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1. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Author

Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Melén, E. (Erik), Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), and Melén, E. (Erik)

Abstract

BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

Published
2020
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2. 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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3. Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Author

Reese, S. E. (Sarah E.), Xu, C.-J. (Cheng-Jian), den Dekker, H. T. (Herman T.), Lee, M. K. (Mi Kyeong), Sikdar, S. (Sinjini), Ruiz-Arenas, C. (Carlos), Merid, S. K. (Simon K.), Rezwan, F. I. (Faisal I.), Page, C. M. (Christian M.), Ullemar, V. (Vilhelmina), Melton, P. E. (Phillip E.), Oh, S. S. (Sam S.), Yang, I. V. (Ivana V.), Burrows, K. (Kimberley), Söderhäll, C. (Cilla), Jima, D. D. (Dereje D.), Gao, L. (Lu), Arathimos, R. (Ryan), Küpers, L. K. (Leanne K.), Wielscher, M. (Matthias), Rzehak, P. (Peter), Lahti, J. (Jari), Laprise, C. (Catherine), Madore, A.-M. (Anne-Marie), Ward, J. (James), Bennett, B. D. (Brian D.), Wang, T. (Tianyuan), Bell, D. A. (Douglas A.), T. B. (The BIOS consortium), Vonk, J. M. (Judith M.), Håberg, S. E. (Siri E.), Zhao, S. (Shanshan), Karlsson, R. (Robert), Hollams, E. (Elysia), Hu, D. (Donglei), Richards, A. J. (Adam J.), Bergström, A. (Anna), Sharp, G. C. (Gemma C.), Felix, J. F. (Janine F.), Bustamante, M. (Mariona), Gruzieva, O. (Olena), Maguire, R. L. (Rachel L.), Gilliland, F. (Frank), Baïz, N. (Nour), Nohr, E. A. (Ellen A.), Corpeleijn, E. (Eva), Sebert, S. (Sylvain), Karmaus, W. (Wilfried), Grote, V. (Veit), Kajantie, E. (Eero), Magnus, M. C. (Maria C.), Örtqvist, A. K. (Anne K.), Eng, C. (Celeste), Liu, A. H. (Andrew H.), Kull, I. (Inger), Jaddoe, V. W. (Vincent W.V.), Sunyer, J. (Jordi), Kere, J. (Juha), Hoyo, C. (Cathrine), Annesi-Maesano, I. (Isabella), Arshad, S. H. (Syed Hasan), Koletzko, B. (Berthold), Brunekreef, B. (Bert), Binder, E. B. (Elisabeth B.), Räikkönen, K. (Katri), Reischl, E. (Eva), Holloway, J. W. (John W.), Järvelin, M.-R. (Marjo-Riitta), Snieder, H. (Harold), Kazmi, N. (Nabila), Breton, C. V. (Carrie V.), Murphy, S. K. (Susan K.), Pershagen, G. (Göran), Anto, J. M. (Josep Maria), Relton, C. L. (Caroline L.), Schwartz, D. A. (David A.), Burchard, E. G. (Esteban G.), Huang, R.-C. (Rae-Chi), Nystad, W. (Wenche), Almqvist, C. (Catarina), Henderson, A. J. (A. John), Melén, E. (Erik), Duijts, L. (Liesbeth), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Reese, S. E. (Sarah E.), Xu, C.-J. (Cheng-Jian), den Dekker, H. T. (Herman T.), Lee, M. K. (Mi Kyeong), Sikdar, S. (Sinjini), Ruiz-Arenas, C. (Carlos), Merid, S. K. (Simon K.), Rezwan, F. I. (Faisal I.), Page, C. M. (Christian M.), Ullemar, V. (Vilhelmina), Melton, P. E. (Phillip E.), Oh, S. S. (Sam S.), Yang, I. V. (Ivana V.), Burrows, K. (Kimberley), Söderhäll, C. (Cilla), Jima, D. D. (Dereje D.), Gao, L. (Lu), Arathimos, R. (Ryan), Küpers, L. K. (Leanne K.), Wielscher, M. (Matthias), Rzehak, P. (Peter), Lahti, J. (Jari), Laprise, C. (Catherine), Madore, A.-M. (Anne-Marie), Ward, J. (James), Bennett, B. D. (Brian D.), Wang, T. (Tianyuan), Bell, D. A. (Douglas A.), T. B. (The BIOS consortium), Vonk, J. M. (Judith M.), Håberg, S. E. (Siri E.), Zhao, S. (Shanshan), Karlsson, R. (Robert), Hollams, E. (Elysia), Hu, D. (Donglei), Richards, A. J. (Adam J.), Bergström, A. (Anna), Sharp, G. C. (Gemma C.), Felix, J. F. (Janine F.), Bustamante, M. (Mariona), Gruzieva, O. (Olena), Maguire, R. L. (Rachel L.), Gilliland, F. (Frank), Baïz, N. (Nour), Nohr, E. A. (Ellen A.), Corpeleijn, E. (Eva), Sebert, S. (Sylvain), Karmaus, W. (Wilfried), Grote, V. (Veit), Kajantie, E. (Eero), Magnus, M. C. (Maria C.), Örtqvist, A. K. (Anne K.), Eng, C. (Celeste), Liu, A. H. (Andrew H.), Kull, I. (Inger), Jaddoe, V. W. (Vincent W.V.), Sunyer, J. (Jordi), Kere, J. (Juha), Hoyo, C. (Cathrine), Annesi-Maesano, I. (Isabella), Arshad, S. H. (Syed Hasan), Koletzko, B. (Berthold), Brunekreef, B. (Bert), Binder, E. B. (Elisabeth B.), Räikkönen, K. (Katri), Reischl, E. (Eva), Holloway, J. W. (John W.), Järvelin, M.-R. (Marjo-Riitta), Snieder, H. (Harold), Kazmi, N. (Nabila), Breton, C. V. (Carrie V.), Murphy, S. K. (Susan K.), Pershagen, G. (Göran), Anto, J. M. (Josep Maria), Relton, C. L. (Caroline L.), Schwartz, D. A. (David A.), Burchard, E. G. (Esteban G.), Huang, R.-C. (Rae-Chi), Nystad, W. (Wenche), Almqvist, C. (Catarina), Henderson, A. J. (A. John), Melén, E. (Erik), Duijts, L. (Liesbeth), Koppelman, G. H. (Gerard H.), and London, S. J. (Stephanie J.)

