Table 1.

Summary of DNA methylation studies in placenta using genome-wide approaches.

Reference	Method	Population	Sample (n)	Key findings
Finer et al. (2015)	Illumina HM450	UK (South Asian origin)	Term placenta (25 GDM, 18 controls) Cord blood (27 GDM, 21 controls)	More hypermethylated sites observed in both placenta and cord blood samples with GDM compared with the controls 4219 probes and 13,561 probes were differentially methylated between GDM and controls in placental tissue and cord blood respectively. 378 probes were common in placental tissue and cord blood
Hillman et al. (2015)	Illumina HM450	UK	Placenta (23 IUGR, 22 controls) Cord blood (27 IUGR, 18 controls)	No differentially methylated positions were observed in placental tissue between IUGR and controls. 839 differentially methylated regions were revealed in cord blood
Anton et al. (2014)	Illumina HM450	USA (80% African American 20% Other)	Placenta (19 term PE, 12 PTB+PE, 14 controls)	229 and 3411 loci were differentially methylated in PE and PTB+PE in comparison with the controls. Validation of four genes that were differentially methylated by qPCR confirmed altered mRNA expression
Chu et al. (2014)	Illumina HM27	USA	Term placenta (24 PE, 24 controls)	PE samples were hypomethylated compared with controls. Clustering revealed that foetal sex is associated with DNA methylation irrespective of disease state
Liu et al. (2014)	Methylated-CpG island recovery assay (MIRA)	China	Placenta (27 PE, 28 GDM, 30 control)	8191 (2140 genes) and 10,424 (2644 genes) differentially methylated regions were identified in PE and GDM compared with controls respectively 65% of the genes with different methylation revealed concordant changes in methylation between PE and GDM
Ou et al. (2014)	Illumina HM450	China	First-trimester placenta and maternal blood (three of each) Term placenta and maternal blood (two of each)	Identified 2944 and 5218 hypermethylated CpG sites that were foetal specific and found an overlap of 2613 differentially methylated sites between maternal blood and placenta tissue (present in both first- and third-trimester samples)
Petropoulos et al. (2014)	Illumina HM450	Canada	Term placenta (seven GDM, seven controls)	2021 CpG sites (981 genes) were differentially methylated between GDM and controls
Xiang et al. (2014)	MeDIP-Seq and Illumina HM450	China	First-trimester placenta and maternal blood (14 of each)	Using both assays, 3759 CpG sites in 2188 regions were differentially methylated between maternal blood and placenta
Blair et al. (2013)	Illumina HM450	Canada	Third-trimester placenta (20 EOPET, 20 controls)	38,840 CpG sites were altered in EOPET vs controls. Gene expression microarray of a subset of samples (eight of each) showed negative correlation of gene expression changes with DNA methylation alterations
Ruchat et al. (2013)	Illumina HM450	Canada	Term placenta and cord blood (30 GDM, 14 controls)	3271 and 3758 genes were differentially methylated in controls vs GDM in placenta and cord blood, respectively, 25% common to both placenta and cord blood. The genes that were differentially methylated were involved in metabolic disease
Schroeder et al. (2013)	Illumina HM450 and MethylC-Seq & RNA-Seq	USA	Placenta (five first, ten second, 21 third trimester) for 450K Three term placentas for MethylC-Seq	Identified partially methylated domains (PMDs) cover 37% of the placental genome. RNA-seq revealed that genes with PMDs are repressed. 450K data showed that PMDs are conserved throughout gestation
Gordon et al. (2012)	Illumina HM27	Australia	Term placenta (eight MZ, seven DZ pairs)	MZ pairs showed greater similarity in intra-pair DNA methylation than DZ pairs
Jia et al. (2012)	MeDIP+NimbleGen human CpG island promoter microarray (385K)	China	Pooled term (3) compared with pooled PE (3)Validation (nine control, nine PE)	3280 genes differentially methylated between controls and PE. Six genes (CAPN2, EPHX2, ADORA2B, SOX7, CXCL1, CDX1) were validated by bisulphite sequencing
Turan et al. (2012)	Illumina HM27+IlluminaHumanHT-12 v3 Expression BeadChip	USA	Term placenta (48)	Correlated DNA methylation levels with birth weight
Banister et al. (2011)	Illumina HM27	USA	Term placenta (89 SGA, 117 controls)	Identified 22 differentially methylated loci that are associated with SGA
Novakovic et al. (2011b)	Illumina HM27	Australia and Canada	Placenta (18 first, ten second, 14 third trimester)	An increase in overall genome methylation observed from first to third trimester. First-, second- and third-trimester cluster separately on a dendrogram
Lambertini et al. (2011)	MeDIP+Affymetrix Human Tiling Array 2.0R	USA	Term placenta (10 control, 7 IUGR)	Identified 113,020 genome-wide differentially methylated regions
Rakyan et al. (2008)	MeDIP+custom microarray	UK (European)	Term placenta (3)	Identified tissue-specific differentially methylated regions in the placenta

Illumina HM27, Illumina Infinium Human Methylation 27K BeadChip; Illumina HM450, Illumina Infinium Human Methylation 450K BeadChip; MethylC-Seq, whole genome bisulphite sequencing; MeDIP, methylated DNA immunoprecipitation; DZ, dizygotic twins; MZ, monozygotic twins; EOPET, early-onset pre-eclampsia; GDM, gestational diabetes mellitus; IUGR, intrauterine growth restriction; PE, pre-eclampsia; SGA, small for gestational age.