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1. Correction: Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization (The Pharmacogenomics Journal, (2020), 10.1038/s41397-019-0140-y)

Author

King, C. (Charlotte), McKenna, A. (Amanda), Farzan, N. (Niloufar), Vijverberg, S.J.H. (Susanne), Schee, M.P. (Marc P.) van der, Maitland-van der Zee, A-H. (Anke-Hilse), Arianto, L. (Lambang), Bisgaard, H. (Hans), BØnnelykke, K. (Klaus), Berce, V. (Vojko), PotoČnik, U. (Uros), Repnik, K. (Katja), Carleton, B.C. (Bruce), Daley, D. (Denise), Chew, F.T. (Fook Tim), Chiang, W.C. (Wen Chin), Sio, Y.Y. (Yang Yie), Cloutier, M.M. (Michelle M.), Dekker, H.T. (Herman) den, Duijts, L. (Liesbeth), Jongste, J.C. (Johan) de, Dijk, F.N. (F. Nicole), Flores, C. (Carlos), Hernandez-Pacheco, N. (Natalia), Mukhopadhyay, S. (Somnath), Basu, K. (Kaninika), Tantisira, K.G. (Kelan G.), Verhamme, K.M.C. (Katia), Celedón, J.C. (Juan C.), Forno, E. (Erick), Canino, G. (Glorisa), Francis, B. (Ben), Pirmohamed, M. (Munir), Sinha, I. (Ian), Hawcutt, D.B. (Daniel B.), King, C. (Charlotte), McKenna, A. (Amanda), Farzan, N. (Niloufar), Vijverberg, S.J.H. (Susanne), Schee, M.P. (Marc P.) van der, Maitland-van der Zee, A-H. (Anke-Hilse), Arianto, L. (Lambang), Bisgaard, H. (Hans), BØnnelykke, K. (Klaus), Berce, V. (Vojko), PotoČnik, U. (Uros), Repnik, K. (Katja), Carleton, B.C. (Bruce), Daley, D. (Denise), Chew, F.T. (Fook Tim), Chiang, W.C. (Wen Chin), Sio, Y.Y. (Yang Yie), Cloutier, M.M. (Michelle M.), Dekker, H.T. (Herman) den, Duijts, L. (Liesbeth), Jongste, J.C. (Johan) de, Dijk, F.N. (F. Nicole), Flores, C. (Carlos), Hernandez-Pacheco, N. (Natalia), Mukhopadhyay, S. (Somnath), Basu, K. (Kaninika), Tantisira, K.G. (Kelan G.), Verhamme, K.M.C. (Katia), Celedón, J.C. (Juan C.), Forno, E. (Erick), Canino, G. (Glorisa), Francis, B. (Ben), Pirmohamed, M. (Munir), Sinha, I. (Ian), and Hawcutt, D.B. (Daniel B.)

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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2. Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation

Author

King, C. (Charlotte), McKenna, A. (Amanda), Farzan, N. (Niloufar), Vijverberg, S.J.H. (Susanne), Schee, M.P. (Marc P.) van der, Maitland-van der Zee, A-H. (Anke-Hilse), Arianto, L. (Lambang), Bisgaard, H. (Hans), BØnnelykke, K. (Klaus), Berce, V. (Vojko), Potočnik, U. (Uroš), Repnik, K. (Katja), Carleton, B.C. (Bruce), Daley, D. (Denise), Chew, F.T. (Fook Tim), Chiang, W.C. (Wen Chin), Sio, Y.Y. (Yang Yie), Cloutier, M.M. (Michelle M.), Dekker, H.T. (Herman) den, Duijts, L. (Liesbeth), Jongste, J.C. (Johan) de, Dijk, F.N. (F. Nicole), Koppelman, G.H. (Gerard), Flores, C. (Carlos), Hernandez-Pacheco, N. (Natalia), Pino-Yanes, M. (Maria), Mukhopadhyay, S. (Somnath), Basu, K. (Kaninika), Bignell, L. (Lauren), Tantisira, K.G. (Kelan G.), Turner, S.W. (Steve), Verhamme, K.M.C. (Katia), Francis, B. (Ben), Pirmohamed, M. (Munir), Sinha, I. (Ian), Hawcutt, D.B. (Daniel B.), King, C. (Charlotte), McKenna, A. (Amanda), Farzan, N. (Niloufar), Vijverberg, S.J.H. (Susanne), Schee, M.P. (Marc P.) van der, Maitland-van der Zee, A-H. (Anke-Hilse), Arianto, L. (Lambang), Bisgaard, H. (Hans), BØnnelykke, K. (Klaus), Berce, V. (Vojko), Potočnik, U. (Uroš), Repnik, K. (Katja), Carleton, B.C. (Bruce), Daley, D. (Denise), Chew, F.T. (Fook Tim), Chiang, W.C. (Wen Chin), Sio, Y.Y. (Yang Yie), Cloutier, M.M. (Michelle M.), Dekker, H.T. (Herman) den, Duijts, L. (Liesbeth), Jongste, J.C. (Johan) de, Dijk, F.N. (F. Nicole), Koppelman, G.H. (Gerard), Flores, C. (Carlos), Hernandez-Pacheco, N. (Natalia), Pino-Yanes, M. (Maria), Mukhopadhyay, S. (Somnath), Basu, K. (Kaninika), Bignell, L. (Lauren), Tantisira, K.G. (Kelan G.), Turner, S.W. (Steve), Verhamme, K.M.C. (Katia), Francis, B. (Ben), Pirmohamed, M. (Munir), Sinha, I. (Ian), and Hawcutt, D.B. (Daniel B.)

