | 7.6E-8 | 1 | Significant and Down regulation | ||||||
| Skeletal Muscle | 491 | −0.123 | 0.07 | 0.841 | Non-Significant | ||||||
| MYNN | Pancreas | 220 | 0.171 | 0.05 | 0.938 | Non-Significant | |||||
| Adipose-subcutaneous | 385 | 0.099 | 0.03 | 0.97 | Significant and Up regulation | ||||||
| Skeletal Muscle | 491 | 0.106 | 2.2E-3 | 0.99 | Significant and Up regulation | ||||||
| rs74019828 | 4th intron variant of CSNK2A2 | G/A (G) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | No Role w.r.t studied tissues | Creation of new binding site for SC35–75.17 |
*Risk allele in this study; NES – Normalized Effect Size in eQTL; m-value – posterior probability that effect exists in each tissue, ranges between 0 and 1; H3K27Ac_Enh – chemical modification (acetylation) of the histone proteins (H3) at lysine 27 and associated with transcriptional initiation and open chromatin structure (active enhancer); H3K4me3 – chemical modification (methylation) of the histone proteins (H3) at lysine 4, marks promoters that are active or poised to be activated; H3K4me1 – chemical modification (methylation) of the histone proteins (H3) at lysine 4 and is associated with enhancers, and downstream of transcription starts.; H3K9ac – chemical modification (acetylation) of the histone proteins (H3) at lysine 9 and is associated with transcriptional initiation and open chromatin structure; Enh – Enhancers; Pro – Promoters; TSSA – active transcription start site; TxReg – transcription regulatory; PromD1 – promoter downstream TSS; TSSAFlk – Flanking TSS; 22PromP – poised promoter; EnhW1 – weak enhancer; EnhA2 – active enhancer 2; the H3K4me1/2/3 and H3K36me2/3 are linked with genomic region which actively transcribing and H3K9me3, H3K27me3 and H4K20me3 with non-transcribing region; ESE – Exonic Splicing Enhancers; SR – Serine-Arginine rich proteins; 9G8, SC35 – SR splicing factor; SF2/ASF (IgM-BRCA1) – Serine-Arginine rich proteins; #Supplementary Fig. S1.