Abstract

Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

Published
2019

4. 17q21 variant increases the risk of exacerbations in asthmatic children despite inhaled corticosteroids use

Author

Farzan, Niloufar, Vijverberg, S.J.H. (Susanne), Hernandez-Pacheco, N., Bel, E.H., Berce, Vojko, Bønnelykke, K., Bisgaard, H. (Hans), Burchard, E.G. (Esteban), Canino, G., Celedón, Juan Carlos, Chew, Fook Tim, Chiang, W.C., Cloutier, M.M., Forno, Erick, Francis, Ben, Hawcutt, Daniel B., Herrera-Luis, E., Kabesch, M. (Michael), Karimi, L. (Leila), Melén, E., Mukhopadhyay, S., Merid, S.K. (Simon Kebede), Palmer, C.N.A. (Colin), Pino-Yanes, Maria, Pirmohamed, M. (Munir), Potočnik, Uros, Repnik, Katja, Schieck, Maximilian, Sevelsted, A. (Astrid), Sio, Y.Y., Smyth, Rosalind L., Soares, Patricia, Söderhäll, C. (Cilla), Tantisira, K.G., Tavendale, R. (Roger), Tse, Sze Man, Turner, S.W. (Steve), Verhamme, K.M.C. (Katia), Maitland-van der Zee, A-H. (Anke-Hilse), Farzan, Niloufar, Vijverberg, S.J.H. (Susanne), Hernandez-Pacheco, N., Bel, E.H., Berce, Vojko, Bønnelykke, K., Bisgaard, H. (Hans), Burchard, E.G. (Esteban), Canino, G., Celedón, Juan Carlos, Chew, Fook Tim, Chiang, W.C., Cloutier, M.M., Forno, Erick, Francis, Ben, Hawcutt, Daniel B., Herrera-Luis, E., Kabesch, M. (Michael), Karimi, L. (Leila), Melén, E., Mukhopadhyay, S., Merid, S.K. (Simon Kebede), Palmer, C.N.A. (Colin), Pino-Yanes, Maria, Pirmohamed, M. (Munir), Potočnik, Uros, Repnik, Katja, Schieck, Maximilian, Sevelsted, A. (Astrid), Sio, Y.Y., Smyth, Rosalind L., Soares, Patricia, Söderhäll, C. (Cilla), Tantisira, K.G., Tavendale, R. (Roger), Tse, Sze Man, Turner, S.W. (Steve), Verhamme, K.M.C. (Katia), and Maitland-van der Zee, A-H. (Anke-Hilse)