Abstract

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

Published
2020
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3. Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Author

Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Yousefi, P. (Paul), Relton, C.L. (Caroline), Merid, S.K. (Simon Kebede), Breton, C. (Carrie), Gao, L. (Lu), Volk, H.E. (Heather E.), Feinberg, J.I. (Jason I.), Ladd-Acosta, C. (Christine), Bakulski, K. (Kelly), Auffray, C. (C.), Lemonnier, N. (Nathanaël), Plusquin, M. (Michelle), Ghantous, A. (Akram), Herceg, Z. (Zdenko), Nawrot, T.S. (Tim S.), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Rusconi, F. (Franca), Vineis, P. (Paolo), Kogevinas, M. (Manolis), Felix, J.F. (Janine), Duijts, L. (Liesbeth), Dekker, H.T. (Herman) den, Jaddoe, V.W.V. (Vincent), Ruiz, J.L. (José L), Bustamante, M. (Mariona), Anto, J.M. (Josep), Sunyer, J. (Jordi), Vrijheid, M. (Martine), Gutzkow, K.B. (Kristine B.), Grazuleviciene, R. (Regina), Hernandez-Ferrer, C. (Carles), Annesi-Maesano, I. (Isabella), Lepeule, J. (Johanna), Bousquet, J. (Jean), Bergström, A. (Anna), Kull, C.A. (Christian), Söderhäll, C. (Cilla), Kere, J. (Juha), Gehring, U. (Ulrike), Brunekreef, B. (Bert), Just, A.C. (Allan C.), Wright, R.J. (Rosalind J.), Peng, C. (Cheng), Gold, D.R. (Diane), Kloog, I. (Itai), Demeo, D.L. (Dawn), Pershagen, G. (Göran), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Baccarelli, A.A. (Andrea), Melén, E. (Erik), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Yousefi, P. (Paul), Relton, C.L. (Caroline), Merid, S.K. (Simon Kebede), Breton, C. (Carrie), Gao, L. (Lu), Volk, H.E. (Heather E.), Feinberg, J.I. (Jason I.), Ladd-Acosta, C. (Christine), Bakulski, K. (Kelly), Auffray, C. (C.), Lemonnier, N. (Nathanaël), Plusquin, M. (Michelle), Ghantous, A. (Akram), Herceg, Z. (Zdenko), Nawrot, T.S. (Tim S.), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Rusconi, F. (Franca), Vineis, P. (Paolo), Kogevinas, M. (Manolis), Felix, J.F. (Janine), Duijts, L. (Liesbeth), Dekker, H.T. (Herman) den, Jaddoe, V.W.V. (Vincent), Ruiz, J.L. (José L), Bustamante, M. (Mariona), Anto, J.M. (Josep), Sunyer, J. (Jordi), Vrijheid, M. (Martine), Gutzkow, K.B. (Kristine B.), Grazuleviciene, R. (Regina), Hernandez-Ferrer, C. (Carles), Annesi-Maesano, I. (Isabella), Lepeule, J. (Johanna), Bousquet, J. (Jean), Bergström, A. (Anna), Kull, C.A. (Christian), Söderhäll, C. (Cilla), Kere, J. (Juha), Gehring, U. (Ulrike), Brunekreef, B. (Bert), Just, A.C. (Allan C.), Wright, R.J. (Rosalind J.), Peng, C. (Cheng), Gold, D.R. (Diane), Kloog, I. (Itai), Demeo, D.L. (Dawn), Pershagen, G. (Göran), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Baccarelli, A.A. (Andrea), and Melén, E. (Erik)

