SLC9B1 methylation predicts fetal intolerance of labor

Figures & data

Table 1. Cohort demographics for women with samples collected between 24–32 weeks gestation (n = 57).

	Fetal Intolerance Mean±SD	Control Mean±SD	P value
Maternal Age	25.97±4.1	25.2±4.5	NS
GA at Sample Collection	26.8±2.2	27.3±2.3	NS
GA at Birth	38.6±1.8	38.6±2.9	NS
	Fetal Intolerance (%) (n = 12)	Control (%) (n = 45)	P value
Cesarean Section	83.3	11.1	2.70 × 10^−5
Hypertension	16.7	13.3	NS
Maternal Smoking^a	8.3	6.81	NS

^a Missing data for one subject. Those experiencing fetal intolerance of labor were more likely to have a Cesarean section. No other characteristic differed by group. SD: Standard deviation. NS: non-significant.

Figure 1. Manhattan plot showing the association of CpG sites across the genome. Each CpG site that passed quality control was assessed for associations with fetal intolerance of labor. Sites falling above the horizontal line indicate experiment-wide significance. The x-axis represents the chromosome number and the y-axis is the negative log of the P value, which is indicative of the significance level. The plot is further zoomed in to chromosome four, and the SLC9B1 gene. In the gene diagram, yellow boxes represent exons and the green box represents the location of the CpG island. The heatmap indicates the correlation between CpG sites.

Table 2. CpG sites significantly associated with fetal intolerance of labor.

CpG site	Gene Symbol	Position	T statistic	P value	FDR
cg21197425	SLC9B1	chr4: 103940854	7.70	2.69 × 10^−10	9.58 × 10^−05
cg05605371	SLC9B1	chr4: 103940876	7.29	1.25 × 10^−9	1.40 × 10^−04
cg19672271	SLC9B1	chr4: 103940878	7.48	6.05 × 10^−10	9.58 × 10^−05
cg06999381	SLC9B1	chr4: 103940936	7.47	6.40 × 10^−10	9.58 × 10^−05

FDR was computed using the Benjamini-Hochberg method. Coordinates are based on GRCh37/hg19.

Figure 2. DNA methylation associates with fetal intolerance of labor. (A) DNA methylation of cg06999381 associates with fetal intolerance of labor between 24–32 weeks gestation in the original cohort, (B) Association with fetal intolerance of labor in the replication cohort, (C) Receiver operator characteristic curve, (D) DNA methylation associates with gene expression over pregnancy (ILMN_1724931). Red indicates fetal intolerance to labor. Open circles are samples from visit 1, closed circles are samples from visit 2. All associations are statistically significant (P<0.05).