Abstract

_To the Editor,_ Approximately 25% of the asthmatic children suffer from uncontrolled asthma despite regular use of inhaled corticosteroids (ICS). Variation within the 17q21 locus is the strongest genetic determinant for childhood‐onset asthma. Recently, the influence of this locus on treatment outcomes has been shown in several studies. The Pharmacogenomics in Childhood Asthma (PiCA) consortium is a multiethnic consortium that brings together data from ≥14 000 asthmatic children/young adults from 12 different countries to study the pharmacogenomics of uncontrolled asthma despite treatment. In 14 PiCA populations (with over 4000 asthmatic patients), we studied the association between variation in the 17q21 locus, and asthma exacerbations despite ICS use. We specifically focused on rs7216389, a single nucleotide polymorphism (SNP) in the 17q21 locus strongly associated with childhood asthma and initially identified by Moffatt et al. [...]

Published
2018
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5. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

Joubert, B.R. (Bonnie), Felix, J.F. (Janine), Yousefi, P. (Paul), Bakulski, K.M. (Kelly M.), Just, A.C. (Allan C.), Breton, C. (Carrie), Reese, S.E. (Sarah E.), Markunas, C.A. (Christina A.), Richmond, R.C. (Rebecca C.), Xu, C.-J. (Cheng-Jian), Küpers, L.K. (Leanne), Oh, S.S. (Sam S.), Hoyo, C. (Cathrine), Gruzieva, O. (Olena), Söderhäll, C. (Cilla), Salas, L.A. (Lucas A.), Baïz, N. (Nour), Zhang, H. (Hongmei), Lepeule, J. (Johanna), Ruiz, C. (Carlos), Ligthart, S. (Symen), Wang, T. (Tianyuan), Taylor, J.A. (Jack A.), Duijts, L. (Liesbeth), Sharp, G.C. (Gemma C.), Jankipersadsing, S.A. (Soesma A.), Nilsen, R.M. (Roy M.), Vaez, A. (Ahmad), Fallin, M.D. (M. Daniele), Hu, D. (Donglei), Litonjua, A.A. (Augusto), Fuemmeler, B.F. (Bernard F.), Huen, K. (Karen), Kere, J. (Juha), Kull, C.A. (Christian), Munthe-Kaas, M.C. (Monica Cheng), Gehring, U. (Ulrike), Bustamante, M. (Mariona), Saurel-Coubizolles, M.J. (Marie José), Quraishi, B.M. (Bilal M.), Ren, J. (Jie), Tost, J. (Jörg), Gonzalez, J.R. (Juan R.), Peters, M.J. (Marjolein), Håberg, S.E. (Siri E), Xu, Z. (Zongli), Meurs, J.B.J. (Joyce) van, Gaunt, T.R. (Tom), Kerkhof, M. (Marjan), Corpeleijn, W.E. (Willemijn), Feinberg, A.P. (Andrew P.), Eng, C. (Celeste), Baccarelli, A.A. (Andrea), Benjamin Neelon, S.E. (Sara E.), Bradman, A. (Asa), Merid, S.K. (Simon Kebede), Bergström, A. (Anna), Herceg, Z. (Zdenko), Hernandez-Vargas, H. (Hector), Brunekreef, B. (Bert), Pinart, M. (Mariona), Heude, B. (Barbara), Ewart, S. (Susan), Yao, J. (Jin), Lemonnier, N. (Nathanaël), Franco, O.H. (Oscar), Wu, M.C. (Michael), Hofman, A. (Albert), McArdle, W.L. (Wendy), Vlies, P. (P.) van der, Falahi, F. (Fahimeh), Gillman, M.W. (Matthew W.), Barcellos, L.F. (Lisa), Kumar, A. (Ashish), Wickman, M. (Magnus), Guerra, S. (S.), Charles, M.-A. (Marie-Aline), Holloway, J. (John), Auffray, C. (C.), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), Postma, D.S. (Dirkje), Hivert, M.