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142 results on '"Plusquin, M."'

1. Pooled analysis of genotoxicity markers in relation to exposure in the Flemish Environment and Health Studies (FLEHS) between 1999 and 2018

Author: Koppen, G., Franken, C., Den Hond, E., Plusquin, M., Reimann, B., Leermakers, M., Covaci, A., Nawrot, T., Van Larebeke, N., Schoeters, G., Bruckers, L., and Govarts, E.
Published: 2020
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2. A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Author: Li, S., Spitz, N., Ghantous, A., Abrishamcar, S., Reimann, B., Marques, I., Silver, M.J., Aguilar-Lacasaña, S., Kitaba, N., Rezwan, F.I., Röder, Stefan, Sirignano, L., Tuhkanen, J., Mancano, G., Sharp, G.C., Metayer, C., Morimoto, L., Stein, D.J., Zar, H.J., Alfano, R., Nawrot, T., Wang, C., Kajantie, E., Keikkala, E., Mustaniemi, S., Ronkainen, J., Sebert, S., Silva, W., Vääräsmäki, M., Jaddoe, V.W.V., Bernstein, R.M., Prentice, A.M., Cosin-Tomas, M., Dwyer, T., Håberg, S.E., Herceg, Z., Magnus, M.C., Munthe-Kaas, M.C., Page, C.M., Völker, M., Gilles, M., Send, T., Witt, S., Zillich, L., Gagliardi, L., Richiardi, L., Czamara, D., Räikkönen, K., Chatzi, L., Vafeiadi, M., Arshad, S.H., Ewart, S, Plusquin, M., Felix, J.F., Moore, S.E., Vrijheid, M., Holloway, J.W., Karmaus, W., Herberth, Gunda, Zenclussen, Ana Claudia, Streit, F., Lahti, J., Hüls, A., Hoang, T.T., London, S.J., Wiemels, J.L., Li, S., Spitz, N., Ghantous, A., Abrishamcar, S., Reimann, B., Marques, I., Silver, M.J., Aguilar-Lacasaña, S., Kitaba, N., Rezwan, F.I., Röder, Stefan, Sirignano, L., Tuhkanen, J., Mancano, G., Sharp, G.C., Metayer, C., Morimoto, L., Stein, D.J., Zar, H.J., Alfano, R., Nawrot, T., Wang, C., Kajantie, E., Keikkala, E., Mustaniemi, S., Ronkainen, J., Sebert, S., Silva, W., Vääräsmäki, M., Jaddoe, V.W.V., Bernstein, R.M., Prentice, A.M., Cosin-Tomas, M., Dwyer, T., Håberg, S.E., Herceg, Z., Magnus, M.C., Munthe-Kaas, M.C., Page, C.M., Völker, M., Gilles, M., Send, T., Witt, S., Zillich, L., Gagliardi, L., Richiardi, L., Czamara, D., Räikkönen, K., Chatzi, L., Vafeiadi, M., Arshad, S.H., Ewart, S, Plusquin, M., Felix, J.F., Moore, S.E., Vrijheid, M., Holloway, J.W., Karmaus, W., Herberth, Gunda, Zenclussen, Ana Claudia, Streit, F., Lahti, J., Hüls, A., Hoang, T.T., London, S.J., and Wiemels, J.L.
Abstract: Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.
Published: 2024

3. Prenatal particulate matter exposure is linked with neurobehavioral development in early life

Author: Cosemans, C, primary, Sleurs, H, additional, Madhloum, N, additional, Alfano, R, additional, Verheyen, L, additional, Vanbrabant, K, additional, Nawrot, T S, additional, and Plusquin, M, additional
Published: 2023
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4. Air pollution-induced placental alterations: an interplay of oxidative stress, epigenetics, and the aging phenotype?

Author: Saenen, N. D., Martens, D. S., Neven, K. Y., Alfano, R., Bové, H., Janssen, B. G., Roels, H. A., Plusquin, M., Vrijens, K., and Nawrot, T. S.
Published: 2019
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5. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence

Author: Choudhary, P., Monasso, G.S., Karhunen, V., Ronkainen, J., Mancano, G., Howe, C.G., Niu, Z., Zeng, X., Guan, W., Dou, J., Feinberg, J.I., Mordaunt, C., Pesce, G., Baïz, N., Alfano, R., Martens, D.S., Wang, C., Isaevska, E., Keikkala, E., Mustaniemi, S., Thio, C.H.L., Fraszczyk, E., Tobi, E.W., Starling, A.P., Cosin-Tomas, M., Urquiza, J., Röder, Stefan, Hoang, T.T., Page, C., Jima, D.D., House, J.S., Maguire, R.L., Ott, R., Pawlow, X., Sirignano, L., Zillich, L., Malmberg, A., Rauschert, S., Melton, P., Gong, T., Karlsson, R., Fore, R., Perng, W., Laubach, Z.M., Czamara, D., Sharp, G., Breton, C.V., Schisterman, E., Yeung, E., Mumford, S.L., Fallin, M.D., LaSalle, J.M., Schmidt, R.J., Bakulski, K.M., Annesi-Maesano, I., Heude, B., Nawrot, T.S., Plusquin, M., Ghantous, A., Herceg, Z., Nisticò, L., Vafeiadi, M., Kogevinas, M., Vääräsmäki, M., Kajantie, E., Snieder, H., Corpeleijn, E., Steegers-Theunissen, R.P.M., Yang, I.V., Dabelea, D., Fossati, S., Zenclussen, Ana Claudia, Herberth, Gunda, Magnus, M., Håberg, S.E., London, S.J., Munthe-Kaas, M.C., Murphy, S.K., Hoyo, C., Ziegler, A.-G., Hummel, S., Witt, S.H., Streit, F., Frank, J., Räikkönen, K., Lahti, J., Huang, R.-C., Almqvist, C., Hivert, M.-F., Jaddoe, V.W.V., Järvelin, M.-R., Kantomaa, M., Felix, J.F., Sebert, S., Choudhary, P., Monasso, G.S., Karhunen, V., Ronkainen, J., Mancano, G., Howe, C.G., Niu, Z., Zeng, X., Guan, W., Dou, J., Feinberg, J.I., Mordaunt, C., Pesce, G., Baïz, N., Alfano, R., Martens, D.S., Wang, C., Isaevska, E., Keikkala, E., Mustaniemi, S., Thio, C.H.L., Fraszczyk, E., Tobi, E.W., Starling, A.P., Cosin-Tomas, M., Urquiza, J., Röder, Stefan, Hoang, T.T., Page, C., Jima, D.D., House, J.S., Maguire, R.L., Ott, R., Pawlow, X., Sirignano, L., Zillich, L., Malmberg, A., Rauschert, S., Melton, P., Gong, T., Karlsson, R., Fore, R., Perng, W., Laubach, Z.M., Czamara, D., Sharp, G., Breton, C.V., Schisterman, E., Yeung, E., Mumford, S.L., Fallin, M.D., LaSalle, J.M., Schmidt, R.J., Bakulski, K.M., Annesi-Maesano, I., Heude, B., Nawrot, T.S., Plusquin, M., Ghantous, A., Herceg, Z., Nisticò, L., Vafeiadi, M., Kogevinas, M., Vääräsmäki, M., Kajantie, E., Snieder, H., Corpeleijn, E., Steegers-Theunissen, R.P.M., Yang, I.V., Dabelea, D., Fossati, S., Zenclussen, Ana Claudia, Herberth, Gunda, Magnus, M., Håberg, S.E., London, S.J., Munthe-Kaas, M.C., Murphy, S.K., Hoyo, C., Ziegler, A.-G., Hummel, S., Witt, S.H., Streit, F., Frank, J., Räikkönen, K., Lahti, J., Huang, R.-C., Almqvist, C., Hivert, M.-F., Jaddoe, V.W.V., Järvelin, M.-R., Kantomaa, M., Felix, J.F., and Sebert, S.
Abstract: Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.
Published: 2023

6. Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

Author: Kadalayil, L., Alam, M., White, C.H., Ghantous, A., Walton, E., Gruzieva, O., Merid, S.K., Kumar, A., Roy, R., Solomon, O., Huen, K., Eskenazi, B., Rzehak, P., Grote, V., Langhendries, J.-P., Verduci, E., Ferre, N., Gruszfeld, D., Gao, L., Guan, W., Zeng, X., Schisterman, E.F., Dou, J., Bakulski, K.M., Feinberg, J.I., Soomro, M.H., Pesce, G., Baiz, N., Isaevska, E., Plusquin, M., Vafeiadi, M., Roumeliotaki, T., Langie, S.A.S., Standaert, A., Allard, C., Perron, P., Bouchard, L., van Meel, E.R., Felix, J.F., Jaddoe, V.W.V., Yousefi, P.D., Ramlau‑Hansen, C.H., Relton, C.L., Tobi, E.W., Starling, A.P., Yang, I.V., Llambrich, M., Santorelli, G., Lepeule, J., Salas, L.A., Bustamante, M., Ewart, S.L., Zhang, H., Karmaus, W., Röder, Stefan, Zenclussen, Ana Claudia, Jin, J., Nystad, W., Page, C.M., Magnus, M., Jima, D.D., Hoyo, C., Maguire, R.L., Kvist, T., Czamara, D., Räikkönen, K., Gong, T., Ullemar, V., Rifas‐Shiman, S.L., Oken, E., Almqvist, C., Karlsson, R., Lahti, J., Murphy, S.K., Håberg, S.E., London, S., Herberth, Gunda, Arshad, H., Sunyer, J., Grazuleviciene, R., Dabelea, D., Steegers‑Theunissen, R.P.M., Nohr, E.A., Sørensen, T.I.A., Duijts, L., Hivert, M.-F., Nelen, V., Popovic, M., Kogevinas, M., Nawrot, T.S., Herceg, Z., Annesi-Maesano, I., Fallin, M.D., Yeung, E., Breton, C.V., Koletzko, B., Holland, N., Melén, E., Sharp, G.C., Silver, M.J., Kadalayil, L., Alam, M., White, C.H., Ghantous, A., Walton, E., Gruzieva, O., Merid, S.K., Kumar, A., Roy, R., Solomon, O., Huen, K., Eskenazi, B., Rzehak, P., Grote, V., Langhendries, J.-P., Verduci, E., Ferre, N., Gruszfeld, D., Gao, L., Guan, W., Zeng, X., Schisterman, E.F., Dou, J., Bakulski, K.M., Feinberg, J.I., Soomro, M.H., Pesce, G., Baiz, N., Isaevska, E., Plusquin, M., Vafeiadi, M., Roumeliotaki, T., Langie, S.A.S., Standaert, A., Allard, C., Perron, P., Bouchard, L., van Meel, E.R., Felix, J.F., Jaddoe, V.W.V., Yousefi, P.D., Ramlau‑Hansen, C.H., Relton, C.L., Tobi, E.W., Starling, A.P., Yang, I.V., Llambrich, M., Santorelli, G., Lepeule, J., Salas, L.A., Bustamante, M., Ewart, S.L., Zhang, H., Karmaus, W., Röder, Stefan, Zenclussen, Ana Claudia, Jin, J., Nystad, W., Page, C.M., Magnus, M., Jima, D.D., Hoyo, C., Maguire, R.L., Kvist, T., Czamara, D., Räikkönen, K., Gong, T., Ullemar, V., Rifas‐Shiman, S.L., Oken, E., Almqvist, C., Karlsson, R., Lahti, J., Murphy, S.K., Håberg, S.E., London, S., Herberth, Gunda, Arshad, H., Sunyer, J., Grazuleviciene, R., Dabelea, D., Steegers‑Theunissen, R.P.M., Nohr, E.A., Sørensen, T.I.A., Duijts, L., Hivert, M.-F., Nelen, V., Popovic, M., Kogevinas, M., Nawrot, T.S., Herceg, Z., Annesi-Maesano, I., Fallin, M.D., Yeung, E., Breton, C.V., Koletzko, B., Holland, N., Melén, E., Sharp, G.C., and Silver, M.J.
Abstract: BackgroundSeasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear.MethodsWe carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1–11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points.ResultsWe identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N).ConclusiosIn this large epigenome-wide meta-analysis study, we provide eviden
Published: 2023

7. Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

Author: Universitat Rovira i Virgili, Kadalayil, L; Alam, MZ; White, CH; Ghantous, A; Walton, E; Gruzieva, O; Merid, SK; Kumar, A; Roy, RP; Solomon, O; Huen, K; Eskenazi, B; Rzehak, P; Grote, V; Langhendries, JP; Verduci, E; Ferre, N; Gruszfeld, D; Gao, L; Guan, WH; Zeng, XH; Schisterman, EF; Dou, JF; Bakulski, KM; Feinberg, JI; Soomro, MH; Pesce, G; Baiz, N; Isaevska, E; Plusquin, M; Vafeiadi, M; Roumeliotaki, T; Langie, SAS; Standaert, A; Allard, C; Perron, P; Bouchard, L; van Meel, ER; Felix, JF; Jaddoe, VWV; Yousefi, PD; Ramlau-Hansen, CH; Relton, CL; Tobi, EW; Starling, AP; Yang, IV; Llambrich, M; Santorelli, G; Lepeule, J; Salas, LA; Bustamante, M; Ewart, SL; Zhang, HM; Karmaus, W; Röder, S; Zenclussen, AC; Jin, JP; Nystad, W; Page, CM; Magnus, M; Jima, DD; Hoyo, C; Maguire, RL; Kvist, T; Czamara, D; Räikkönen, K; Gong, T; Ullemar, V; Rifas-Shiman, SL; Oken, E; Almqvist, C; Karlsson, R; Lahti, J; Murphy, SK; Håberg, SE; London, S; Herberth, G; Arshad, H; Sunyer, J; Grazuleviciene, R; Dabelea, D; Steegers-Theunissen, RPM; Nohr, EA; Sorensen, TIA; Duijts, L; Hivert, MF; Nelen, V; Popovic, M; Kogevinas, M; Nawrot, TS; Herceg, Z; Annesi-Maesano, I; Fallin, MD; Yeung, EDA; Breton, CV; Koletzko, B; Holland, N; Wiemels, JL; Melén, E; Sharp, GC; Silver, MJ; Rezwan, F; Holloway, JW, Universitat Rovira i Virgili, and Kadalayil, L; Alam, MZ; White, CH; Ghantous, A; Walton, E; Gruzieva, O; Merid, SK; Kumar, A; Roy, RP; Solomon, O; Huen, K; Eskenazi, B; Rzehak, P; Grote, V; Langhendries, JP; Verduci, E; Ferre, N; Gruszfeld, D; Gao, L; Guan, WH; Zeng, XH; Schisterman, EF; Dou, JF; Bakulski, KM; Feinberg, JI; Soomro, MH; Pesce, G; Baiz, N; Isaevska, E; Plusquin, M; Vafeiadi, M; Roumeliotaki, T; Langie, SAS; Standaert, A; Allard, C; Perron, P; Bouchard, L; van Meel, ER; Felix, JF; Jaddoe, VWV; Yousefi, PD; Ramlau-Hansen, CH; Relton, CL; Tobi, EW; Starling, AP; Yang, IV; Llambrich, M; Santorelli, G; Lepeule, J; Salas, LA; Bustamante, M; Ewart, SL; Zhang, HM; Karmaus, W; Röder, S; Zenclussen, AC; Jin, JP; Nystad, W; Page, CM; Magnus, M; Jima, DD; Hoyo, C; Maguire, RL; Kvist, T; Czamara, D; Räikkönen, K; Gong, T; Ullemar, V; Rifas-Shiman, SL; Oken, E; Almqvist, C; Karlsson, R; Lahti, J; Murphy, SK; Håberg, SE; London, S; Herberth, G; Arshad, H; Sunyer, J; Grazuleviciene, R; Dabelea, D; Steegers-Theunissen, RPM; Nohr, EA; Sorensen, TIA; Duijts, L; Hivert, MF; Nelen, V; Popovic, M; Kogevinas, M; Nawrot, TS; Herceg, Z; Annesi-Maesano, I; Fallin, MD; Yeung, EDA; Breton, CV; Koletzko, B; Holland, N; Wiemels, JL; Melén, E; Sharp, GC; Silver, MJ; Rezwan, F; Holloway, JW
Abstract: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear.We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points.We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation inclu
Published: 2023

8. The contribution to policies of an exposome-based approach to childhood obesity

Author: Vineis, P, Handakas, E, Alfano, R, Millett, C, Fecht, D, Chatzi, L, Plusquin, M, Nawrot, T, Richiardi, L, Barros, H, Vrijheid, M, Sassi, F, Robinson, O, and Medical Research Council (MRC)
Subjects: Environmental Engineering
Abstract: Childhood obesity is an increasingly severe public health problem, with a prospective impact on health. We propose an exposome approach to identifying actionable risk factors for this condition. Our assumption is that relationships between external exposures and outcomes such as rapid growth, overweight or obesity in children can be better understood through a “meet-in-the-middle” model. This is based on a combination of external and internal exposome-based approaches, i.e. the study of multiple exposures (in our case dietary patterns) and molecular pathways (metabolomics and epigenetics). This may strengthen causal reasoning by identifying intermediate markers that are associated with both exposures and outcomes. Our biomarker-based studies in the STOP consortium suggest (in several ways, including mediation analysis) that Branched-Chain Amino Acids (BCAAs) could be mediators of the effect of dietary risk factors on childhood overweight/obesity. This is consistent with intervention and animal studies showing that higher intake of BCAAs has a positive impact on body composition, glycemia and satiety. Concerning food, of particular concern is the trend of increasing intake of ultra-processed food (UPF), including among children. Several mechanisms have been proposed to explain the impact of UPF on obesity and overweight, including nutrient intake (particularly proteins), changes in appetite or the role of additives. Research from the ALSPAC cohort has shown a relationship between UPF intake and trajectories in childhood adiposity, while UPF was related to lower blood levels of BCAAs. We suggest that an exposome-based approach can help strengthening causal reasoning and support policies. Intake of UPF in children should be restricted to prevent obesity.
Published: 2023
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9. Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Author: Solomon, O, Huen, K, Yousefi, P, Küpers, LK, González, JR, Suderman, M, Reese, SE, Page, CM, Gruzieva, O, Rzehak, P, Gao, L, Bakulski, KM, Novoloaca, A, Allard, C, Pappa, I, Llambrich, M, Vives, M, Jima, DD, Kvist, T, Baccarelli, A, White, C, Rezwan, FI, Sharp, GC, Tindula, G, Bergström, A, Grote, V, Dou, JF, Isaevska, E, Magnus, MC, Corpeleijn, E, Perron, P, Jaddoe, VWV, Nohr, EA, Maitre, L, Foraster, M, Hoyo, C, Håberg, SE, Lahti, J, DeMeo, DL, Zhang, H, Karmaus, W, Kull, I, Koletzko, B, Feinberg, JI, Gagliardi, L, Bouchard, L, Ramlau-Hansen, CH, Tiemeier, H, Santorelli, G, Maguire, RL, Czamara, D, Litonjua, AA, Langhendries, J-P, Plusquin, M, Lepeule, J, Binder, EB, Verduci, E, Dwyer, T, Carracedo, Á, Ferre, N, Eskenazi, B, Kogevinas, M, Nawrot, TS, Munthe-Kaas, MC, Herceg, Z, Relton, C, Melén, E, Gruszfeld, D, Breton, C, Fallin, MD, Ghantous, A, Nystad, W, Heude, B, Snieder, H, Hivert, M-F, Felix, JF, Sørensen, TIA, Bustamante, M, Murphy, SK, Raikkönen, K, Oken, E, Holloway, JW, Arshad, SH, London, SJ, Holland, N, Solomon, O, Huen, K, Yousefi, P, Küpers, LK, González, JR, Suderman, M, Reese, SE, Page, CM, Gruzieva, O, Rzehak, P, Gao, L, Bakulski, KM, Novoloaca, A, Allard, C, Pappa, I, Llambrich, M, Vives, M, Jima, DD, Kvist, T, Baccarelli, A, White, C, Rezwan, FI, Sharp, GC, Tindula, G, Bergström, A, Grote, V, Dou, JF, Isaevska, E, Magnus, MC, Corpeleijn, E, Perron, P, Jaddoe, VWV, Nohr, EA, Maitre, L, Foraster, M, Hoyo, C, Håberg, SE, Lahti, J, DeMeo, DL, Zhang, H, Karmaus, W, Kull, I, Koletzko, B, Feinberg, JI, Gagliardi, L, Bouchard, L, Ramlau-Hansen, CH, Tiemeier, H, Santorelli, G, Maguire, RL, Czamara, D, Litonjua, AA, Langhendries, J-P, Plusquin, M, Lepeule, J, Binder, EB, Verduci, E, Dwyer, T, Carracedo, Á, Ferre, N, Eskenazi, B, Kogevinas, M, Nawrot, TS, Munthe-Kaas, MC, Herceg, Z, Relton, C, Melén, E, Gruszfeld, D, Breton, C, Fallin, MD, Ghantous, A, Nystad, W, Heude, B, Snieder, H, Hivert, M-F, Felix, JF, Sørensen, TIA, Bustamante, M, Murphy, SK, Raikkönen, K, Oken, E, Holloway, JW, Arshad, SH, London, SJ, and Holland, N
Abstract: BACKGROUND: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. METHODS: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). RESULTS: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. CONCLUSIONS: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.
Published: 2022

10. Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation

Author: Universitat Rovira i Virgili, Solomon, O; Huen, K; Yousefi, P; Küpers, LK; González, JR; Suderman, M; Reese, SE; Page, CM; Gruzieva, O; Rzehak, P; Gao, L; Bakulski, KM; Novoloaca, A; Allard, C; Pappa, I; Llambrich, M; Vives, M; Jima, DD; Kvist, T; Baccarelli, A; White, C; Rezwan, FI; Sharp, GC; Tindula, G; Bergström, A; Grote, V; Dou, JF; Isaevska, E; Magnus, MC; Corpeleijn, E; Perron, P; Jaddoe, VWV; Nohr, EA; Maitre, L; Foraster, M; Hoyo, C; Håberg, SE; Lahti, J; DeMeo, DL; Zhang, HM; Karmaus, W; Kull, I; Koletzko, B; Feinberg, JI; Gagliardi, L; Bouchard, L; Ramlau-Hansen, CH; Tiemeier, H; Santorelli, G; Maguire, RL; Czamara, D; Litonjua, AA; Langhendries, JP; Plusquin, M; Lepeule, J; Binder, EB; Verduci, E; Dwyer, T; Carracedo, A; Ferre, N; Eskenazi, B; Kogevinas, M; Nawrot, TS; Munthe-Kaas, MC; Herceg, Z; Relton, C; Melén, E; Gruszfeld, D; Breton, C; Fallin, MD; Ghantous, A; Nystad, W; Heude, B; Snieder, H; Hivert, MF; Felix, JF; Sorensen, TIA; Bustamante, M; Murphy, SK; Raikkönen, K; Oken, E; Holloway, JW; Arshad, SH; London, SJ; Holland, N, Universitat Rovira i Virgili, and Solomon, O; Huen, K; Yousefi, P; Küpers, LK; González, JR; Suderman, M; Reese, SE; Page, CM; Gruzieva, O; Rzehak, P; Gao, L; Bakulski, KM; Novoloaca, A; Allard, C; Pappa, I; Llambrich, M; Vives, M; Jima, DD; Kvist, T; Baccarelli, A; White, C; Rezwan, FI; Sharp, GC; Tindula, G; Bergström, A; Grote, V; Dou, JF; Isaevska, E; Magnus, MC; Corpeleijn, E; Perron, P; Jaddoe, VWV; Nohr, EA; Maitre, L; Foraster, M; Hoyo, C; Håberg, SE; Lahti, J; DeMeo, DL; Zhang, HM; Karmaus, W; Kull, I; Koletzko, B; Feinberg, JI; Gagliardi, L; Bouchard, L; Ramlau-Hansen, CH; Tiemeier, H; Santorelli, G; Maguire, RL; Czamara, D; Litonjua, AA; Langhendries, JP; Plusquin, M; Lepeule, J; Binder, EB; Verduci, E; Dwyer, T; Carracedo, A; Ferre, N; Eskenazi, B; Kogevinas, M; Nawrot, TS; Munthe-Kaas, MC; Herceg, Z; Relton, C; Melén, E; Gruszfeld, D; Breton, C; Fallin, MD; Ghantous, A; Nystad, W; Heude, B; Snieder, H; Hivert, MF; Felix, JF; Sorensen, TIA; Bustamante, M; Murphy, SK; Raikkönen, K; Oken, E; Holloway, JW; Arshad, SH; London, SJ; Holland, N
Abstract: Background: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.
Published: 2022

11. A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Author: Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., Plusquin, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Reis, AlessanRSS/0000-0001-8486-7469, Chadeau-Hyam, Marc/0000-0001-8341-5436, Commission of the European Communities, Medical Research Council (MRC), Toxicogenomics, RS: FSE MaCSBio, RS: FPN MaCSBio, RS: FHML MaCSBio, RS: MHeNs - R3 - Neuroscience, and RS: GROW - R1 - Prevention
Subjects: ANTHROPOMETRY, Male, 0301 basic medicine, BMI, body mass index, Endocrinology, Diabetes and Metabolism, IQR, interquartile, Bioinformatics, Transcriptome, PC, phosphatidylcholine, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, LDL, low-density lipoprotein, FOR-GESTATIONAL-AGE, Birth weight, Cholesterol, DNA methylation, Gene expression, Metabolome, Proteins, Gestational age, DOHaD, Developmental Origin of Health and Disease, m/z, mass-to-charge ratio, Fetal Blood, INSULIN, In utero, Cord blood, Female, LGA, large for gestational age, Life Sciences & Biomedicine, LIPIDS, EXPRESSION, medicine.medical_specialty, HDL, high-density lipoprotein, 030209 endocrinology & metabolism, Biology, METABOLOMICS, Methylation, C-PEPTIDE, Article, 03 medical and health sciences, Endocrinology & Metabolism, Metabolomics, Internal medicine, medicine, Humans, EPIGENOME-WIDE ASSOCIATION, Chemokine CCL22, Science & Technology, Infant, Newborn, 1103 Clinical Sciences, Omics, AGA, adequate for gestational age, IL, interleukin, 95CI, 95% confidence interval, Cross-Sectional Studies, 030104 developmental biology, chemistry, COHORT PROFILE, ORA, overrepresentation analysis, U, unassigned metabolite, SGA, small for gestational age
Abstract: Background Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. Methods To investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts (n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations. Results This dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n = 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns. Conclusions Our data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight., Highlights • Using multiple omics, we provide an unprecedented window into the biological processes underlying birthweight. • We identified molecular signals never previously linked to birthweight, e.g. gene expression of JAK3 and chemokine CCL22. • Our data suggested that cholesterol and related metabolic pathways are related to birthweight. • The identified signals may create a molecular basis for the onset of health outcomes associated with birthweight variation.
Published: 2020

