Methylome analysis for spina bifida shows SOX18 hypomethylation as a risk factor with evidence for a complex (epi)genetic interplay to affect neural tube development

Table 1 Top six differentially methylated genes investigated by HM450k and selected for validation with Sequenom EpiTYPER

Gene	Illumina ID	Chr	Mapinfo	WateRmelon		IMA R-package		Gene group
Gene	Illumina ID	Chr	Mapinfo	P value	β diff	P value	β diff	Gene group
ABAT Chr16p13	cg01881182	16	8806531	0.0017	−0.20	0.0047	−0.15	5′ UTR
	cg16586594	16	8806569	0.0005	−0.18	0.0005	−0.19	5′ UTR
	cg08834902	16	8806690	0.0047	−0.23	0.0047	−0.16	5′ UTR
SLC1A6 Chr19p13	cg12695707	19	15121333	0.0002	−0.27	0.0005	−0.16	TSS1500
	cg09470638	19	15121509	0.0010	−0.25	0.0048	−0.14	TSS200
	cg02489552	19	15121531	0.0002	−0.14	0.0002	−0.21	TSS200
SOX18 Chr20q13	cg02231404	20	62679635	0.0010	−0.20	0.0010	−0.21	Body
SOX18 Chr20q13	cg22138735	20	62679713	0.0005	−0.17	0.0005	−0.17	Body
TEPP Chr16q21	cg04370442	16	58019866	0.0047	−0.15	0.0075	−0.16	Body
TEPP Chr16q21	cg12499872	16	58019893	0.0005	−0.31	0.0005	−0.15	Body
CNTNAP1 Chr17q21	cg16308533	17	40838983	0.0005	−0.17	0.0010	−0.19	Body
CNTNAP1 Chr17q21	cg11629889	17	40839022	0.0002	−0.14	0.0010	−0.16	Body
SNED1 Chr2q37	cg23491743	2	241989271	0.0017	−0.16	0.0030	−0.17	Body
SNED1 Chr2q37	cg25241559	2	241989379	0.0005	−0.15	0.0005	−0.17	Body

Selection is performed after analysis with two pipelines and application of three selection criteria: (i) absolute β value difference >0.10; (ii) P value <0.05; and (iii) presence of multiple CpGs per locus. Nucleotide positions accord to NCBI build 37/hg19. Gene group is defined relative to the nearest open reading frame: within 1500 (TSS1500) or 200 bp (TSS200) of a transcription start site, in the 5′ untranslated region (5′ UTR), the first exon of a transcript (exon), in the body of gene (body) or the 3′ UTR (3′ UTR). These six genes were selected for the validation study using Sequenom EpiTYPER
β diff β difference, Chr chromosome, Illumina ID identification according to HM450k, MMC myelomeningocele

ISSN: 1868-7083