-F. (Marie-France), Eskenazi, B. (Brenda), Vrijheid, M. (Martine), Arshad, H. (Hasan), Anto, J.M. (Josep), Dehghan, A. (Abbas), Karmaus, W. (Wilfried), Annesi-Maesano, I. (Isabella), Sunyer, J. (Jordi), Ghantous, A. (Akram), Pershagen, G. (Göran), Holland, N. (Nina), Murphy, S.K. (Susan K.), Demeo, D.L. (Dawn), Burchard, E.G. (Esteban), Ladd-Acosta, C. (Christine), Snieder, H. (Harold), Nystad, W. (Wenche), Koppelman, G.H. (Gerard), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), Wilcox, A.J. (Allen), Melén, E. (Erik), London, S.J. (Stephanie J.), Joubert, B.R. (Bonnie), Felix, J.F. (Janine), Yousefi, P. (Paul), Bakulski, K.M. (Kelly M.), Just, A.C. (Allan C.), Breton, C. (Carrie), Reese, S.E. (Sarah E.), Markunas, C.A. (Christina A.), Richmond, R.C. (Rebecca C.), Xu, C.-J. (Cheng-Jian), Küpers, L.K. (Leanne), Oh, S.S. (Sam S.), Hoyo, C. (Cathrine), Gruzieva, O. (Olena), Söderhäll, C. (Cilla), Salas, L.A. (Lucas A.), Baïz, N. (Nour), Zhang, H. (Hongmei), Lepeule, J. (Johanna), Ruiz, C. (Carlos), Ligthart, S. (Symen), Wang, T. (Tianyuan), Taylor, J.A. (Jack A.), Duijts, L. (Liesbeth), Sharp, G.C. (Gemma C.), Jankipersadsing, S.A. (Soesma A.), Nilsen, R.M. (Roy M.), Vaez, A. (Ahmad), Fallin, M.D. (M. Daniele), Hu, D. (Donglei), Litonjua, A.A. (Augusto), Fuemmeler, B.F. (Bernard F.), Huen, K. (Karen), Kere, J. (Juha), Kull, C.A. (Christian), Munthe-Kaas, M.C. (Monica Cheng), Gehring, U. (Ulrike), Bustamante, M. (Mariona), Saurel-Coubizolles, M.J. (Marie José), Quraishi, B.M. (Bilal M.), Ren, J. (Jie), Tost, J. (Jörg), Gonzalez, J.R. (Juan R.), Peters, M.J. (Marjolein), Håberg, S.E. (Siri E), Xu, Z. (Zongli), Meurs, J.B.J. (Joyce) van, Gaunt, T.R. (Tom), Kerkhof, M. (Marjan), Corpeleijn, W.E. (Willemijn), Feinberg, A.P. (Andrew P.), Eng, C. (Celeste), Baccarelli, A.A. (Andrea), Benjamin Neelon, S.E. (Sara E.), Bradman, A. (Asa), Merid, S.K. (Simon Kebede), Bergström, A. (Anna), Herceg, Z. (Zdenko), Hernandez-Vargas, H. (Hector), Brunekreef, B. (Bert), Pinart, M. (Mariona), Heude, B. (Barbara), Ewart, S. (Susan), Yao, J. (Jin), Lemonnier, N. (Nathanaël), Franco, O.H. (Oscar), Wu, M.C. (Michael), Hofman, A. (Albert), McArdle, W.L. (Wendy), Vlies, P. (P.) van der, Falahi, F. (Fahimeh), Gillman, M.W. (Matthew W.), Barcellos, L.F. (Lisa), Kumar, A. (Ashish), Wickman, M. (Magnus), Guerra, S. (S.), Charles, M.-A. (Marie-Aline), Holloway, J. (John), Auffray, C. (C.), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), Postma, D.S. (Dirkje), Hivert, M.-F. (Marie-France), Eskenazi, B. (Brenda), Vrijheid, M. (Martine), Arshad, H. (Hasan), Anto, J.M. (Josep), Dehghan, A. (Abbas), Karmaus, W. (Wilfried), Annesi-Maesano, I. (Isabella), Sunyer, J. (Jordi), Ghantous, A. (Akram), Pershagen, G. (Göran), Holland, N. (Nina), Murphy, S.K. (Susan K.), Demeo, D.L. (Dawn), Burchard, E.G. (Esteban), Ladd-Acosta, C. (Christine), Snieder, H. (Harold), Nystad, W. (Wenche), Koppelman, G.H. (Gerard), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), Wilcox, A.J. (Allen), Melén, E. (Erik), and London, S.J. (Stephanie J.)

