Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes

Nicolas Fragoso-Bargas; Christian M Page; Bonnie R Joubert; Stephanie J London; Sindre Lee-Ødegård; Julia O Opsahl; Line Sletner; Anne K Jenum; Elisabeth Qvigstad; Rashmi B Prasad; Gunn-Helen Moen; Kåre I Birkeland; Christine Sommer

doi:10.2217/epi-2022-0427

Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes

Epigenomics. 2023 Jan;15(1):39-52. doi: 10.2217/epi-2022-0427. Epub 2023 Mar 28.

Authors

Nicolas Fragoso-Bargas^{1

2}, Christian M Page^{3

4}, Bonnie R Joubert⁵, Stephanie J London⁶, Sindre Lee-Ødegård², Julia O Opsahl², Line Sletner⁷, Anne K Jenum⁸, Elisabeth Qvigstad^{1

2}, Rashmi B Prasad^{9

10}, Gunn-Helen Moen^{2

11

12

13

14}, Kåre I Birkeland^{1

2}, Christine Sommer¹

Affiliations

¹ Department of Endocrinology, Morbid Obesity & Preventive Medicine, Oslo University Hospital, 0424, Oslo, Norway.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318, Oslo, Norway.
³ Centre for Fertility & Health, Norwegian Institute of Public Health, 0403, Oslo, Norway.
⁴ Department of Mathematics, Faculty of Mathematics & Natural Sciences, University of Oslo, 0315, Oslo, Norway.
⁵ Department of Health & Human Services, Population Health Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC 27709, USA.
⁶ Department of Health & Human Services, Epidemiology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
⁷ Department of Pediatric & Adolescents Medicine, Akershus University Hospital, 1478, Lørenskog, Norway.
⁸ Department of General Practice, Institute of Health & Society, University of Oslo, 0318, Oslo, Norway.
⁹ Lund University Diabetes Centre, 214 28, Malmö, Sweden.
¹⁰ Institute for Molecular Medicine Finland FIMM, Helsinki University, 00014, Helsinki, Finland.
¹¹ Institute of Molecular Biosciences, The University of Queensland, St Lucia QLD 4072, Australia.
¹² Department of Public Health & Nursing, K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science & Technology, 7491, Trondheim, Norway.
¹³ The Frazer Institute, The University of Queensland, 4102, Woolloongabba, Australia.
¹⁴ Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1QU, Bristol, United Kingdom.

Abstract

Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans = 302, South Asians = 161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from the MoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.

Keywords: DNA methylation; EPIPREG; EWAS; MoBa; epigenetic epidemiology; epigenetics; folate; pregnancy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

DNA Methylation
Epigenesis, Genetic*
Epigenome*
Fetal Blood / metabolism
Folic Acid / metabolism
Genome-Wide Association Study / methods
Leukocytes

Substances

Folic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding