Exploring the Epigenetic Regulatory Role of m6A-Associated SNPs in Type 2 Diabetes Pathogenesis

Figures & data

Table 1 The 20 Most Important m6A-SNPs Related to T2D

Variant	CHR	Position	P. value	Gene	Confidence_Level	eQTL Hits	DEG	Methylation Type	Allele Frequency
rs1801206	4	6302707	4.90E-39	WFS1	Prediction:(Low)	8 hits	No	m6A	5.76E-01
rs116234738	5	102537357	1.40E-27	PPIP5K2	Prediction:(Low)	0 hit	Yes	m6A	3.07E-02
rs5213	11	17408404	1.90E-26	KCNJ11	MeRIP-Seq:(Medium)	16 hits	Yes	m6A	7.18E-01
rs750625	8	41525914	1.90E-25	ANK1	Prediction:(Low)	3 hits	No	m6A	6.57E-06
rs10832778	11	17394073	8.50E-23	NCR3LG1	Prediction:(Low)	26 hits	No	m6A	7.09E-01
rs9379084	6	7231843	2.30E-20	RREB1	MeRIP-Seq:(Medium)	1 hit	Yes	m6A	9.19E-02
rs12590	10	12292348	5.50E-17	CDC123	Prediction:(Low)	2 hits	No	m6A	1.50E-01
rs3743481	15	77907145	1.60E-16	LINGO1	MeRIP-Seq:(Medium)	1 hit	No	m6A	4.42E-01
rs2641348	1	120437884	5.60E-16	ADAM30	Prediction:(Low)	6 hits	No	m6A	1.69E-01
rs6685892	1	120458004	6.20E-16	NOTCH2	Prediction:(Low)	5 hits	No	m6A	1.68E-01
rs2793823	1	120437718	7.30E-15	ADAM30	Prediction:(Low)	3 hits	No	m6A	2.70E-01
rs11553326	4	724884	5.50E-12	PCGF3	Prediction:(Low)	7 hits	No	m6A	3.21E-02
rs2308891	6	32610009	1.40E-11	HLA-DQA1	Prediction:(Low)	293 hits	No	m6A	2.44E-02
rs3760471	17	4069735	2.80E-11	ANKFY1	Prediction:(Low)	5 hits	Yes	m6A	1.38E-04
rs1058129	15	77905661	4.30E-11	LINGO1	Prediction:(Low)	5 hits	No	m6A	7.06E-01
rs7250850	19	47585517	9.70E-11	ZC3H4	Prediction:(Low)	1 hit	No	m6A	5.23E-01
rs1046080	6	31595882	1.30E-10	PRRC2A	miCLIP:(High)	38 hits	No	m6A	7.43E-01
rs1033500	6	32307382	3.00E-10	C6orf10	Prediction:(Low)	21 hits	No	m6A	3.37E-01
rs2227956	6	31778272	3.10E-10	HSPA1L	Prediction:(Low)	112 hits	No	m6A	8.77E-01
rs4993986	6	32627652	6.10E-09	HLA-DQB1	miCLIP:(High)	1 hit	Yes	m6A	3.69E-01

Figure 1 Design and main implementation steps of this study.

Figure 2 Identification of T2D related m6A-SNPs. (A) The identified T2D related m6A-SNPs with genome-wide significance are displayed in the Manhattan plot. P < 5.0e−05 was set as the suggestive threshold, and p < 5.0e-08 was set as the genome-wide threshold. (B) GO enrichment analysis of the T2D related m6A-SNPs (p < 5.0e-05). (C) Gene expression differences between T2D patients and controls in islet (GSE38642), adipose (GSE78721), and liver tissue (GSE23343).

Figure 3 Integrated analysis of the leading m6A-SNP rs4993986. (A) The protein coding region of rs4993986 in HLA-DQB1 gene sequence shows high transcriptional activity and DNaseI hypersensitivity. RNA-binding protein analysis revealed that rs4993986 exhibited a binding region to the RBP PABPC1. (B) Prediction of m6A modification on the HLA-DQB1 transcript (ENST00000434651.6) on the SRAMP website. (C) The secondary structure of HLA-DQB1 transcript and the position of rs4993986 near the m6A modification site. (D) The expression of HLA-DQB1 (H2-Ab1) was identified in the mouse pancreas scRNA-seq data. Violin plot shows that HLA-DQB1 expression is increased in diabetic islet acinar cells. (E) HLA-DQB1 expression of different cell types in islet of diabetes and control group.