Epigenome wide association study in peripheral blood of pregnant women identifies potential metabolic pathways related to gestational diabetes

Figures & data

Table 1. Clinical characteristic of the subject included in the study.

Comparison	Basal (24/28 weeks)			Pre-Labor (36–38 weeks)			Pos-labour (8 weeks)
	Non-GDM	GDM	P-value	Non-GDM	GDM	P-value	Non-GDM	GDM	P-value
Age	34.2 ± 4.5	33.8 ± 4.1	0.808
Gestational age (weeks)^†	29 ± 3	28 ± 2	0.579	36 ± 2	36 ± 1	0.282
O’sullivan (mg/dl)	160.7 ± 16.3	172.9 ± 22.2	0.085
Weight (Kg)	75.4 ± 11.3	76.0 ± 13.5	0.892	78.7 ± 11.9	76.5 ± 13.1	0.622	71.9 ± 12	67.3 ± 11.5	0.335
Pre-pregnant BMI^†	24.6 ± 6.9	23.8 ± 6.9	0.862
SBP (mm Hg)	104.2 ± 9.9	111.4 ± 15.4	0.131	106.9 ± 12.8	109.1 ± 12.8	0.643	104.1 ± 7.32	108.3 ± 8.9	0.179
DBP (mm Hg)	69.1 ± 8.2	70.1 ± 7.8	0.710	71.2 ± 6.5	73.6 ± 8.8	0.393	78.4 ± 6	75.9 ± 5.4	0.242
Cholesterol (mg/dl)	272 ± 48.1	258.5 ± 51.1	0.446	273.6 ± 49.1	254.7 ± 54	0.308	214.4 ± 15.3	193.5 ± 35.3	0.09
HDL (mg/dl)	82.7 ± 18.2	77.8 ± 15.7	0.424	74.6 ± 12.3	73.2 ± 16.8	0.785	66.3 ± 15.3	58.1 ± 15	0.156
Tg (mg/dl)^†	194 ± 68	183 ± 38	0.829	249 ± 112	242 ± 79	0.749	89 ± 38	61 ± 57	0.890
HbA1C (%)	5.1 ± 0.3	5.3 ± 0.4	0.151	5.3 ± 0.3	5.8 ± 1.6	0.045	5.4 ± 0.3	5.4 ± 0.41	0.756
HOMA-IR^†	1.5 ± 1.1	1.7 ± 1.4	0.147	1.5 ± 1.4	2.1 ± 3.2	0.883	1.0 ± 0.7	0.8 ± 1.3	0.964
Weight_NB (g)							3455 ± 430.7	3309 ± 354.2	0.312
Length_NB (cm)							50.4 ± 1.4	50.3 ± 1.6	0.853
HC_NB (cm)							34.2 ± 1.2	34.1 ± 1.6	0.916
Weight gain (kg)				3.3 ± 1.4	0.49 ± 2.6	0.001

Data are expressed as the mean ± standard deviation or median ± interquartile range (IQR) for variables with no normal distribution. P-values for continuous data were calculated using U-Mann Whitney test. O’sullivan: glucose level in O’sullivan test. BMI: body mass index. HDL: high density lipoprotein cholesterol. SBP: diastolic blood pressure. SBP: systolic blood pressure. Tg: triglycerides. NB: newborn. HC: head circumference. Weight gain: calculated as the difference between the weight at the visit and at basal visit. ^†Median ± IQR.

Figure 1. a) Principal component analysis between GDM (blue, cluster 2) and non-GDM (Red, cluster 1) b) Volcano plot, green: CpGs most hypometylated, red: most hypermethylated, blue: non-significant. c) DMPs according with feature position in the gene d) DMPs according with island position (Cgi position).

Figure 2. a) GO terms most enrichment pval<0.01 b) KEGG pathways most enriched. c)String net PPI (p-value<1.0e-16) with 23 genes related to glucose metabolism.

Table 2. CpGs most correlated to biochemical variables.

CpG	Genes	Variables	r	P value
cg07894331	MAPK1	BMI_p	0.5187	0.002
cg12080079	PAX7	Chl.1	0.5809	0.0005
cg09418268	MTOR	Glucose.0	0.5391	0.001
cg12854232	ERBB4	Glucose.0	−0.5263	0.002
cg20344956	LOC646214	HbA1c.2	0.53	0.003
cg20409752	CAMTA1	HOMAIR.0	−0.5521	0.001
cg07420274	GAD1	HOMAIR.0	−0.5227	0.002
cg14688342	EGFR	OGTT0.2	−0.6216	0.023
cg04217177	ESRRB	OGTT0.2	0.6725	0.01
cg17434154	ESRRG	OGTT0.2	0.5535	0.04
cg21873971	PDIA5	OGTT0.2	0.7919	0.001
cg05894391	PRKAA2	OGTT0.2	0.6177	0.02
cg11055991	PTPRN2	OGTT0.2	0.5803	0.037
cg14479198	RASGRF2	OGTT0.2	−0.5752	0.039
cg19891476	SYK	OGTT0.2	0.5576	0.047
cg13487126	AKT2	OGTT120.2	0.5939	0.032
cg10211745	MINOS1-NBL1	OGTT120.2	0.6742	0.011
cg19234140	MINOS1-NBL1	OGTT120.2	0.6898	0.009
cg14579430	NBL1	OGTT120.2	0.6161	0.024
cg15589641	NBL1	OGTT120.2	0.6261	0.022
cg12474394	NBL1	OGTT120.2	0.6912	0.008
cg14715327	OR4A16	OGTT120.2	0.6704	0.012
cg20230784	GNAQ	OGTT180.0	0.5602	0.0008
cg17816038	CAMTA1	Tg.1	−0.5287	0.002
cg00856432	CACNA1D	VitaminD.2	0.5914	0.0007

r: Spearman correlation. OGTT0: Oral Glucose Tolerance Test first point. OGTT120: Oral Glucose Tolerance Test, point 120 min. OGTT180: Oral Glucose Tolerance Test, point 180 min. Tg: Triglycerides. BMI_p: pre-pregnancy body mass index. Chl: cholesterol levels. .0: basal visit. .1: pre labour visit. .2: post labour visit..

Figure 3. Correlation-plots a)the most correlated CpGs with OGTT0.2 (r>|0.6|). b) the most correlated CpGs with OGTT120.2(r>|0.6|). *: p-value<0.05, **: p-value<0.01, ***: p-value<0.005, ****: p-value<0.001. OGTT0: Fasting glucose; OGTT120: Oral Glucose Tolerance Test, point 120 min. .2: post labour visit.