TABLE 3.

Enriched biological pathways identified based on 788 genes mapped to the CpGs from the EWAS analysis¹

Term	Term description	P value	FDR
GO:0007399	nervous system development2	6.96E−09	1.35E−05
GO:0051094	positive regulation of developmental process	2.68E−08	5.20E−05
GO:0030029	actin filament-based process	6.83E−08	1.33E−04
GO:0048699	generation of neurons2	9.96E−08	1.93E−04
GO:0035295	tube development	1.25E−07	2.43E−04
GO:0045595	regulation of cell differentiation	1.26E−07	2.45E−04
GO:0022008	neurogenesis2	1.38E−07	2.69E−04
GO:0051240	positive regulation of multicellular organismal process	1.59E−07	3.08E−04
GO:0048468	cell development	1.73E−07	3.36E−04
GO:0030182	neuron differentiation2	2.43E−07	4.72E−04
GO:0006928	movement of cell or subcellular component	2.60E−07	5.04E−04
GO:0045597	positive regulation of cell differentiation	4.70E−07	9.11E−04
GO:2000026	regulation of multicellular organismal development	6.12E−07	1.19E−03
GO:0009790	embryo development	9.80E−07	1.90E−03
GO:0051128	regulation of cellular component organization	2.02E−06	3.92E−03
GO:0051960	regulation of nervous system development2	2.37E−06	4.60E−03
GO:0035239	tube morphogenesis	2.40E−06	4.65E−03
GO:0060429	epithelium development	2.66E−06	5.17E−03
GO:0007389	pattern specification process	3.26E−06	6.33E−03
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	5.06E−06	9.82E−03
GO:0050767	regulation of neurogenesis2	6.37E−06	1.24E−02
GO:0006366	transcription from RNA polymerase II promoter	8.03E−06	1.56E−02
GO:0045664	regulation of neuron differentiation2	8.45E−06	1.64E−02
GO:0052697	xenobiotic glucuronidation	9.80E−06	1.90E−02
GO:0010557	positive regulation of macromolecule biosynthetic process	1.07E−05	2.08E−02
GO:1902680	positive regulation of RNA biosynthetic process	1.09E−05	2.11E−02
GO:0072358	cardiovascular system development	1.09E−05	2.12E−02
GO:0072359	circulatory system development	1.09E−05	2.12E−02
GO:0045893	positive regulation of transcription, DNA-templated	1.11E−05	2.16E−02
GO:1903508	positive regulation of nucleic acid–templated transcription	1.11E−05	2.16E−02
GO:0031328	positive regulation of cellular biosynthetic process	1.18E−05	2.28E−02
GO:0060562	epithelial tube morphogenesis	1.19E−05	2.30E−02
GO:0060284	regulation of cell development	1.25E−05	2.42E−02
GO:0048646	anatomical structure formation involved in morphogenesis	1.32E−05	2.56E−02
GO:0009891	positive regulation of biosynthetic process	1.51E−05	2.94E−02
GO:0021915	neural tube development2	1.69E−05	3.28E−02
GO:0051130	positive regulation of cellular component organization	1.87E−05	3.63E−02
GO:0006357	regulation of transcription from RNA polymerase II promoter	1.92E−05	3.73E−02
GO:0050769	positive regulation of neurogenesis2	2.24E−05	4.34E−02
GO:0010628	positive regulation of gene expression	2.28E−05	4.43E−02

¹Gene set enrichment analysis was conducted based on 788 genes that were mapped to the top differentially methylated CpGs (P < 0.001 in the EWAS analysis). The top identified gene ontology (GO) terms are classes of genes that were overly represented in the 788 genes. The P value and false discovery rate (FDR) of enrichment test for each GO term are presented.

²Biological pathways related to nervous system development and its child terms in the GO hierarchy that reached statistical significance (FDR<0.05).