Abstract

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathwa

Published
2016
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6. Meta-analysis identifies seven susceptibility loci involved in the atopic March

Author

Marenholz, I. (Ingo), Esparza-Gordillo, J. (Jorge), Rüschendorf, F. (Franz), Bauerfeind, A. (Anja), Strachan, D.P. (David P.), Spycher, B.D. (Ben D.), Baurecht, H. (Hansjörg), Margaritte-Jeannin, P. (Patricia), Sääf, A. (Annika), Kerkhof, M. (Marjan), Ege, M. (Markus), Baltic, S. (Svetlana), Matheson, J., Li, J. (Jin), Michel, S. (Sven), Ang, W.Q. (Wei Q.), McArdle, W.L. (Wendy), Homuth, G. (Georg), Demenais, F. (Florence), Bouzigon, E. (Emmanuelle), Söderhäll, C. (Cilla), Pershagen, G. (Göran), Jongste, J.C. (Johan) de, Postma, D.S. (Dirkje), Braun-Fahrländer, C. (Charlotte), Horak, E. (Elisabeth), Ogorodova, L.M. (Ludmila M.), Puzyrev, V.P. (Valery P.), Bragina, E.Y. (Elena Yu), Hudson, T.J. (Thomas), Morin, C. (Charles), Duffy, D.L. (David), Marks, G.B. (Guy B.), Robertson, C., Montgomery, G.W. (Grant), Musk, A.W. (Arthur), Thompson, P.J. (Philip), Martin, N.G. (Nicholas), James, A.L. (Alan), Sleiman, P.M.A. (Patrick), Toskala, E. (Elina), Rodríguez, P.M., Fölster-Holst, R. (R.), Franke, A. (Andre), Lieb, W. (Wolfgang), Gieger, C. (Christian), Heinzmann, A. (Andrea), Rietschel, E. (Ernst), Keil, M. (Mark), Cichon, S. (Sven), Nöthen, M.M. (Markus M.), Pennell, C.E. (Craig), Sly, P.D., Schmidt, C.O. (Carsten Oliver), Matanovic, A. (Anja), Schneider, V. (Valentin), Heinig, M. (Matthias), Hübner, N. (Norbert), Holt, P.G. (Patrick), Lau, S. (Susanne), Kabesch, M. (Michael), Weidinger, S. (Stefan), Hakonarson, H. (Hakon), Ferreira, M.A. (Manuel), Laprise, C. (Catherine), Freidin, M.B. (M.), Genuneit, J. (Jon), Koppelman, G.H. (Gerard), Melén, E. (Erik), Dizier, M.-H., Arnold, A.M. (Alice), Henderson, A.J. (A. John), Lee, Y.-A. (Young-Ae), Marenholz, I. (Ingo), Esparza-Gordillo, J. (Jorge), Rüschendorf, F. (Franz), Bauerfeind, A. (Anja), Strachan, D.P. (David P.), Spycher, B.D. (Ben D.), Baurecht, H. (Hansjörg), Margaritte-Jeannin, P. (Patricia), Sääf, A. (Annika), Kerkhof, M. (Marjan), Ege, M. (Markus), Baltic, S. (Svetlana), Matheson, J., Li, J. (Jin), Michel, S. (Sven), Ang, W.Q. (Wei Q.), McArdle, W.L. (Wendy), Homuth, G. (Georg), Demenais, F. (Florence), Bouzigon, E. (Emmanuelle), Söderhäll, C. (Cilla), Pershagen, G. (Göran), Jongste, J.C. (Johan) de, Postma, D.S. (Dirkje), Braun-Fahrländer, C. (Charlotte), Horak, E. (Elisabeth), Ogorodova, L.M. (Ludmila M.), Puzyrev, V.P. (Valery P.), Bragina, E.Y. (Elena Yu), Hudson, T.J. (Thomas), Morin, C. (Charles), Duffy, D.L. (David), Marks, G.B. (Guy B.), Robertson, C., Montgomery, G.W. (Grant), Musk, A.W. (Arthur), Thompson, P.J. (Philip), Martin, N.G. (Nicholas), James, A.L. (Alan), Sleiman, P.M.A. (Patrick), Toskala, E. (Elina), Rodríguez, P.M., Fölster-Holst, R. (R.), Franke, A. (Andre), Lieb, W. (Wolfgang), Gieger, C. (Christian), Heinzmann, A. (Andrea), Rietschel, E. (Ernst), Keil, M. (Mark), Cichon, S. (Sven), Nöthen, M.M. (Markus M.), Pennell, C.E. (Craig), Sly, P.D., Schmidt, C.O. (Carsten Oliver), Matanovic, A. (Anja), Schneider, V. (Valentin), Heinig, M. (Matthias), Hübner, N. (Norbert), Holt, P.G. (Patrick), Lau, S. (Susanne), Kabesch, M. (Michael), Weidinger, S. (Stefan), Hakonarson, H. (Hakon), Ferreira, M.A. (Manuel), Laprise, C. (Catherine), Freidin, M.B. (M.), Genuneit, J. (Jon), Koppelman, G.H. (Gerard), Melén, E. (Erik), Dizier, M.-H., Arnold, A.M. (Alice), Henderson, A.J. (A. John), and Lee, Y.-A. (Young-Ae)