12. Prenatal Exposure to Multiple Air Pollutants, Mediating Molecular Mechanisms, and Shifts in Birthweight

Author: Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., Vineis, P., Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., and Vineis, P.
Abstract: Mechanisms underlying adverse birth and later in life health effects from exposure to air pollution during the prenatal period have not been not fully elucidated, especially in the context of mixtures. We assessed the effects of prenatal exposure to mixtures of air pollutants of particulate matter (PM), PM2.5, PM10, nitrogen oxides, NO2, NOx, ultrafine particles (UFP), and oxidative potential (OP) of PM2.5 on infant birthweight in four European birth cohorts and the mechanistic underpinnings through cross-omics of metabolites and inflammatory proteins. The association between mixtures of air pollutants and birthweight z-scores (standardized for gestational age) was assessed for three different mixture models, using Bayesian machine kernel regression (BKMR). We determined the direct effect for PM2.5, PM10, NO2, and mediation by cross-omic signatures (identified using sparse partial least-squares regression) using causal mediation BKMR models. There was a negative association with birthweight z-scores and exposure to mixtures of air pollutants, where up to −0.21 or approximately a 96 g decrease in birthweight, comparing the 75th percentile to the median level of exposure to the air pollutant mixture could occur. Shifts in birthweight z-scores from prenatal exposure to PM2.5, PM10, and NO2 were mediated by molecular mechanisms, represented by cross-omics scores. Interleukin-17 and epidermal growth factor were identified as important inflammatory responses underlyingair pollution-associated shifts in birthweight. Our results signify that by identifying mechanisms through which mixtures of air pollutants operate, the causality of air pollution-associated shifts in birthweight is better supported, substantiating the need for reducing exposure in vulnerable populations.
Published: 2020

13. 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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14. Prenatal Exposure to Multiple Air Pollutants, Mediating Molecular Mechanisms, and Shifts in Birthweight

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., Vineis, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., and Vineis, P.
Published: 2020

15. A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., Plusquin, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., and Plusquin, M.
Published: 2020

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

Author: Merid, SK, Novoloaca, A, Sharp, GC, Kupers, LK, Kho, AT, Roy, R, Gao, L, Annesi-Maesano, I, Jain, P, Plusquin, M, Kogevinas, M, Allard, C, Vehmeijer, FO, Kazmi, N, Salas, LA, Rezwan, FI, Zhang, H, Sebert, S, Czamara, D, Rifas-Shiman, SL, Melton, PE, Lawlor, DA, Pershagen, G, Breton, CV, Huen, K, Baiz, N, Gagliardi, L, Nawrot, TS, Corpeleijn, E, Perron, P, Duijts, L, Nohr, EA, Bustamante, M, Ewart, SL, Karmaus, W, Zhao, S, Page, CM, Herceg, Z, Jarvelin, M-R, Lahti, J, Baccarelli, AA, Anderson, D, Kachroo, P, Relton, CL, Bergstrom, A, Eskenazi, B, Soomro, MH, Vineis, P, Snieder, H, Bouchard, L, Jaddoe, VW, Sorensen, TIA, Vrijheid, M, Arshad, SH, Holloway, JW, Haberg, SE, Magnus, P, Dwyer, T, Binder, EB, DeMeo, DL, Vonk, JM, Newnham, J, Tantisira, KG, Kull, I, Wiemels, JL, Heude, B, Sunyer, J, Nystad, W, Munthe-Kaas, MC, Raikkonen, K, Oken, E, Huang, R-C, Weiss, ST, Anto, JM, Bousquet, J, Kumar, A, Soderhall, C, Almqvist, C, Cardenas, A, Gruzieva, O, Xu, C-J, Reese, SE, Kere, J, Brodin, P, Solomon, O, Wielscher, M, Holland, N, Ghantous, A, Hivert, M-F, Felix, JF, Koppelman, GH, London, SJ, Melen, E, Merid, SK, Novoloaca, A, Sharp, GC, Kupers, LK, Kho, AT, Roy, R, Gao, L, Annesi-Maesano, I, Jain, P, Plusquin, M, Kogevinas, M, Allard, C, Vehmeijer, FO, Kazmi, N, Salas, LA, Rezwan, FI, Zhang, H, Sebert, S, Czamara, D, Rifas-Shiman, SL, Melton, PE, Lawlor, DA, Pershagen, G, Breton, CV, Huen, K, Baiz, N, Gagliardi, L, Nawrot, TS, Corpeleijn, E, Perron, P, Duijts, L, Nohr, EA, Bustamante, M, Ewart, SL, Karmaus, W, Zhao, S, Page, CM, Herceg, Z, Jarvelin, M-R, Lahti, J, Baccarelli, AA, Anderson, D, Kachroo, P, Relton, CL, Bergstrom, A, Eskenazi, B, Soomro, MH, Vineis, P, Snieder, H, Bouchard, L, Jaddoe, VW, Sorensen, TIA, Vrijheid, M, Arshad, SH, Holloway, JW, Haberg, SE, Magnus, P, Dwyer, T, Binder, EB, DeMeo, DL, Vonk, JM, Newnham, J, Tantisira, KG, Kull, I, Wiemels, JL, Heude, B, Sunyer, J, Nystad, W, Munthe-Kaas, MC, Raikkonen, K, Oken, E, Huang, R-C, Weiss, ST, Anto, JM, Bousquet, J, Kumar, A, Soderhall, C, Almqvist, C, Cardenas, A, Gruzieva, O, Xu, C-J, Reese, SE, Kere, J, Brodin, P, Solomon, O, Wielscher, M, Holland, N, Ghantous, A, Hivert, M-F, Felix, JF, Koppelman, GH, London, SJ, and Melen, E
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

17. 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.), Kupers, L. K. (Leanne K.), 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. (Florianne O.), 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 L.), Melton, P. E. (Phillip E.), Lawlor, D. A. (Debbie A.), Pershagen, G. (Goran), Breton, C. V. (Carrie V.), Huen, K. (Karen), Baiz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T. S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, E. A. (Ellen Aagaard), Bustamante, M. (Mariona), Ewart, S. L. (Susan L.), 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 A.), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C. L. (Caroline L.), Bergstrom, A. (Anna), Eskenazi, B. (Brenda), Soomro, M. H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V. W. (Vincent W.), Sorensen, T. I. (Thorkild I. A.), Vrijheid, M. (Martine), Arshad, S. H. (S. Hasan), Holloway, J. W. (John W.), Haberg, S. E. (Siri E.), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E. B. (Elisabeth B.), DeMeo, D. L. (Dawn L.), Vonk, J. M. (Judith M.), Newnham, J. (John), Tantisira, K. G. (Kelan G.), Kull, I. (Inger), Wiemels, J. L. (Joseph L.), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M. C. (Monica C.), Raikkonen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S. T. (Scott T.), Anto, J. M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Soderhall, 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 F.), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Melen, E. (Erik), Merid, S. K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G. C. (Gemma C.), Kupers, L. K. (Leanne K.), 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. (Florianne O.), 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 L.), Melton, P. E. (Phillip E.), Lawlor, D. A. (Debbie A.), Pershagen, G. (Goran), Breton, C. V. (Carrie V.), Huen, K. (Karen), Baiz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T. S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, E. A. (Ellen Aagaard), Bustamante, M. (Mariona), Ewart, S. L. (Susan L.), 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 A.), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C. L. (Caroline L.), Bergstrom, A. (Anna), Eskenazi, B. (Brenda), Soomro, M. H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V. W. (Vincent W.), Sorensen, T. I. (Thorkild I. A.), Vrijheid, M. (Martine), Arshad, S. H. (S. Hasan), Holloway, J. W. (John W.), Haberg, S. E. (Siri E.), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E. B. (Elisabeth B.), DeMeo, D. L. (Dawn L.), Vonk, J. M. (Judith M.), Newnham, J. (John), Tantisira, K. G. (Kelan G.), Kull, I. (Inger), Wiemels, J. L. (Joseph L.), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M. C. (Monica C.), Raikkonen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S. T. (Scott T.), Anto, J. M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Soderhall, 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 F.), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), and Melen, 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

18. 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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19. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Author: Küpers, LK, Monnereau, C, Sharp, GC, Yousefi, P, Salas, LA, Ghantous, A, Page, CM, Reese, SE, Wilcox, AJ, Czamara, D, Starling, AP, Novoloaca, A, Lent, S, Roy, R, Hoyo, C, Breton, CV, Allard, C, Just, AC, Bakulski, KM, Holloway, JW, Everson, TM, Xu, C-J, Huang, R-C, van der Plaat, DA, Wielscher, M, Merid, SK, Ullemar, V, Rezwan, FI, Lahti, J, van Dongen, J, Langie, SAS, Richardson, TG, Magnus, MC, Nohr, EA, Xu, Z, Duijts, L, Zhao, S, Zhang, W, Plusquin, M, DeMeo, DL, Solomon, O, Heimovaara, JH, Jima, DD, Gao, L, Bustamante, M, Perron, P, Wright, RO, Hertz-Picciotto, I, Zhang, H, Karagas, MR, Gehring, U, Marsit, CJ, Beilin, LJ, Vonk, JM, Jarvelin, M-R, Bergström, A, Örtqvist, AK, Ewart, S, Villa, PM, Moore, SE, Willemsen, G, Standaert, ARL, Håberg, SE, Sørensen, TIA, Taylor, JA, Räikkönen, K, Yang, IV, Kechris, K, Nawrot, TS, Silver, MJ, Gong, YY, Richiardi, L, Kogevinas, M, Litonjua, AA, Eskenazi, B, Huen, K, Mbarek, H, Maguire, RL, Dwyer, T, Vrijheid, M, Bouchard, L, Baccarelli, AA, Croen, LA, Karmaus, W, Anderson, D, de Vries, M, Sebert, S, Kere, J, Karlsson, R, Arshad, SH, Hämäläinen, E, Routledge, MN, Boomsma, DI, Feinberg, AP, Newschaffer, CJ, Govarts, E, Moisse, M, Fallin, MD, Melén, E, Prentice, AM, Kajantie, E, Almqvist, C, Oken, E, Dabelea, D, Boezen, HM, Melton, PE, Wright, RJ, Koppelman, GH, Trevisi, L, Hivert, M-F, Sunyer, J, Munthe-Kaas, MC, Murphy, SK, Corpeleijn, E, Wiemels, J, Holland, N, Herceg, Z, Binder, EB, Davey Smith, G, Jaddoe, VWV, Lie, RT, Nystad, W, London, SJ, Lawlor, DA, Relton, CL, Snieder, H, Felix, JF, Küpers, LK, Monnereau, C, Sharp, GC, Yousefi, P, Salas, LA, Ghantous, A, Page, CM, Reese, SE, Wilcox, AJ, Czamara, D, Starling, AP, Novoloaca, A, Lent, S, Roy, R, Hoyo, C, Breton, CV, Allard, C, Just, AC, Bakulski, KM, Holloway, JW, Everson, TM, Xu, C-J, Huang, R-C, van der Plaat, DA, Wielscher, M, Merid, SK, Ullemar, V, Rezwan, FI, Lahti, J, van Dongen, J, Langie, SAS, Richardson, TG, Magnus, MC, Nohr, EA, Xu, Z, Duijts, L, Zhao, S, Zhang, W, Plusquin, M, DeMeo, DL, Solomon, O, Heimovaara, JH, Jima, DD, Gao, L, Bustamante, M, Perron, P, Wright, RO, Hertz-Picciotto, I, Zhang, H, Karagas, MR, Gehring, U, Marsit, CJ, Beilin, LJ, Vonk, JM, Jarvelin, M-R, Bergström, A, Örtqvist, AK, Ewart, S, Villa, PM, Moore, SE, Willemsen, G, Standaert, ARL, Håberg, SE, Sørensen, TIA, Taylor, JA, Räikkönen, K, Yang, IV, Kechris, K, Nawrot, TS, Silver, MJ, Gong, YY, Richiardi, L, Kogevinas, M, Litonjua, AA, Eskenazi, B, Huen, K, Mbarek, H, Maguire, RL, Dwyer, T, Vrijheid, M, Bouchard, L, Baccarelli, AA, Croen, LA, Karmaus, W, Anderson, D, de Vries, M, Sebert, S, Kere, J, Karlsson, R, Arshad, SH, Hämäläinen, E, Routledge, MN, Boomsma, DI, Feinberg, AP, Newschaffer, CJ, Govarts, E, Moisse, M, Fallin, MD, Melén, E, Prentice, AM, Kajantie, E, Almqvist, C, Oken, E, Dabelea, D, Boezen, HM, Melton, PE, Wright, RJ, Koppelman, GH, Trevisi, L, Hivert, M-F, Sunyer, J, Munthe-Kaas, MC, Murphy, SK, Corpeleijn, E, Wiemels, J, Holland, N, Herceg, Z, Binder, EB, Davey Smith, G, Jaddoe, VWV, Lie, RT, Nystad, W, London, SJ, Lawlor, DA, Relton, CL, Snieder, H, and Felix, JF
Abstract: Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
Published: 2019

20. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Author: Kupers, L. K. (Leanne K.), Monnereau, C. (Claire), Sharp, G. C. (Gemma C.), Yousefi, P. (Paul), Salas, L. A. (Lucas A.), Ghantous, A. (Akram), Page, C. M. (Christian M.), Reese, S. E. (Sarah E.), Wilcox, A. J. (Allen J.), Czamara, D. (Darina), Starling, A. P. (Anne P.), Novoloaca, A. (Alexei), Lent, S. (Samantha), Roy, R. (Ritu), Hoyo, C. (Cathrine), Breton, C. V. (Carrie, V), Allard, C. (Catherine), Just, A. C. (Allan C.), Bakulski, K. M. (Kelly M.), Holloway, J. W. (John W.), Everson, T. M. (Todd M.), Xu, C.-J. (Cheng-Jian), Huang, R.-C. (Rae-Chi), van der Plaat, D. A. (Diana A.), Wielscher, M. (Matthias), Merid, S. K. (Simon Kebede), Ullemar, V. (Vilhelmina), Rezwan, F. I. (Faisal, I), Lahti, J. (Jari), van Dongen, J. (Jenny), Langie, S. A. (Sabine A. S.), Richardson, T. G. (Tom G.), Magnus, M. C. (Maria C.), Nohr, E. A. (Ellen A.), Xu, Z. (Zongli), Duijts, L. (Liesbeth), Zhao, S. (Shanshan), Zhang, W. (Weiming), Plusquin, M. (Michelle), DeMeo, D. L. (Dawn L.), Solomon, O. (Olivia), Heimovaara, J. H. (Joosje H.), Jima, D. D. (Dereje D.), Gao, L. (Lu), Bustamante, M. (Mariona), Perron, P. (Patrice), Wright, R. O. (Robert O.), Hertz-Picciotto, I. (Irva), Zhang, H. (Hongmei), Karagas, M. R. (Margaret R.), Gehring, U. (Ulrike), Marsit, C. J. (Carmen J.), Beilin, L. J. (Lawrence J.), Vonk, J. M. (Judith M.), Jarvelin, M.-R. (Marjo-Riitta), Bergstrom, A. (Anna), Ortqvist, A. K. (Anne K.), Ewart, S. (Susan), Villa, P. M. (Pia M.), Moore, S. E. (Sophie E.), Willemsen, G. (Gonneke), Standaert, A. R. (Arnout R. L.), Haberg, S. E. (Siri E.), Sorensen, T. I. (Thorkild I. A.), Taylor, J. A. (Jack A.), Raikkonen, K. (Katri), Yang, I. V. (Ivana, V), Kechris, K. (Katerina), Nawrot, T. S. (Tim S.), Silver, M. J. (Matt J.), Gong, Y. Y. (Yun Yun), Richiardi, L. (Lorenzo), Kogevinas, M. (Manolis), Litonjua, A. A. (Augusto A.), Eskenazi, B. (Brenda), Huen, K. (Karen), Mbarek, H. (Hamdi), Maguire, R. L. (Rachel L.), Dwyer, T. (Terence), Vrijheid, M. (Martine), Bouchard, L. (Luigi), Baccarelli, A. A. (Andrea A.), Croen, L. A. (Lisa A.), Karmaus, W. (Wilfried), Anderson, D. (Denise), de Vries, M. (Maaike), Sebert, S. (Sylvain), Kere, J. (Juha), Karlsson, R. (Robert), Arshad, S. H. (Syed Hasan), Hamalainen, E. (Esa), Routledge, M. N. (Michael N.), Boomsma, D. I. (Dorret, I), Feinberg, A. P. (Andrew P.), Newschaffer, C. J. (Craig J.), Govarts, E. (Eva), Moisse, M. (Matthieu), Fallin, M. D. (M. Daniele), Melen, E. (Erik), Prentice, A. M. (Andrew M.), Kajantie, E. (Eero), Almqvist, C. (Catarina), Oken, E. (Emily), Dabelea, D. (Dana), Boezen, H. M. (H. Marike), Melton, P. E. (Phillip E.), Wright, R. J. (Rosalind J.), Koppelman, G. H. (Gerard H.), Trevisi, L. (Letizia), Hivert, M.-F. (Marie-France), Sunyer, J. (Jordi), Munthe-Kaas, M. C. (Monica C.), Murphy, S. K. (Susan K.), Corpeleijn, E. (Eva), Wiemels, J. (Joseph), Holland, N. (Nina), Herceg, Z. (Zdenko), Binder, E. B. (Elisabeth B.), Smith, G. D. (George Davey), Jaddoe, V. W. (Vincent W. V.), Lie, R. T. (Rolv T.), Nystad, W. (Wenche), London, S. J. (Stephanie J.), Lawlor, D. A. (Debbie A.), Relton, C. L. (Caroline L.), Snieder, H. (Harold), Felix, J. F. (Janine F.), Kupers, L. K. (Leanne K.), Monnereau, C. (Claire), Sharp, G. C. (Gemma C.), Yousefi, P. (Paul), Salas, L. A. (Lucas A.), Ghantous, A. (Akram), Page, C. M. (Christian M.), Reese, S. E. (Sarah E.), Wilcox, A. J. (Allen J.), Czamara, D. (Darina), Starling, A. P. (Anne P.), Novoloaca, A. (Alexei), Lent, S. (Samantha), Roy, R. (Ritu), Hoyo, C. (Cathrine), Breton, C. V. (Carrie, V), Allard, C. (Catherine), Just, A. C. (Allan C.), Bakulski, K. M. (Kelly M.), Holloway, J. W. (John W.), Everson, T. M. (Todd M.), Xu, C.-J. (Cheng-Jian), Huang, R.-C. (Rae-Chi), van der Plaat, D. A. (Diana A.), Wielscher, M. (Matthias), Merid, S. K. (Simon Kebede), Ullemar, V. (Vilhelmina), Rezwan, F. I. (Faisal, I), Lahti, J. (Jari), van Dongen, J. (Jenny), Langie, S. A. (Sabine A. S.), Richardson, T. G. (Tom G.), Magnus, M. C. (Maria C.), Nohr, E. A. (Ellen A.), Xu, Z. (Zongli), Duijts, L. (Liesbeth), Zhao, S. (Shanshan), Zhang, W. (Weiming), Plusquin, M. (Michelle), DeMeo, D. L. (Dawn L.), Solomon, O. (Olivia), Heimovaara, J. H. (Joosje H.), Jima, D. D. (Dereje D.), Gao, L. (Lu), Bustamante, M. (Mariona), Perron, P. (Patrice), Wright, R. O. (Robert O.), Hertz-Picciotto, I. (Irva), Zhang, H. (Hongmei), Karagas, M. R. (Margaret R.), Gehring, U. (Ulrike), Marsit, C. J. (Carmen J.), Beilin, L. J. (Lawrence J.), Vonk, J. M. (Judith M.), Jarvelin, M.-R. (Marjo-Riitta), Bergstrom, A. (Anna), Ortqvist, A. K. (Anne K.), Ewart, S. (Susan), Villa, P. M. (Pia M.), Moore, S. E. (Sophie E.), Willemsen, G. (Gonneke), Standaert, A. R. (Arnout R. L.), Haberg, S. E. (Siri E.), Sorensen, T. I. (Thorkild I. A.), Taylor, J. A. (Jack A.), Raikkonen, K. (Katri), Yang, I. V. (Ivana, V), Kechris, K. (Katerina), Nawrot, T. S. (Tim S.), Silver, M. J. (Matt J.), Gong, Y. Y. (Yun Yun), Richiardi, L. (Lorenzo), Kogevinas, M. (Manolis), Litonjua, A. A. (Augusto A.), Eskenazi, B. (Brenda), Huen, K. (Karen), Mbarek, H. (Hamdi), Maguire, R. L. (Rachel L.), Dwyer, T. (Terence), Vrijheid, M. (Martine), Bouchard, L. (Luigi), Baccarelli, A. A. (Andrea A.), Croen, L. A. (Lisa A.), Karmaus, W. (Wilfried), Anderson, D. (Denise), de Vries, M. (Maaike), Sebert, S. (Sylvain), Kere, J. (Juha), Karlsson, R. (Robert), Arshad, S. H. (Syed Hasan), Hamalainen, E. (Esa), Routledge, M. N. (Michael N.), Boomsma, D. I. (Dorret, I), Feinberg, A. P. (Andrew P.), Newschaffer, C. J. (Craig J.), Govarts, E. (Eva), Moisse, M. (Matthieu), Fallin, M. D. (M. Daniele), Melen, E. (Erik), Prentice, A. M. (Andrew M.), Kajantie, E. (Eero), Almqvist, C. (Catarina), Oken, E. (Emily), Dabelea, D. (Dana), Boezen, H. M. (H. Marike), Melton, P. E. (Phillip E.), Wright, R. J. (Rosalind J.), Koppelman, G. H. (Gerard H.), Trevisi, L. (Letizia), Hivert, M.-F. (Marie-France), Sunyer, J. (Jordi), Munthe-Kaas, M. C. (Monica C.), Murphy, S. K. (Susan K.), Corpeleijn, E. (Eva), Wiemels, J. (Joseph), Holland, N. (Nina), Herceg, Z. (Zdenko), Binder, E. B. (Elisabeth B.), Smith, G. D. (George Davey), Jaddoe, V. W. (Vincent W. V.), Lie, R. T. (Rolv T.), Nystad, W. (Wenche), London, S. J. (Stephanie J.), Lawlor, D. A. (Debbie A.), Relton, C. L. (Caroline L.), Snieder, H. (Harold), and Felix, J. F. (Janine F.)
Abstract: Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
Published: 2019

21. Prenatal particulate air pollution and DNA methylation in newborns: An epigenome-wide meta-analysis

Author: Gruzieva, O., Xu, Cheng-Jian, Yousefi, P., Relton, C., Merid, S. K., Breton, C. V., Gao, L., Volk, H. E., Feinberg, J. I., Ladd-Acosta, C., Bakulski, K., Auffray, C., Lemonnier, N., Plusquin, M., Ghantous, A., Herceg, Z., Nawrot, T. S., Pizzi, C., Richiardi, L., Rusconi, Franca, Vineis, P., Kogevinas, M., Felix, Janine F, Duijts, L., Den Dekker, H. T., Jaddoe, V. W. V., Ruiz, José L., Bustamante, M., Antó, Josep M., Sunyer, J., Vrijheid, M., Gutzkow, K.B., Grazuleviciene, R., Hernandez-Ferrer, C., Annesi-Maesano, I., Lepeule, J., Bousquet, J., Bergström, A., Kull, I., Söderhäll, C., Kere, J., Gehring, U., Brunekreef, B., Just, A.C., Wright, R.J., Peng, C., Gold, D.R., Kloog, I., Demeo, D.L., Gruzieva, O., Xu, Cheng-Jian, Yousefi, P., Relton, C., Merid, S. K., Breton, C. V., Gao, L., Volk, H. E., Feinberg, J. I., Ladd-Acosta, C., Bakulski, K., Auffray, C., Lemonnier, N., Plusquin, M., Ghantous, A., Herceg, Z., Nawrot, T. S., Pizzi, C., Richiardi, L., Rusconi, Franca, Vineis, P., Kogevinas, M., Felix, Janine F, Duijts, L., Den Dekker, H. T., Jaddoe, V. W. V., Ruiz, José L., Bustamante, M., Antó, Josep M., Sunyer, J., Vrijheid, M., Gutzkow, K.B., Grazuleviciene, R., Hernandez-Ferrer, C., Annesi-Maesano, I., Lepeule, J., Bousquet, J., Bergström, A., Kull, I., Söderhäll, C., Kere, J., Gehring, U., Brunekreef, B., Just, A.C., Wright, R.J., Peng, C., Gold, D.R., Kloog, I., and Demeo, D.L.
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 <10 (PM)or<2:5 lm (PM) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to PM (n = 1,949) and PM (n = 1,551) 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 associated [false discovery rate (FDR) <0:05] with prenatal PM and 14 with PM exposure. Two of the PM-related CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant (p <0:05) in 7-to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent PM exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM and or PM exposure, of which two PM-related DMRs, including H19 and MARCH11, replicated in newborns. CONCLUSIONS: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.
Published: 2019

22. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author: Felix, JF, Joubert, BR, Baccarelli, AA, Sharp, GC, Almqvist, C, Annesi-Maesano, I, Arshad, H, Baïz, N, Bakermans-Kranenburg, MJ, Bakulski, KM, Binder, EB, Bouchard, L, Breton, CV, Brunekreef, B, Brunst, KJ, Burchard, EG, Bustamante, M, Chatzi, L, Munthe-Kaas, M, Corpeleijn, E, Czamara, D, Dabelea, D, Smith, G, De Boever, P, Duijts, L, Dwyer, T, Eng, C, Eskenazi, B, Everson, TM, Falahi, F, Fallin, MD, Farchi, S, Fernandez, MF, Gao, L, Gaunt, TR, Ghantous, A, Gillman, MW, Gonseth, S, Grote, V, Gruzieva, O, Håberg, SE, Herceg, Z, Hivert, M-F, Holland, N, Holloway, JW, Hoyo, C, Hu, D, Huang, R-C, Huen, K, Järvelin, M-R, Jima, DD, Just, AC, Karagas, MR, Karlsson, R, Karmaus, W, Kechris, KJ, Kere, J, Kogevinas, M, Koletzko, B, Koppelman, GH, Küpers, LK, Ladd-Acosta, C, Lahti, J, Lambrechts, N, Langie, SAS, Lie, RT, Liu, AH, Magnus, MC, Magnus, P, Maguire, RL, Marsit, CJ, McArdle, W, Melén, E, Melton, P, Murphy, SK, Nawrot, TS, Nisticò, L, Nohr, EA, Nordlund, B, Nystad, W, Oh, SS, Oken, E, Page, CM, Perron, P, Pershagen, G, Pizzi, C, Plusquin, M, Raikkonen, K, Reese, SE, Reischl, E, Richiardi, L, Ring, S, Roy, RP, Rzehak, P, Schoeters, G, Schwartz, DA, Sebert, S, Snieder, H, Sørensen, TIA, Starling, AP, Sunyer, J, Taylor, JA, Tiemeier, H, Ullemar, V, Vafeiadi, M, Van Ijzendoorn, MH, Vonk, JM, Vriens, A, Vrijheid, M, Wang, P, Wiemels, JL, Wilcox, AJ, Wright, RJ, Xu, C-J, Xu, Z, Yang, IV, Yousefi, P, Zhang, H, Zhang, W, Zhao, S, Agha, G, Relton, CL, Jaddoe, VWV, London, SJ, Epidemiology, Erasmus MC other, Pediatrics, Child and Adolescent Psychiatry / Psychology, Psychiatry, Research Methods and Techniques, dIRAS RA-2, One Health Chemisch, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Department of Psychology and Logopedics, Helsinki Collegium for Advanced Studies, Medicum, University of Helsinki, and Developmental Psychology Research Group
Subjects: DNA Methylation/physiology, Epidemiology, Maternal Health, education, Embaràs, DISEASE, Environmental Pollution/analysis, Epigenesis, Genetic, Cohort Studies, Prenatal Exposure Delayed Effects/epidemiology, Folic Acid, Pregnancy, Journal Article, Humans, MATERNAL SMOKING, CORD BLOOD, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Cohort Profiles, METAANALYSIS, PRENATAL EXPOSURE, Maternal Exposure/adverse effects, EPIGENOME-WIDE ASSOCIATION, 0104 Statistics, Child Health, Infant, Newborn, DNA METHYLATION DATA, DNA Methylation, Epigenètica, BIRTH-WEIGHT, 3142 Public health care science, environmental and occupational health, Folic Acid/blood, 1117 Public Health And Health Services, Maternal Exposure, Prenatal Exposure Delayed Effects, MENDELIAN RANDOMIZATION, Epigenetics, Female, Human medicine, Environmental Pollution
Abstract: UK Medical Research Council; Wellcome Trust [102215/2/13/2, WT088806, 084762MA]; UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]; UK Medical Research Council Integrative Epidemiology Unit; University of Bristol [MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8]; United States National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK10324]; Swedish Research Council; Swedish Heart-Lung Foundation; Freemason Child House Foundation in Stockholm; MeDALL (Mechanisms of the Development of ALLergy), within the European Union [261357]; Stockholm County Council (ALF); Swedish Foundation for Strategic Research (SSF) [RBc08-0027]; Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet; Swedish Research Council Formas; Swedish Environment Protection Agency; Center for Integrative Research on Childhood Leukemia and the Environment [P01ES018172]; NIH [P50ES018172, R01ES09137, 5P30CA082103, P01 ES009605, R01 ES021369, R01ES023067, K01ES017801, R01ES022216, P30ES007048, R01ES014447, P01ES009581, R826708-01, RD831861-01, P50ES026086, R01DK068001, R01 DK100340, R01 DK076648, R01ES022934, R01HL111108, R01NR013945, R37 HD034568, UL1 TR001082, P30 DK56350]; EPA [RD83451101, RD83615901, RD 82670901, RD 83451301, 83615801-0]; UCSF Comprehensive Cancer Center Support grant [P30 CA82103]; Swiss Science National Foundation [P2LAP3_158674]; Sutter-Stottner Foundation; Commission of the European Community, specific RTD Programme 'Quality of Life and Management of Living Resources' within the 5th Framework Programme [QLRT-2001-00389, QLK1-CT-2002-30582]; 6th Framework Programme [007036]; European Union's Seventh Framework Programme (FP7), project EarlyNutrition [289346]; European Research Council Advanced grant ERC-AdG [322605 META-GROWTH]; Autism Speaks grant [260377]; Funds for Research in Respiratory Health; French Ministry of Research: IFR program; INSERM Nutrition Research Program; French Ministry of Health: Perinatality Program; French National Institute for Population Health Surveillance (INVS); Paris-Sud University; French National Institute for Health Education (INPES); Nestle; Mutuelle Generale de l'Education Nationale (MGEN); French-speaking association for the study of diabetes and metabolism (Alfediam) [2012/51290-6]; EU; European Research Council [ERC-2012-StG.310898, 268479-BREATHE]; Flemish Scientific Research Council (FWO) [N1516112 / G.0.873.11N.10]; European Community's Seventh Framework Programme FP7 project EXPOsOMICS [308610]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA grant [628858]; Bijzonder Onderzoeksfonds (BOF) Hasselt University; Ministry of the Flemish Community (Department of Economics, Science and Innovation); Ministry of the Flemish Community (Department of Environment, Nature and Energy); CEFIC LRI award by the Research Foundation-Flanders (FWO); CEFIC LRI award by the Research Foundation-Flanders (FWO) [12L5216N]; Flemish Institute for Technological Research (VITO) [12L5216N]; Bill AMP; Melinda Gates Foundation Grand Challenges Exploration grant [OPP119403]; Sandler Family Foundation; American Asthma Foundation; National Institutes of Health; National Heart, Lung and Blood Institute [HL117004]; National Institute of Environmental Health Sciences [ES24844]; National Institute on Minority Health and Health Disparities [MD006902, MD009523]; National Institute of General Medical Sciences [GM007546]; Tobacco-Related Disease Research Program [24RT-0025]; Hutchison Whampoa Ltd, Hong Kong; University of Groningen; Well Baby Clinic Foundation Icare; Noordlease; Youth Health Care Drenthe; Biobanking and Biomolecular Research Infrastructure Netherlands [CP2011-19]; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; European Union's Horizon research and innovation programme [733206, 633595]; National Institute of Child and Human Development [R01HD068437]; Netherlands Organization for Health Research and Development [VIDI 016.136.361]; Consolidator grant from the European Research Council [ERC-2014-CoG-648916]; Netherlands' Organization for Scientific Research (NWO VICI); European Research Council ERC; Netherlands' Organization for Scientific Research (NWO Spinoza Award); Gravitation program of the Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO) [024.001.003]; Lung Foundation Netherlands [3.2.12.089]; Fonds de Recherche du Quebec en Sante (FRQ-S) [20697]; Canadian Institute of Health Reseach (CIHR) [MOP 115071]; Diabete Quebec grant; Canadian Diabetes Association operating grant [OG-3-08-2622]; American Diabetes Association Pathways Accelerator Early Investigator Award [1-15-ACE-26]; MRC Integrative Epidemiology Unit - Medical Research Council [MC_UU_12013/1-9]; National Institute of Environmental Health Sciences, National Institutes of Health [K99ES025817]; Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041]; Spanish Ministry of Health [FIS-PI04/1436, FIS-PI08/1151]; Spanish Ministry of Health (FEDER funds) [FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615]; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Fundacio La Marato de TV3 [090430]; EU Commission [261357-MeDALL]; National Institute of Allergy and Infectious Diseases [N01-AI90052]; National Institutes of Health USA [R01 HL082925, R01 HL132321]; Asthma UK [364]; NIAID/NIH [R01AI091905, R01AI121226]; National Institute of Health [R01AI121226, R01 AI091905, R01HL132321]; NIH/NIEHS [N01-ES75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES-49019, Z01 ES044005, ES049033, ES049032]; Norwegian Research Council/BIOBANK [221097]; Oslo University Hospital; Unger-Vetlesens foundation; Norwegian American Womens Club; INCA/Plan Cancer-EVA-INSERM, France; International Childhood Cancer Cohort Consortium (I4C); INCA/Plan Cancer-EVA-INSERM (France); IARC Postdoctoral Fellowship; EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND); NIEHS [R21ES014947, R01ES016772]; NIDDK [R01DK085173]; National Institute of Environmental Health Science [P30 ES025128]; University of Oulu grant [65354]; Oulu University Hospital [2/97, 8/97]; Ministry of Health and Social Affairs [23/251/97, 160/97, 190/97]; National Institute for Health and Welfare, Helsinki [54121]; Regional Institute of Occupational Health, Oulu, Finland [50621, 54231]; EU [QLG1-CT-2000-01643, E51560]; NorFA grant [731, 20056, 30167]; Academy of Finland; NIH-NIEHS [P01 ES022832]; US EPA [RD83544201]; NIH-NIGMS [P20GM104416]; NCI [R25CA134286]; Netherlands Organization for Scientific Research and Development; Netherlands Asthma Fund; Netherlands Ministry of Spatial Planning, Housing, and the Environment; Netherlands Ministry of Health, Welfare, and Sport; MeDALL; European Union under the Health Cooperation Work Program of the 7th Framework program [261357]; Italian National Centre for Disease Prevention and Control (CCM grant); Italian Ministry of Health (art 12); Italian Ministry of Health (12bis Dl.gs.vo) [502/92]; EraNet; EVO; University of Helsinki Research Funds; Signe and Ane Gyllenberg foundation; Emil Aaltonen Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; University of Helsinki; University of Western Australia (UWA); Curtin University; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women's and Infant's Research Foundation (KEMH); Edith Cowan University; National Health and Medical Research Council [1059711]; National Health and Medical Research Council (NHMRC) fellowship [1053384]; Australian National Health and Medical Research Council; United States National Institute of Health; Greek Ministry of Health (programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece); Greek Ministry of Health ('Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health); European Union (EU) [EU FP6-2003-Food-3-NewGeneris, EU FP7 ENV.2007.1.2.2.2, 211250 ESCAPE, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7 ENV.2008.1.2.1.6, 226285 ENRIECO]; National Institutes of Health [NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, NIH-NIEHS R01ES025145]; Centers for Disease Control and Prevention [U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498]; Autism Speaks [7659]; Swedish Research Council through the Swedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF projects); Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Asthma and Allergy Association's Research Foundation; Stiftelsen Frimurare Barnahuset Stockholm; Norwegian Ministry of Health and Care Services; Ministry of the Flemish Community (Flemish Agency for Care and Health); University of Bristol; Ministry of Education and Research; European Union (EU) (EU FP7-HEALTH-single stage CHICOS); European Union (EU) (EU-FP7-HEALTH) [308333 HELIX]; European Union (EU) (EU FP6. STREP HiWATE); UK Medical Research Council; Wellcome Trust [102215/2/13/2, WT088806, 084762MA]; UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]; UK Medical Research Council Integrative Epidemiology Unit; University of Bristol [MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8]; United States National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK10324]; Swedish Research Council; Swedish Heart-Lung Foundation; Freemason Child House Foundation in Stockholm; MeDALL (Mechanisms of the Development of ALLergy), within the European Union [261357]; Stockholm County Council (ALF); Swedish Foundation for Strategic Research (SSF) [RBc08-0027]; Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet; Swedish Research Council Formas; Swedish Environment Protection Agency; Center for Integrative Research on Childhood Leukemia and the Environment [P01ES018172]; NIH [P50ES018172, R01ES09137, 5P30CA082103, P01 ES009605, R01 ES021369, R01ES023067, K01ES017801, R01ES022216, P30ES007048, R01ES014447, P01ES009581, R826708-01, RD831861-01, P50ES026086, R01DK068001, R01 DK100340, R01 DK076648, R01ES022934, R01HL111108, R01NR013945, R37 HD034568, UL1 TR001082, P30 DK56350]; EPA [RD83451101, RD83615901, RD 82670901, RD 83451301, 83615801-0]; UCSF Comprehensive Cancer Center Support grant [P30 CA82103]; Swiss Science National Foundation [P2LAP3_158674]; Sutter-Stottner Foundation; Commission of the European Community, specific RTD Programme 'Quality of Life and Management of Living Resources' within the 5th Framework Programme [QLRT-2001-00389, QLK1-CT-2002-30582]; 6th Framework Programme [007036]; European Union's Seventh Framework Programme (FP7), project EarlyNutrition [289346]; European Research Council Advanced grant ERC-AdG [322605 META-GROWTH]; Autism Speaks grant [260377]; Funds for Research in Respiratory Health; French Ministry of Research: IFR program; INSERM Nutrition Research Program; French Ministry of Health: Perinatality Program; French National Institute for Population Health Surveillance (INVS); Paris-Sud University; French National Institute for Health Education (INPES); Nestle; Mutuelle Generale de l'Education Nationale (MGEN); French-speaking association for the study of diabetes and metabolism (Alfediam) [2012/51290-6]; EU; European Research Council [ERC-2012-StG.310898, 268479-BREATHE]; Flemish Scientific Research Council (FWO) [N1516112 / G.0.873.11N.10]; European Community's Seventh Framework Programme FP7 project EXPOsOMICS [308610]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA grant [628858]; Bijzonder Onderzoeksfonds (BOF) Hasselt University; Ministry of the Flemish Community (Department of Economics, Science and Innovation); Ministry of the Flemish Community (Department of Environment, Nature and Energy); CEFIC LRI award by the Research Foundation-Flanders (FWO); CEFIC LRI award by the Research Foundation-Flanders (FWO) [12L5216N]; Flemish Institute for Technological Research (VITO) [12L5216N]; Bill AMP; Melinda Gates Foundation Grand Challenges Exploration grant [OPP119403]; Sandler Family Foundation; American Asthma Foundation; National Institutes of Health; National Heart, Lung and Blood Institute [HL117004]; National Institute of Environmental Health Sciences [ES24844]; National Institute on Minority Health and Health Disparities [MD006902, MD009523]; National Institute of General Medical Sciences [GM007546]; Tobacco-Related Disease Research Program [24RT-0025]; Hutchison Whampoa Ltd, Hong Kong; University of Groningen; Well Baby Clinic Foundation Icare; Noordlease; Youth Health Care Drenthe; Biobanking and Biomolecular Research Infrastructure Netherlands [CP2011-19]; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; European Union's Horizon research and innovation programme [733206, 633595]; National Institute of Child and Human Development [R01HD068437]; Netherlands Organization for Health Research and Development [VIDI 016.136.361]; Consolidator grant from the European Research Council [ERC-2014-CoG-648916]; Netherlands' Organization for Scientific Research (NWO VICI); European Research Council ERC; Netherlands' Organization for Scientific Research (NWO Spinoza Award); Gravitation program of the Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO) [024.001.003]; Lung Foundation Netherlands [3.2.12.089]; Fonds de Recherche du Quebec en Sante (FRQ-S) [20697]; Canadian Institute of Health Reseach (CIHR) [MOP 115071]; Diabete Quebec grant; Canadian Diabetes Association operating grant [OG-3-08-2622]; American Diabetes Association Pathways Accelerator Early Investigator Award [1-15-ACE-26]; MRC Integrative Epidemiology Unit - Medical Research Council [MC_UU_12013/1-9]; National Institute of Environmental Health Sciences, National Institutes of Health [K99ES025817]; Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041]; Spanish Ministry of Health [FIS-PI04/1436, FIS-PI08/1151]; Spanish Ministry of Health (FEDER funds) [FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615]; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Fundacio La Marato de TV3 [090430]; EU Commission [261357-MeDALL]; National Institute of Allergy and Infectious Diseases [N01-AI90052]; National Institutes of Health USA [R01 HL082925, R01 HL132321]; Asthma UK [364]; NIAID/NIH [R01AI091905, R01AI121226]; National Institute of Health [R01AI121226, R01 AI091905, R01HL132321]; NIH/NIEHS [N01-ES75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES-49019, Z01 ES044005, ES049033, ES049032]; Norwegian Research Council/BIOBANK [221097]; Oslo University Hospital; Unger-Vetlesens foundation; Norwegian American Womens Club; INCA/Plan Cancer-EVA-INSERM, France; International Childhood Cancer Cohort Consortium (I4C); INCA/Plan Cancer-EVA-INSERM (France); IARC Postdoctoral Fellowship; EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND); NIEHS [R21ES014947, R01ES016772]; NIDDK [R01DK085173]; National Institute of Environmental Health Science [P30 ES025128]; University of Oulu grant [65354]; Oulu University Hospital [2/97, 8/97]; Ministry of Health and Social Affairs [23/251/97, 160/97, 190/97]; National Institute for Health and Welfare, Helsinki [54121]; Regional Institute of Occupational Health, Oulu, Finland [50621, 54231]; EU [QLG1-CT-2000-01643, E51560]; NorFA grant [731, 20056, 30167]; Academy of Finland; NIH-NIEHS [P01 ES022832]; US EPA [RD83544201]; NIH-NIGMS [P20GM104416]; NCI [R25CA134286]; Netherlands Organization for Scientific Research and Development; Netherlands Asthma Fund; Netherlands Ministry of Spatial Planning, Housing, and the Environment; Netherlands Ministry of Health, Welfare, and Sport; MeDALL; European Union under the Health Cooperation Work Program of the 7th Framework program [261357]; Italian National Centre for Disease Prevention and Control (CCM grant); Italian Ministry of Health (art 12); Italian Ministry of Health (12bis Dl.gs.vo) [502/92]; EraNet; EVO; University of Helsinki Research Funds; Signe and Ane Gyllenberg foundation; Emil Aaltonen Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; University of Helsinki; University of Western Australia (UWA); Curtin University; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women's and Infant's Research Foundation (KEMH); Edith Cowan University; National Health and Medical Research Council [1059711]; National Health and Medical Research Council (NHMRC) fellowship [1053384]; Australian National Health and Medical Research Council; United States National Institute of Health; Greek Ministry of Health (programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece); Greek Ministry of Health ('Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health); European Union (EU) [EU FP6-2003-Food-3-NewGeneris, EU FP7 ENV.2007.1.2.2.2, 211250 ESCAPE, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7 ENV.2008.1.2.1.6, 226285 ENRIECO]; National Institutes of Health [NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, NIH-NIEHS R01ES025145]; Centers for Disease Control and Prevention [U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498]; Autism Speaks [7659]; Swedish Research Council through the Swedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF projects); Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Asthma and Allergy Association's Research Foundation; Stiftelsen Frimurare Barnahuset Stockholm; Norwegian Ministry of Health and Care Services; Ministry of the Flemish Community (Flemish Agency for Care and Health); University of Bristol; Ministry of Education and Research; European Union (EU) (EU FP7-HEALTH-single stage CHICOS); European Union (EU) (EU-FP7-HEALTH) [308333 HELIX]; European Union (EU) (EU FP6. STREP HiWATE); [R01ES017646]; [R01ES01900]; [R01ES16443]; [USA / NIHH 2000 G DF682]; [50945]; [R01 HL095606]; [R01 HL1143396]
Published: 2018
Full Text: View/download PDF

23. Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium

Author: Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), London, S.J. (Stephanie J.), Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), and London, S.J. (Stephanie J.)
Published: 2018
Full Text: View/download PDF

24. Cohort profile:pregnancy and childhood epigenetics (PACE) consortium

Author: Felix, J. F. (Janine F.), Joubert, B. R. (Bonnie R.), Baccarelli, A. A. (Andrea A.), Sharp, G. C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baiz, N. (Nour), Bakermans-Kranenburg, M. J. (Marian J.), Bakulski, K. M. (Kelly M.), Binder, E. B. (Elisabeth B.), Bouchard, L. (Luigi), Breton, C. V. (Carrie V.), Brunekreef, B. (Bert), Brunst, K. J. (Kelly J.), Burchard, E. G. (Esteban G.), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M. C. (Monica Cheng), Corpeleijn, E. (Eva), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G. D. (George Davey), De Boever, P. (Patrick), Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (Brenda), Everson, T. M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M. D. (M. Daniele), Farchi, S. (Sara), Fernandez, M. F. (Mariana F.), Gao, L. (Lu), Gaunt, T. R. (Tom R.), Ghantous, A. (Akram), Gillman, M. W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Haberg, S. E. (Siri E.), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J. W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D. D. (Dereje D.), Just, A. C. (Allan C.), Karagas, M. R. (Margaret R.), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K. J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G. H. (Gerard H.), Kupers, L. K. (Leanne K.), Ladd-Acosta, C. (Christine), Lahti, J. (Jari), Lambrechts, N. (Nathalie), Langie, S. A. (Sabine A. S.), Lie, R. T. (Rolv T.), Liu, A. H. (Andrew H.), Magnus, M. C. (Maria C.), Magnus, P. (Per), Maguire, R. L. (Rachel L.), Marsit, C. J. (Carmen J.), McArdle, W. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S. K. (Susan K.), Nawrot, T. S. (Tim S.), Nistico, L. (Lorenza), Nohr, E. A. (Ellen A.), Nordlund, B. (Bjorn), Nystad, W. (Wenche), Oh, S. S. (Sam S.), Oken, E. (Emily), Page, C. M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Goran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Raikkonen, K. (Katri), Reese, S. E. (Sarah E.), Reischl, E. (Eva), Richiardi, L. (Lorenzo), Ring, S. (Susan), Roy, R. P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D. A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sorensen, T. I. (Thorkild I. A.), Starling, A. P. (Anne P.), Sunyer, J. (Jordi), ATaylor, J. (Jack), Tiemeier, H. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), Van Ijzendoorn, M. H. (Marinus H.), Vonk, J. M. (Judith M.), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. L. (Joseph L.), Wilcox, A. J. (Allen J.), Wright, R. J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I. V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C. L. (Caroline L.), Jaddoe, V. W. (Vincent W. V.), London, S. J. (Stephanie J.), Felix, J. F. (Janine F.), Joubert, B. R. (Bonnie R.), Baccarelli, A. A. (Andrea A.), Sharp, G. C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baiz, N. (Nour), Bakermans-Kranenburg, M. J. (Marian J.), Bakulski, K. M. (Kelly M.), Binder, E. B. (Elisabeth B.), Bouchard, L. (Luigi), Breton, C. V. (Carrie V.), Brunekreef, B. (Bert), Brunst, K. J. (Kelly J.), Burchard, E. G. (Esteban G.), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M. C. (Monica Cheng), Corpeleijn, E. (Eva), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G. D. (George Davey), De Boever, P. (Patrick), Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (Brenda), Everson, T. M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M. D. (M. Daniele), Farchi, S. (Sara), Fernandez, M. F. (Mariana F.), Gao, L. (Lu), Gaunt, T. R. (Tom R.), Ghantous, A. (Akram), Gillman, M. W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Haberg, S. E. (Siri E.), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J. W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D. D. (Dereje D.), Just, A. C. (Allan C.), Karagas, M. R. (Margaret R.), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K. J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G. H. (Gerard H.), Kupers, L. K. (Leanne K.), Ladd-Acosta, C. (Christine), Lahti, J. (Jari), Lambrechts, N. (Nathalie), Langie, S. A. (Sabine A. S.), Lie, R. T. (Rolv T.), Liu, A. H. (Andrew H.), Magnus, M. C. (Maria C.), Magnus, P. (Per), Maguire, R. L. (Rachel L.), Marsit, C. J. (Carmen J.), McArdle, W. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S. K. (Susan K.), Nawrot, T. S. (Tim S.), Nistico, L. (Lorenza), Nohr, E. A. (Ellen A.), Nordlund, B. (Bjorn), Nystad, W. (Wenche), Oh, S. S. (Sam S.), Oken, E. (Emily), Page, C. M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Goran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Raikkonen, K. (Katri), Reese, S. E. (Sarah E.), Reischl, E. (Eva), Richiardi, L. (Lorenzo), Ring, S. (Susan), Roy, R. P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D. A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sorensen, T. I. (Thorkild I. A.), Starling, A. P. (Anne P.), Sunyer, J. (Jordi), ATaylor, J. (Jack), Tiemeier, H. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), Van Ijzendoorn, M. H. (Marinus H.), Vonk, J. M. (Judith M.), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. L. (Joseph L.), Wilcox, A. J. (Allen J.), Wright, R. J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I. V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C. L. (Caroline L.), Jaddoe, V. W. (Vincent W. V.), and London, S. J. (Stephanie J.)
Published: 2018

25. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author: Felix, Janine, Joubert, BR, Baccarelli, AA, Sharp, GC, Almqvist, C, Annesi-Maesano, I, Arshad, H, Baiz, N, Bakermans-Kranenburg, MJ, Bakulski, KM, Binder, EB, Bouchard, L, Breton, CV, Brunekreef, B, Brunst, KJ, Burchard, EG, Bustamante, M, Chatzi, L, Munthe-Kaas, MC, Corpeleijn, E, Czamara, D, Dabelea, D, Smith, GD, De Boever, P, Duijts, Liesbeth, Dwyer, T, Eng, C, Eskenazi, B, Everson, TM, Falahi, F, Fallin, MD, Farchi, S, Fernandez, MF, Gao, L, Gaunt, TR, Ghantous, A, Gillman, MW, Gonseth, S, Grote, V, Gruzieva, O, Haberg, SE, Herceg, Z, Hivert, MF, Holland, N, Holloway, JW, Hoyo, C, Hu, DL, Huang, RC, Huen, K, Jarvelin, MR, Jima, DD, Just, AC, Karagas, MR, Karlsson, R, Karmaus, W, Kechris, KJ, Kere, J, Kogevinas, M, Koletzko, B, Koppelman, GH, Kupers, LK, Ladd-Acosta, C, Lahti, J, Lambrechts, N, Langie, SAS, Lie, RT, Liu, AH, Magnus, MC, Magnus, P, Maguire, RL, Marsit, CJ, McArdle, W, Melen, E, Melton, P, Murphy, SK, Nawrot, TS, Nistico, L, Nohr, EA, Nordlund, B, Nystad, W, Oh, SS, Oken, E, Page, CM, Perron, P, Pershagen, G, Pizzi, C, Plusquin, M, Raikkonen, K, Reese, SE, Reischl, E, Richiardi, L, Ring, S, Roy, RP, Rzehak, P, Schoeters, G, Schwartz, DA, Sebert, S, Snieder, H, Sorensen, TIA, Starling, AP, Sunyer, J, Ataylor, J, Tiemeier, Henning, Ullemar, V, Vafeiadi, M, van IJzendoorn, Marinus, Vonk, JM, Vriens, A, Vrijheid, M, Wang, P, Wiemels, JL, Wilcox, AJ, Wright, RJ, Xu, CJ, Xu, ZL, Yang, IV, Yousefi, P, Zhang, HM, Zhang, WM, Zhao, SS, Agha, G, Relton, CL, Jaddoe, Vincent, London, SJ, Felix, Janine, Joubert, BR, Baccarelli, AA, Sharp, GC, Almqvist, C, Annesi-Maesano, I, Arshad, H, Baiz, N, Bakermans-Kranenburg, MJ, Bakulski, KM, Binder, EB, Bouchard, L, Breton, CV, Brunekreef, B, Brunst, KJ, Burchard, EG, Bustamante, M, Chatzi, L, Munthe-Kaas, MC, Corpeleijn, E, Czamara, D, Dabelea, D, Smith, GD, De Boever, P, Duijts, Liesbeth, Dwyer, T, Eng, C, Eskenazi, B, Everson, TM, Falahi, F, Fallin, MD, Farchi, S, Fernandez, MF, Gao, L, Gaunt, TR, Ghantous, A, Gillman, MW, Gonseth, S, Grote, V, Gruzieva, O, Haberg, SE, Herceg, Z, Hivert, MF, Holland, N, Holloway, JW, Hoyo, C, Hu, DL, Huang, RC, Huen, K, Jarvelin, MR, Jima, DD, Just, AC, Karagas, MR, Karlsson, R, Karmaus, W, Kechris, KJ, Kere, J, Kogevinas, M, Koletzko, B, Koppelman, GH, Kupers, LK, Ladd-Acosta, C, Lahti, J, Lambrechts, N, Langie, SAS, Lie, RT, Liu, AH, Magnus, MC, Magnus, P, Maguire, RL, Marsit, CJ, McArdle, W, Melen, E, Melton, P, Murphy, SK, Nawrot, TS, Nistico, L, Nohr, EA, Nordlund, B, Nystad, W, Oh, SS, Oken, E, Page, CM, Perron, P, Pershagen, G, Pizzi, C, Plusquin, M, Raikkonen, K, Reese, SE, Reischl, E, Richiardi, L, Ring, S, Roy, RP, Rzehak, P, Schoeters, G, Schwartz, DA, Sebert, S, Snieder, H, Sorensen, TIA, Starling, AP, Sunyer, J, Ataylor, J, Tiemeier, Henning, Ullemar, V, Vafeiadi, M, van IJzendoorn, Marinus, Vonk, JM, Vriens, A, Vrijheid, M, Wang, P, Wiemels, JL, Wilcox, AJ, Wright, RJ, Xu, CJ, Xu, ZL, Yang, IV, Yousefi, P, Zhang, HM, Zhang, WM, Zhao, SS, Agha, G, Relton, CL, Jaddoe, Vincent, and London, SJ
Published: 2018

26. Peripheral blood mitochondrial DNA content in relation to circulating metabolites and inflammatory markers: A population study

Author: Knez J, Marrachelli V, Cauwenberghs N, Winckelmans E, Zhang Z, Thijs L, Brguljan-Hitij J, Plusquin M, Delles C, Monleon D, Redon J, Staessen J, Nawrot T, and Kuznetsova T
Published: 2017

27. Stem cell activity and oxidative stress as response to cadmium and hexavalent chromium in M. lignano

Author: Plusquin, M., Smeets, K., Geerdens, E., Cuypers, A., and Artois, T.
Subjects: Macrostomum lignano
Published: 2009

28. Risk of Cancer and Environmental Exposure to Cadmium in a Prospective Population Study

Author: Nawrot, T, primary, Plusquin, M, additional, Hogervorst, J, additional, Roels, H, additional, Celis, H, additional, Thijs, L, additional, Vangronsveld, J, additional, Van Hecke, E, additional, and Staessen, J A., additional
Published: 2006
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29. The multi-omics signatures of telomere length in childhood.