Abstract

BACKGROUND: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. OBJECTIVES: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. RESULTS: Six CpGs were significantly associa

Published
2019
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4. Erratum to: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author

Waage, J. (Johannes), Standl, M. (Marie), Curtin, J.A. (John), Jessen, L.E. (Leon E.), Thorsen, J. (Jonathan), Tian, C. (Chao), Schoettler, N. (Nathan), Flores, C. (Carlos), Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Anto, J.M. (Josep), Barreto-Luis, A. (Amalia), Baurecht, H. (Hansjörg), Beijsterveldt, C.E.M. (Toos) van, Bleecker, E.R. (E.), Bonàs-Guarch, S. (Silvia), Boomsma, D.I. (Dorret), Brix, S. (Susanne), Bunyavanich, S. (Supinda), Burchard, E.G. (Esteban), Chen, Z. (Zhanghua), Curjuric, I. (Ivan), Custovic, A. (Adnan), Dekker, H.T. (Herman) den, Dharmage, S.C. (Shyamali C.), Dmitrieva, J. (Julia), Duijts, L. (Liesbeth), Ege, M. (Markus), Gauderman, W.J. (W James), Georges, M. (Michel), Gieger, C. (Christian), Gilliland, D.G. (Gary), Granell, R. (Raquel), Gui, H. (Hongsheng), Hansen, T. (Torben), Heinrich, J. (Joachim), Henderson, J. (John), Hernandez-Pacheco, N. (Natalia), Holt, P.G. (Patrick), Imboden, M. (Medea), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Jarvis, D.L. (Deborah), Jensen, K.K. (Kamilla K.), Jonsdottir, I. (Ingileif), Kabesch, M. (Michael), Kaprio, J. (Jaakko), Kumar, A. (Ashish), Lee, Y.-A. (Young-Ae), Levin, A.M. (Albert M.), Li, X. (Xingnan), Lorenzo-Diaz, F. (Fabian), Melén, E. (Erik), Mercader, J.M. (Josep M.), Meyers, D.A. (Deborah A.), Myers, R.A. (Rachel A.), Nicolae, D. (Dan), Nohr, C. (Christian), Palviainen, T. (Teemu), Paternoster, L. (Lavinia), Pennell, C.E. (Craig E.), Pershagen, G. (Göran), Pino-Yanes, M. (Maria), Probst-Hensch, N.M. (Nicole M.), Rüschendorf, F. (Franz), Simpson, A. (Angela), Zwart, J-A. (John-Anker), Sunyer, J. (Jordi), Sveinbjornsson, G. (Gardar), Thiering, E. (Elisabeth), Thompson, P.J. (Philip J.), Torrent, M. (Maties), Torrents, D. (David), Tung, J.Y. (Joyce Y.), Wang, C.A. (Carol A.), Weidinger, S. (Stephan), Weiss, S.T. (Scott T.), Willemsen, G.A.H.M. (Gonneke), Williams, L.K. (L. Keoki), Ober, C. (Carole), Hinds, D.A. (David A.), Ferreira, M.A. (Manuel), Bisgaard, H. (Hans), Arnold, A.M. (Alice), Strachan, D.P. (David), Bønnelykke, K. (Klaus), Waage, J. (Johannes), Standl, M. (Marie), Curtin, J.A. (John), Jessen, L.E. (Leon E.), Thorsen, J. (Jonathan), Tian, C. (Chao), Schoettler, N. (Nathan), Flores, C. (Carlos), Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Anto, J.M. (Josep), Barreto-Luis, A. (Amalia), Baurecht, H. (Hansjörg), Beijsterveldt, C.E.M. (Toos) van, Bleecker, E.R. (E.), Bonàs-Guarch, S. (Silvia), Boomsma, D.I. (Dorret), Brix, S. (Susanne), Bunyavanich, S. (Supinda), Burchard, E.G. (Esteban), Chen, Z. (Zhanghua), Curjuric, I. (Ivan), Custovic, A. (Adnan), Dekker, H.T. (Herman) den, Dharmage, S.C. (Shyamali C.), Dmitrieva, J. (Julia), Duijts, L. (Liesbeth), Ege, M. (Markus), Gauderman, W.J. (W James), Georges, M. (Michel), Gieger, C. (Christian), Gilliland, D.G. (Gary), Granell, R. (Raquel), Gui, H. (Hongsheng), Hansen, T. (Torben), Heinrich, J. (Joachim), Henderson, J. (John), Hernandez-Pacheco, N. (Natalia), Holt, P.G. (Patrick), Imboden, M. (Medea), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Jarvis, D.L. (Deborah), Jensen, K.K. (Kamilla K.), Jonsdottir, I. (Ingileif), Kabesch, M. (Michael), Kaprio, J. (Jaakko), Kumar, A. (Ashish), Lee, Y.-A. (Young-Ae), Levin, A.M. (Albert M.), Li, X. (Xingnan), Lorenzo-Diaz, F. (Fabian), Melén, E. (Erik), Mercader, J.M. (Josep M.), Meyers, D.A. (Deborah A.), Myers, R.A. (Rachel A.), Nicolae, D. (Dan), Nohr, C. (Christian), Palviainen, T. (Teemu), Paternoster, L. (Lavinia), Pennell, C.E. (Craig E.), Pershagen, G. (Göran), Pino-Yanes, M. (Maria), Probst-Hensch, N.M. (Nicole M.), Rüschendorf, F. (Franz), Simpson, A. (Angela), Zwart, J-A. (John-Anker), Sunyer, J. (Jordi), Sveinbjornsson, G. (Gardar), Thiering, E. (Elisabeth), Thompson, P.J. (Philip J.), Torrent, M. (Maties), Torrents, D. (David), Tung, J.Y. (Joyce Y.), Wang, C.A. (Carol A.), Weidinger, S. (Stephan), Weiss, S.T. (Scott T.), Willemsen, G.A.H.M. (Gonneke), Williams, L.K. (L. Keoki), Ober, C. (Carole), Hinds, D.A. (David A.), Ferreira, M.A. (Manuel), Bisgaard, H. (Hans), Arnold, A.M. (Alice), Strachan, D.P. (David), and Bønnelykke, K. (Klaus)

