Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms

Ondičová, Miroslava; Irwin, Rachelle E.; Thursby, Sara-Jayne; Hilman, Luke; Caffrey, Aoife; Cassidy, Tony; McLaughlin, Marian; Lees-Murdock, Diane J.; Ward, Mary; Murphy, Michelle; Lamers, Yvonne; Pentieva, Kristina; McNulty, Helene; Walsh, Colum P.

doi:10.1186/s13148-022-01282-y

Table 1 Top 10 promoter regions with differential methylation show links to neurodevelopmental phenotypes

From: Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms

Promoter^a	Full name	# CG sites	Chr.^b	Position	Mean diff (%)^c	Rank^d	Comb. p val^e	Function/clinical correlates	Reference
ZFP57	Zinc finger protein 57	15	chr6	29648388–29650387	6.23	79	0.011946	Maintains methylation at imprinted genes, many expressed in brain	[82, 83]
[ANKRD20A11P]	Ankyrin repeat domain 20 family, A11, pseudogene	10	chr21	15352259–15354258	3.32	118	0.007401	Pseudogene	–
CES1	Carboxylesterase 1	8	chr16	55866750–55868749	− 3.86	154	0.010683	Hydrolysis or transesterification of various xenobiotics. Hypermethylated in Down syndrome	[43]
DUSP22	Dual specificity phosphatase 22	6	chr6	290130–292129	6.24	192	0.027263	Activator of the JNK signalling pathway. Hypermethylation seen in famine-exposed schizophrenia patients	[73]
MIR4520A; MIR4520B	MicroRNA 4520a/4520b	7	chr17	6558329–6560328	− 7.22	205	0.02862	Hypermethylated in young adults with depression	[35, 84]
HEATR2/PRKAR1B	HEAT repeat containing 2/protein kinase, cAMP-dependent, regulatory, type I, beta	11	chr7	764838–766837	− 2.23	208	0.015631	HEATR-assembly of cilia found in lung & brain; PRKAR1B-expressed in brain, associated with neurodegenerative disorders	[39, 62, 85]
[PTCHD3P2]	Patched domain containing 3 pseudogene 1	1	chr2	170624810–170626809	− 3.69	210	0.029302	Pseudogene	–
PDE4C	Phosphodiesterase 4C, cAMP-specific	1	chr19	18365730–18367729	− 2.05	270	0.009722	Regulation of dopamine D1A receptor signalling; gained methylation in response to B-vit in an RCT w/elderly	[46, 86]
[CNOT6LP1]	CCR4-NOT transcription complex, subunit 6-like	51	chr15	56298875–56300874	− 3.98	293	0.036665	Pseudogene	–
TRIM6-TRIM34	TRIM6-TRIM34 readthrough	10	chr11	5616455–5618454	− 3.77	336	0.039767	Antiretroviral genes	[87, 88]

^aGenes with neural links in bold, pseudogenes in square brackets; ^bChr, chromosome; ^cmean.diff (%), difference in mean β value expressed as %, ^dRank, RnBeads computed ranking value (lowest being best); ^ecomb. p val, combined p value

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ISSN: 1868-7083

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