Abstract

Eczema often precedes the development of asthma in a disease course called the a 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified a

Published
2015
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7. Associations between the 17q21 region and allergic rhinitis in 5 birth cohorts

Author

Fuertes, E. (Elaine), Söderhäll, C. (Cilla), Acevedo, N. (Nathalie), Becker, A. (Albert), Brauer, M., Chan Yeung, M. (Moira), Dijk, F.N. (Nicole), Heinrich, J. (Joachim), Jongste, J.C. (Johan) de, Koppelman, G.H. (Gerard), Postma, D.S. (Dirkje), Kere, J. (Juha), Kozyrskyj, A. (Anita), Pershagen, G. (Göran), Sandford, A. (Andrew), Standl, E. (Eberhard), Tiesler, C. (Carla), Waldenberger, M. (Melanie), Westman, M. (Marit), Carlsten, C. (Christopher), Melén, E. (Erik), Fuertes, E. (Elaine), Söderhäll, C. (Cilla), Acevedo, N. (Nathalie), Becker, A. (Albert), Brauer, M., Chan Yeung, M. (Moira), Dijk, F.N. (Nicole), Heinrich, J. (Joachim), Jongste, J.C. (Johan) de, Koppelman, G.H. (Gerard), Postma, D.S. (Dirkje), Kere, J. (Juha), Kozyrskyj, A. (Anita), Pershagen, G. (Göran), Sandford, A. (Andrew), Standl, E. (Eberhard), Tiesler, C. (Carla), Waldenberger, M. (Melanie), Westman, M. (Marit), Carlsten, C. (Christopher), and Melén, E. (Erik)

Published
2015
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