Author: Wang C, Martens DS, Bustamante M, Alfano R, Plusquin M, Maitre L, Wright J, McEachan RRC, Lepeule J, Slama R, Vafeiadi M, Chatzi L, Grazuleviciene R, Gutzkow KB, Keun H, Borràs E, Sabidó E, Carracedo A, Escarami G, Anguita-Ruiz A, Pelegrí-Sisó D, Gonzalez JR, Vrijheid M, and Nawrot TS
Subjects: Humans, Child, Female, Male, Telomere Homeostasis genetics, Body Mass Index, CpG Islands, Genomics methods, MicroRNAs genetics, Multiomics, Telomere genetics, Telomere metabolism, DNA Methylation
Abstract: Background: Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length., Methods: This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated., Results: After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways., Conclusions: Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging., Competing Interests: Declarations. Ethics approval and consent to participate: The HELIX study complies with the Declaration of Helsinki. All six cohorts existed for several years before HELIX started, and had undergone the required evaluation by national ethics committees: EDEN received approval from the ethics committee (CCPPRB) of Kremlin Bicêtre and from CNIL (Commission Nationale Informatique et Liberté), the French data privacy institution; BiB received ethics approval from the Bradford Research Ethics Committee; INMA obtained the approval of the ethics committee of each involved hospital or health center; the research protocol of KANC was approved by the Lithuanian Bioethics Committee; MoBa received approval from a Norwegian regional committee for medical and health research ethics; and the ethics committee of the university hospital at Heraklion approved the study protocols of RHEA. An informed consent has been signed by all participants at recruitment and at the follow-up visit for clinical examinations and biospecimen collection. Each cohort also confirmed that relevant informed consent and approval were in place for the secondary use of data from pre-existing data. The work in HELIX was covered by new ethics approvals in each country. The HELIX project received ethical approvals from the Comité Ético de investigación Clínica Parc de Salut MAR. At follow-up enrolment in the HELIX subcohort and panel studies, participants were asked to sign an informed consent for clinical examination and biospecimen collection and analysis. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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30. Prenatal ambient temperature exposure and cord blood and placental mitochondrial DNA content: Insights from the ENVIRONAGE birth cohort study.

Author: Renaers E, Wang C, Bijnens EM, Plusquin M, Nawrot TS, and Martens DS
Abstract: Background: Mitochondrial DNA content (mtDNAc) at birth is a sensitive biomarker to environmental exposures that may play an important role in later life health. We investigated sensitive time windows for the association between prenatal ambient temperature exposure and newborn mtDNAc., Methods: In the ENVIRONAGE birth cohort (Belgium), we measured cord blood and placental mtDNAc in 911 participants using a quantitative real-time polymerase chain reaction. We associated newborn mtDNAc with average weekly mean temperature during pregnancy using distributed lag nonlinear models (DLNMs). Double-threshold DLNMs were used to study the relationships between ambient temperature and mtDNAc below predefined low (5th, 10th, 15th percentile of the temperature distribution) and above predefined high temperature thresholds (95th, 90th, 85th percentile of the temperature distribution)., Findings: Prenatal temperature exposure above the used high temperature thresholds was linked to lower cord blood mtDNAc, with the strongest effect in trimester 2 (cumulative estimates ranging from -21.4% to -25.6%). Placental mtDNAc showed positive and negative associations for high temperature exposure depending on the applied high temperature threshold. Negative associations were observed during trimester 1 using the 90th and 95th percentile threshold (-26.1% and -33.2% lower mtDNAc respectively), and a positive association in trimester 3 when applying the most stringent 95th percentile threshold (127.0%). Low temperature exposure was associated with higher mtDNAc for both cord blood and placenta. Cord blood mtDNAc showed a positive association in trimester 2 when using the 10th percentile threshold (11.3%), while placental mtDNAc showed positive associations during the whole gestation and for all applied thresholds (estimates ranging from 80.8% - 320.6%)., Interpretation: Our study shows that in utero temperature exposure is associated with differences in newborn mtDNAc at birth, with stronger associations observed in the placenta. These findings highlight the impact of prenatal ambient temperature exposure on mtDNAc during pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2025
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31. Alterations in the placental proteome in association with the presence of black carbon particles: A discovery study.

Author: Millen JL, Luyten LJ, Dieu M, Bové H, Ameloot M, Bongaerts E, Demazy C, Fransolet M, Martens DS, Renard P, Reimann B, Plusquin M, Nawrot TS, and Debacq-Chainiaux F
Subjects: Humans, Female, Pregnancy, Adult, Air Pollutants toxicity, Air Pollutants analysis, Maternal Exposure adverse effects, Particulate Matter analysis, Particulate Matter toxicity, Cohort Studies, Placenta metabolism, Placenta chemistry, Proteome, Soot
Abstract: Background: Exposure to ambient air pollution is known to cause direct and indirect molecular expression changes in the placenta, on the DNA, mRNA, and protein levels. Ambient black carbon (BC) particles can be found in the human placenta already very early in gestation. However, the effect of in utero BC exposure on the entire placental proteome has never been studied to date., Objectives: We explored whether placental proteome differs between mothers exposed to either high or low BC levels throughout the entire pregnancy., Methods: We used placental tissue samples from the ENVIRONAGE birth cohort, of 20 non-smoking, maternal- and neonate characteristic-matched women exposed to high (n = 10) or low (n = 10) levels of ambient BC throughout pregnancy. We modeled prenatal BC exposure levels based on the mother's home address and measured BC levels in the fetal side of the placenta. The placental proteome was analyzed by nano-liquid chromatography Q-TOF mass spectrometry. PEAKS software was used for protein identification and label-free quantification. Protein-protein interaction and functional pathway enrichment analyses were performed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software., Results: The accumulation of BC particles in placenta was 2.19 times higher in the high versus low exposure group (20943.4 vs 9542.7 particles/mm³; p = 0.007). Thirteen proteins showed a ≥2-fold expression difference between the two exposure groups, all overexpressed in the placentas of women prenatally exposed to high BC levels. Three protein-protein interactions were enriched within this group, namely between TIMP3 and COL4A2, SERPINE2 and COL4A2, and SERPINE2 and GP1BB. Functional pathway enrichment analysis put forward pathways involved in extracellular matrix-receptor interaction, fibrin clot formation, and sodium ion transport regulation., Discussion: Prenatal BC exposure affects the placental proteome. Future research should focus on the potential consequences of these alterations on placental functioning, and health and disease during early childhood development., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tim S. Nawrot, Marcel Ameloot and Hannelore Bové have the patent "Method for detecting or quantifying carbon black and/or black carbon particles" issued to Katholieke Universiteit Leuven, Universiteit Hasselt. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
Published: 2024
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32. Impact on murine neurodevelopment of early-life exposure to airborne ultrafine carbon nanoparticles.

Author: Vanbrabant K, Rasking L, Vangeneugden M, Bové H, Ameloot M, Vanmierlo T, Schins RPF, Cassee FR, and Plusquin M
Subjects: Animals, Pregnancy, Female, Male, Inhalation Exposure adverse effects, Air Pollutants toxicity, Mice, Maternal Exposure adverse effects, Anxiety chemically induced, Prenatal Exposure Delayed Effects chemically induced, Mice, Inbred C57BL, Nanoparticles toxicity, Particulate Matter toxicity, Carbon toxicity, Behavior, Animal drug effects, Particle Size
Abstract: The effects of ultrafine particle (UFP) inhalation on neurodevelopment, especially during critical windows of early life, remain largely unexplored. The specific time windows during which exposure to UFP might be the most detrimental remain poorly understood. Here, we studied early-life exposure to clean ultrafine carbonaceous particles (UFP C ) and neurodevelopment and central nervous system function in offspring.Pregnant wild-type C57BL/6J mice were either sham-exposed (HEPA-filtered air) or exposed to clean ultrafine carbonaceous particles at a concentration of 438 ± 72 μg/m³ (mean ± SD) and a count median diameter of 49 ± 2 nm (CMD ± GSD) via whole-body exposure for four hours per day. For prenatal exposure, mice were exposed for two consecutive days in two exposure periods, while the postnatal exposure was conducted for four consecutive days in two exposure periods. The mice were divided into four groups: (i) sham, (ii) only prenatal exposure, (iii) only postnatal exposure, and (iv) both prenatal and postnatal exposure. Neurodevelopmental behaviour was assessed throughout the life of the offspring using a functional observation battery.Early-life UFP C -exposed offspring exhibited altered anxiety-related behaviour in the open field test, with exclusively postnatally exposed offspring (567 ± 120 s) spending significantly more time within the border zone of the arena compared to the sham group (402 ± 73 s), corresponding to an increase of approximately 41% (p < 0.05). The behavioural alterations remained unaffected by olfactory function or maternal behaviour. Mice with both prenatal and postnatal exposure did not show this effect. No discernible impact on developmental behavioural reflexes was evident.Early life exposure to UFP C , particularly during the early postnatal period, may lead to developmental neurotoxicity, potentially resulting in complications for the central nervous system later in life. The current data will support future studies investigating the possible effects and characteristics of nanoparticle-based toxicity., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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33. Translocation of black carbon particles to human intestinal tissue.

Author: Van Pee T, Vanbrabant K, Rasking L, Van Eyken P, Hogervorst J, Caenepeel P, Ameloot M, Plusquin M, and Nawrot TS
Subjects: Humans, Male, Aged, Female, Particulate Matter, Aged, 80 and over, Biopsy, Ileum metabolism, Carbon metabolism, Colon metabolism, Tissue Distribution, Soot, Intestinal Mucosa metabolism
Abstract: Background: Evidence is accumulating that elevated levels of particulate air pollution, including black carbon, have been linked to gastrointestinal disorders and a lower intestinal bacterial richness and diversity. One of the hypothesized underlying mechanisms is the absorption of air pollution-related particles from the gastrointestinal tract., Methods: We visualized and quantified black carbon particles via white light generation under femtosecond-pulsed laser illumination in ileum and colon biopsies of five human patients. The biodistribution was assessed in three different layers (i.e., mucosa, submucosa, and muscularis propria)., Findings: Black carbon particles could be identified in all three tissue layers of the ileum and colon biopsies of five participants (two men and three women; mean ± standard deviation age, 76.40 ± 7.37 years), and their carbonaceous nature was confirmed via emission fingerprinting. The median (±SD) black carbon load was borderline statistically significantly higher in the ileum compared to the colon (1.21 × 10 5 ± 1.68 × 10 4 particles/mm 3 versus 9.34 × 10 4 ± 1.33 × 10 4 particles/mm 3 ; p = 0.07) and was driven by a difference in black carbon load in the submucosa layer (p = 0.01). Regarding the three tissue layers, loads were higher in the submucosa, compared with the mucosa (ileum: +76%, p < 0.0001; colon: +70%, p = 0.0001) and muscularis propria (ileum: +88%, p < 0.0001; colon: +88%, p < 0.0001). In ileum, loads were borderline higher in the mucosa versus muscularis propria (p = 0.09)., Interpretation: This explorative study provides real-life evidence that black carbon particles can reach the intestinal tissue and accumulate in different intestinal tissue layers. These findings support further research into how particulate air pollution directly affects gastrointestinal health., Funding: Thessa Van Pee holds a doctoral fellowship from the Research Foundation Flanders (FWO), grant number: 11C7421N. Tim Nawrot is a Methusalem grant holder., Competing Interests: Declaration of interests MA and TSN declare that aspects of the work mentioned in the paper are the subject of an awarded patent (Method for detecting or quantifying carbon black and/or black carbon particles, reference codes: EP3403068B1 and US11002679B2) filed by Hasselt University (Hasselt, Belgium) and KU Leuven (Leuven, Belgium). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Published: 2024
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34. Newborn glomerular function and gestational particulate air pollution.

Author: Rasking L, Van Pee T, Vangeneugden M, Renaers E, Wang C, Penders J, De Vusser K, Plusquin M, and Nawrot TS
Subjects: Humans, Female, Pregnancy, Infant, Newborn, Adult, Maternal Exposure adverse effects, Kidney Glomerulus, Male, Belgium epidemiology, Biomarkers, Glomerular Filtration Rate, Particulate Matter adverse effects, Particulate Matter analysis, Cystatin C blood, Air Pollution adverse effects, Air Pollution analysis, Fetal Blood
Abstract: Background: Nephron number variability may hold significance in the Developmental Origins of Health and Disease hypothesis. We explore the impact of gestational particulate pollution exposure on cord blood cystatin C, a marker for glomerular function, as an indicator for glomerular health at birth., Methods: From February 2010 onwards, the ENVIRONAGE cohort includes over 2200 mothers giving birth at the East-Limburg hospital in Genk, Belgium. Mothers without planned caesarean section who are able to fill out a Dutch questionnaire are eligible. Here, we evaluated cord blood cystatin C levels from 1484 mother-child pairs participating in the ENVIRONAGE cohort. We employed multiple linear regression models and distributed lag models to assess the association between cord blood cystatin C and gestational particulate air pollution exposure., Findings: Average ± SD levels of cord blood cystatin C levels amounted to 2.16 ± 0.35 mg/L. Adjusting for covariates, every 0.5 μg/m³ and 5 μg/m³ increment in gestational exposure to black carbon (BC) and fine particulate matter (PM 2.5 ) corresponded to increases of 0.04 mg/L (95% CI 0.01-0.07) and 0.07 mg/L (95% CI 0.03-0.11) in cord blood cystatin C levels (p < 0.01), respectively. Third-trimester exposure showed similar associations, with a 0.04 mg/L (95% CI 0.00-0.08) and 0.06 mg/L (95% CI 0.04-0.09) increase for BC and PM 2.5 (p < 0.02). No significant associations were observed when considering only the first and second trimester exposure., Interpretation: Our findings indicate that particulate air pollution during the entire pregnancy, with the strongest effect sizes from week 27 onwards, may affect newborn kidney function, with potential long-term implications for later health., Funding: Special Research Fund (Bijzonder Onderzoeksfonds, BOF), Flemish Scientific Research Fund (Fonds Wetenschappelijk Onderzoek, FWO), and Methusalem., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Published: 2024
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35. Quantification of ADHD medication in biological fluids of pregnant and breastfeeding women with liquid chromatography: a comprehensive review.