Abstract

In the version of this article initially published, in Fig. 3, the _y_-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.

Published
2018
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5. Maternal hemoglobin and hematocrit levels during pregnancy and childhood lung function and asthma. The Generation R Study

Author

Pereira de Jesus, S.M.C.B. (Sabrina M. C. B.), Dekker, H.T. (Herman) den, Jongste, J.C. (Johan) de, Reiss, I.K.M. (Irwin), Steegers, E.A.P. (Eric), Jaddoe, V.W.V. (Vincent), Duijts, L. (Liesbeth), Pereira de Jesus, S.M.C.B. (Sabrina M. C. B.), Dekker, H.T. (Herman) den, Jongste, J.C. (Johan) de, Reiss, I.K.M. (Irwin), Steegers, E.A.P. (Eric), Jaddoe, V.W.V. (Vincent), and Duijts, L. (Liesbeth)

Abstract

Objective: To examine the associations of maternal hemoglobin and hematocrit levels during pregnancy with childhood lung function and asthma, and whether adverse pregnancy outcomes and atopic predisposition modify the associations. Methods: In a population-based prospective cohort study among 3672 subjects, we measured maternal hemoglobin and hematocrit levels in early pregnancy, and lung function by spirometry and current asthma by questionnaire at age 10 years. Results: Higher maternal hematocrit levels, both continuously and categorized into clinical cut-offs, were associated with lower forced expiratory flow at 75% of forced vital capacity (FEF75) in children (Z-score (95%CI): −0.04 (−0.07, −0.01), per increase of 1 SDS in hematocrit level; Z-score (95%CI) difference: −0.11 (−0.20, −0.03) compared with normal hematocrit levels, respectively), taking lifestyle and socio-economic factors into account. Adverse pregnancy outcomes and atopic predisposition did not modify the results. No associations of maternal hemoglobin and hematocrit with current asthma were observed. Conclusion: Higher maternal hematocrit levels during pregnancy are associated with lower childhood lung function but not with risk of asthma. Adverse pregnancy outcomes and atopic predisposition do not modify these associations. Underlying mechanisms need to be further studied.

Published
2018
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6. Early Environmental and Epigenetic Influences on Respiratory Health

Author

Dekker, H.T. (Herman) den and Dekker, H.T. (Herman) den

Abstract

In this thesis, we examined the hypothesis that early growth and adverse environmental exposures in fetal life and infancy, in combination with genetic susceptibility, lead to structural and functional adaptations in early lung development, with subsequently lower lung function and higher risk of chronic obstructive respiratory diseases in later life. Furthermore, we explored epigenetic mechanisms as a potential pathway explaining environmental and genetic factors that influence the development of lower lung function and risk of respiratory diseases. By identification of early life growth and environmental exposures, genetic variants, and DNA-methylation as underlying mechanism, we improve the understanding of the origins of chronic obstructive respiratory diseases in childhood and adulthood. Furthermore, we might be able to develop new preventive strategies and therapeutic interventions for pregnant women and young children, aiming at reducing the burden of later life chronic obstructive respiratory diseases.

Published
2017

7. TRPA1 gene polymorphisms and childhood asthma

Author

Gallo, V. (Valentina), Dijk, F.N. (Nicole), Holloway, J. (John), Ring, S.M. (Susan), Koppelman, G.H. (Gerard), Postma, D.S. (Dirkje), Strachan, D.P. (David), Granell, R. (Raquel), Jongste, J.C. (Johan) de, Jaddoe, V.W.V. (Vincent), Dekker, H.T. (Herman) den, Duijts, L. (Liesbeth), Henderson, A.J. (A. John), Shaheen, S.O. (Seif O.), Gallo, V. (Valentina), Dijk, F.N. (Nicole), Holloway, J. (John), Ring, S.M. (Susan), Koppelman, G.H. (Gerard), Postma, D.S. (Dirkje), Strachan, D.P. (David), Granell, R. (Raquel), Jongste, J.C. (Johan) de, Jaddoe, V.W.V. (Vincent), Dekker, H.T. (Herman) den, Duijts, L. (Liesbeth), Henderson, A.J. (A. John), and Shaheen, S.O. (Seif O.)

Abstract

Background: Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. Methods: We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We sought to confirm the most significant associations with comparable outcomes in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) and Generation R birth cohorts. In ALSPAC, we explored interactions with prenatal paracetamol exposure. Results: In ALSPAC, there was strong evidence for association between six SNPs and asthma: rs959974 and rs1384001 (per-allele odds ratio for both: 1.30 (95% CI: 1.15-1.47), p = 0.00001), rs7010969 (OR 1.28 (1.13-1.46), p = 0.00004), rs3735945 (OR 1.30 (1.09-1.55), p = 0.003), rs920829 (OR 1.30 (1.09-1.54), p = 0.004) and rs4738202 (OR 1.22 (1.07-1.39), p = 0.004). In a meta-analysis across the three cohorts, the pooled effect estimates confirmed that all six SNPs were significantly associated with asthma. In ALSPAC, TRPA1 associations with asthma were not modified by prenatal paracetamol, although associations with IgE concentration were. Conclusion: This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words).

Published
2017
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8. Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Author

Joubert, B.R. (Bonnie), Dekker, H.T. (Herman) den, Felix, J.F. (Janine), Bohlin, J. (Jon), Ligthart, S. (Symen), Beckett, E. (Emma), Tiemeier, H.W. (Henning), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Hofman, A. (Albert), Håberg, S.E. (Siri E), Reese, S.E. (Sarah E.), Peters, M.J. (Marjolein), Kulle Andreassen, B. (Bettina), Steegers, E.A.P. (Eric), Nilsen, R.M. (Roy M.), Vollset, S.E. (Stein E.), Midttun, . (Øivind), Ueland, P.M. (Per), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Jongste, J.C. (Johan) de, Wu, M.C. (Michael), Wang, T. (Tianyuan), Peddada, S.D. (Shyamal D.), Jaddoe, V.W.V. (Vincent), Nystad, W. (Wenche), Duijts, L. (Liesbeth), London, S.J. (Stephanie J), Joubert, B.R. (Bonnie), Dekker, H.T. (Herman) den, Felix, J.F. (Janine), Bohlin, J. (Jon), Ligthart, S. (Symen), Beckett, E. (Emma), Tiemeier, H.W. (Henning), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Hofman, A. (Albert), Håberg, S.E. (Siri E), Reese, S.E. (Sarah E.), Peters, M.J. (Marjolein), Kulle Andreassen, B. (Bettina), Steegers, E.A.P. (Eric), Nilsen, R.M. (Roy M.), Vollset, S.E. (Stein E.), Midttun, . (Øivind), Ueland, P.M. (Per), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Jongste, J.C. (Johan) de, Wu, M.C. (Michael), Wang, T. (Tianyuan), Peddada, S.D. (Shyamal D.), Jaddoe, V.W.V. (Vincent), Nystad, W. (Wenche), Duijts, L. (Liesbeth), and London, S.J. (Stephanie J)

Abstract

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina" s HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring.

Published
2016
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