Author: De Hondt L, Cosemans C, Plusquin M, Mangelings D, Van Eeckhaut A, and Tommelein E
Subjects: Humans, Female, Pregnancy, Chromatography, Liquid, Adult, Methylphenidate therapeutic use, Attention Deficit Disorder with Hyperactivity drug therapy, Milk, Human chemistry, Breast Feeding
Abstract: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that has long been considered a concern only in the pediatric population. However, symptoms often sustain into adulthood and may require medication. For women with ADHD, this also means dealing with the disorder during the reproductive period. Medication safety during pregnancy and breastfeeding is a critical concern, and the potential transfer of ADHD medication to infants remains a topic of scientific interest. The quantification of ADHD medications in both maternal blood and breast milk are vital for understanding their pharmacokinetics and potential exposure risks for (nursing) infants. This review aims (1) to compile and critically assess existing research on the transfer of ADHD medications into breast milk and the potential implications for nursing infants and (2) to provide a comprehensive overview and discussion of the literature regarding the quantification of methylphenidate, amphetamine, atomoxetine, viloxazine, guanfacine, clonidine and bupropion in the blood, urine, oral fluid, and breast milk with liquid chromatography. A literature search was conducted using PubMed, Scopus, and Web of Science, to identify relevant articles published from January 2014 up to December 2023. We illustrate the lack of methods to simultaneously monitor multiple ADHD medications as well as the lack of developed methods for breast milk. Finally, we highlight the need for continued research to refine our understanding of medication transfer into breast milk and potential risks, and to develop clinical guidelines to support mothers with ADHD in making informed choices regarding medication use during pregnancy and lactation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 De Hondt, Cosemans, Plusquin, Mangelings, Van Eeckhaut and Tommelein.)
Published: 2024
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36. Prenatal particulate matter exposure is linked with neurobehavioural development in early life.

Author: Cosemans C, Madhloum N, Sleurs H, Alfano R, Verheyen L, Wang C, Vanbrabant K, Vanpoucke C, Lefebvre W, Nawrot TS, and Plusquin M
Subjects: Humans, Female, Pregnancy, Child, Preschool, Male, Infant, Newborn, Infant, Air Pollutants toxicity, Air Pollutants analysis, Child Development drug effects, Child, Maternal Exposure adverse effects, Longitudinal Studies, Adult, Child Behavior drug effects, Particulate Matter toxicity, Particulate Matter analysis, Prenatal Exposure Delayed Effects chemically induced
Abstract: Background: Early life exposure to ambient particulate matter (PM) may negatively affect neurobehavioral development in children, influencing their cognitive, emotional, and social functioning. Here, we report a study on prenatal PM 2.5 exposure and neurobehavioral development focusing on different time points in the first years of life., Methods: This study was part of the ENVIRONAGE birth cohort that follows mother-child pairs longitudinally. First, the Neonatal Behavioral Assessment Scale (NBAS) was employed on 88 newborns aged one to two months to assess their autonomic/physiological regulation, motor organisation, state organisation/regulation, and attention/social interaction. Second, our study included 393 children between the ages of four and six years, for which the Strengths and Difficulties Questionnaire (SDQ) was used to assess the children's emotional problems, hyperactivity, conduct problems, peer relationship, and prosocial behaviour. Prenatal PM 2.5 exposure was determined using a high-resolution spatial-temporal method based on the maternal address. Multiple linear and multinomial logistic regression models were used to analyse the relationship between prenatal PM 2.5 exposure and neurobehavioral development in newborns and children, respectively., Results: A 5 μg/m³ increase in first-trimester PM 2.5 concentration was associated with lower NBAS range of state cluster scores (-6.11%; 95%CI: -12.00 to -0.23%; p = 0.04) in one-to-two-month-old newborns. No other behavioural clusters nor the reflexes cluster were found to be associated with prenatal PM 2.5 exposure. Furthermore, a 5 μg/m³ increment in first-trimester PM 2.5 levels was linked with higher odds of a child experiencing peer problems (Odds Ratio (OR) = 3.89; 95%CI: 1.39 to 10.87; p = 0.01) at ages four to six. Additionally, a 5 μg/m³ increase in second-trimester PM 2.5 concentration was linked to abnormal prosocial behaviour (OR = 0.49; 95%CI: 0.25 to 0.98; p = 0.04) at four to six years old. No associations were found between in utero PM 2.5 exposure and hyperactivity or conduct problems., Conclusions: Our findings suggest that prenatal exposure to PM may impact neurobehavioural development in newborns and preschool children. We identified sensitive time windows during early-to-mid pregnancy, possibly impacting stage changes in newborns and peer problems and prosocial behaviour in children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tim S Nawrot reports financial support was provided by the European Research Council, Research Foundation Flanders, Kom op Tegen Kanker, and the Methusalem Fund. Kenneth Vanbrabant reports financial support was provided by Research Foundation Flanders. Charlotte Cosemans reports financial support was provided by the Special Research Fund of Hasselt University and Fund Orcadia, managed by the King Baudouin Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)
Published: 2024
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37. Telomere length in early childhood and its association with attention: a study in 4-6 year old children.

Author: Croons H, Martens DS, Vanderstukken C, Sleurs H, Rasking L, Peusens M, Renaers E, Plusquin M, and Nawrot TS
Abstract: Telomere length (TL), a marker of cellular aging, has been studied in adults with regard to its connection to cognitive function. However, little is known about the association between TL and cognitive development in children. This study investigated the interplay between TL and cognitive functioning in 283 Belgian children aged four to six years of the Environmental Influence on Aging in Early Life (ENVIR ON AGE) birth cohort. Child leukocyte TL was measured using qPCR, while cognitive functioning, including attention and memory, was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear regression models were employed to examine the association between TL and cognitive outcomes, adjusting for potential confounders. We found an inverse association between TL and the spatial errors made during the Motor Screening task ( p = 0.017), indicating a higher motor accuracy in children with longer telomeres. No significant associations were found between TL and other cognitive outcomes. Our results suggest a specific link between TL and motor accuracy but not with the other cognitive domains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Croons, Martens, Vanderstukken, Sleurs, Rasking, Peusens, Renaers, Plusquin and Nawrot.)
Published: 2024
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38. Green space exposure and blood DNA methylation at birth and in childhood - A multi-cohort study.

Author: Aguilar-Lacasaña S, Fontes Marques I, de Castro M, Dadvand P, Escribà X, Fossati S, González JR, Nieuwenhuijsen M, Alfano R, Annesi-Maesano I, Brescianini S, Burrows K, Calas L, Elhakeem A, Heude B, Hough A, Isaevska E, W V Jaddoe V, Lawlor DA, Monaghan G, Nawrot T, Plusquin M, Richiardi L, Watmuff A, Yang TC, Vrijheid M, F Felix J, and Bustamante M
Subjects: Humans, Female, Pregnancy, Infant, Newborn, Cohort Studies, Male, Fetal Blood chemistry, Child, Birth Cohort, DNA Methylation, Environmental Exposure
Abstract: Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the association between green space exposure and cord and child blood DNA methylation. Data from eight European birth cohorts with a total of 2,988 newborns and 1,849 children were used. Two indicators of residential green space exposure were assessed: (i) surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m and 300 m) and (ii) proximity to green space (having a green space ≥ 5,000 m 2 within a distance of 300 m). For these indicators we assessed two exposure windows: (i) pregnancy, and (ii) the period from pregnancy to child blood DNA methylation assessment, named as cumulative exposure. DNA methylation was measured with the Illumina 450K or EPIC arrays. To identify differentially methylated positions (DMPs) we fitted robust linear regression models between pregnancy green space exposure and cord blood DNA methylation and between cumulative green space exposure and child blood DNA methylation. Two sensitivity analyses were conducted: (i) without adjusting for cellular composition, and (ii) adjusting for air pollution. Cohort results were combined through fixed-effect inverse variance weighted meta-analyses. Differentially methylated regions (DMRs) were identified from meta-analysed results using the Enmix-combp and DMRcate methods. There was no statistical evidence of pregnancy or cumulative exposures associating with any DMP (False Discovery Rate, FDR, p-value < 0.05). However, surrounding greenness exposure was inversely associated with four DMRs (three in cord blood and one in child blood) annotated to ADAMTS2, KCNQ1DN, SLC6A12 and SDK1 genes. Results did not change substantially in the sensitivity analyses. Overall, we found little evidence of the association between green space exposure and blood DNA methylation. Although we identified associations between surrounding greenness exposure with four DMRs, these findings require replication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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39. Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories.

Author: Van Pee T, Martens DS, Alfano R, Engelen L, Sleurs H, Rasking L, Plusquin M, and Nawrot TS
Subjects: Humans, Female, Male, Infant, Newborn, Child, Preschool, Proteomics methods, Child, Belgium, Infant, Prospective Studies, Proteome analysis, Proteome metabolism, Adult, Child Development physiology, Cohort Studies, Fetal Blood chemistry, Fetal Blood metabolism, Birth Weight physiology
Abstract: Importance: The cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored., Objective: To identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories., Design, Setting, and Participants: This cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023., Main Outcomes and Measures: The outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins., Results: The sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, -237.52 [95% CI, -343.15 to -131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, -342.78 [95% CI, -463.10 to -222.47]; BWR: coefficient, -0.11 [95% CI, -0.14 to -0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, -366.32 [95% CI, -476.66 to -255.97]; BWR: coefficient, -0.11 [95% CI, -0.15 to -0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, -208.75 [95% CI, -305.23 to -112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, -209.27 [95% CI, -295.14 to -123.40]; BWR: coefficient, -0.07 [95% CI, -0.09 to -0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, -1.33 to -0.68 kg) and body mass index z score (coefficients, -0.41 to -0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, -1.98 to -0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight., Conclusions and Relevance: This cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics.
Published: 2024
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40. Accumulation of Ambient Black Carbon Particles Within Key Memory-Related Brain Regions.

Author: Vanbrabant K, Van Dam D, Bongaerts E, Vermeiren Y, Bové H, Hellings N, Ameloot M, Plusquin M, De Deyn PP, and Nawrot TS
Subjects: Adult, Female, Humans, Aged, 80 and over, Tissue Distribution, Cognition, Carbon, Brain, Alzheimer Disease
Abstract: Importance: Ambient air pollution is a worldwide problem, not only related to respiratory and cardiovascular diseases but also to neurodegenerative disorders. Different pathways on how air pollutants could affect the brain are already known, but direct evidence of the presence of ambient particles (or nanoparticles) in the human adult brain is limited., Objective: To examine whether ambient black carbon particles can translocate to the brain and observe their biodistribution within the different brain regions., Design, Setting, and Participants: In this case series a label-free and biocompatible detection technique of nonincandescence-related white light generation was used to screen different regions of biobanked brains of 4 individuals from Belgium with neuropathologically confirmed Alzheimer disease for the presence of black carbon particles. The selected biological specimens were acquired and subsequently stored in a biorepository between April 2013 and April 2017. Black carbon measurements and data analysis were conducted between June 2020 and December 2022., Main Outcomes and Measures: The black carbon load was measured in various human brain regions. A Kruskal-Wallis test was used to compare black carbon loads across these regions, followed by Dunn multiple comparison tests., Results: Black carbon particles were directly visualized in the human brain of 4 individuals (3 women [75%]; mean [SD] age, 86 [13] years). Screening of the postmortem brain regions showed a significantly higher median (IQR) number of black carbon particles present in the thalamus (433.6 [289.5-540.2] particles per mm3), the prefrontal cortex including the olfactory bulb (420.8 [306.6-486.8] particles per mm3), and the hippocampus (364.7 [342.0-448.7] particles per mm3) compared with the cingulate cortex (192.3 [164.2-277.5] particles per mm3), amygdala (217.5 [147.3-244.5] particles per mm3), and the superior temporal gyrus (204.9 [167.9-236.8] particles per mm3)., Conclusions and Relevance: This case series provides evidence that ambient air pollution particles are able to translocate to the human brain and accumulate in multiple brain regions involved in cognitive functioning. This phenomenon may contribute to the onset and development of neurodegenerative disorders.
Published: 2024
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41. Black carbon particles in human breast milk: assessing infant's exposure.

Author: Cosemans C, Bongaerts E, Vanbrabant K, Reimann B, Silva AI, Tommelein E, Poma G, Ameloot M, Nawrot TS, and Plusquin M
Subjects: Infant, Female, Humans, Nitrogen Dioxide, Pilot Projects, Milk, Human chemistry, Environmental Exposure adverse effects, Particulate Matter analysis, Carbon, Air Pollutants analysis
Abstract: Background/aim: Human breast milk is the recommended source of nutrition for infants due to its complex composition and numerous benefits, including a decline in infection rates in childhood and a lower risk of obesity. Hence, it is crucial that environmental pollutants in human breast milk are minimized. Exposure to black carbon (BC) particles has adverse effects on health; therefore, this pilot study investigates the presence of these particles in human breast milk., Methods: BC particles from ambient exposure were measured in eight human breast milk samples using a white light generation under femtosecond illumination. The carbonaceous nature of the particles was confirmed with BC fingerprinting. Ambient air pollution exposures (PM 2.5 , PM 10 , and NO 2 ) were estimated using a spatial interpolation model based on the maternal residential address. Spearman rank correlation coefficients were obtained to assess the association between human breast milk's BC load and ambient air pollution exposure., Results: BC particles were found in all human breast milk samples. BC loads in human breast milk were strongly and positively correlated with recent (i.e., 1 week) maternal residential NO 2 ( r = 0.79; p = 0.02) exposure and medium-term (i.e., 1 month) PM 2.5 ( r = 0.83; p = 0.02) and PM 10 ( r = 0.93; p = 0.002) exposure., Conclusion: For the first time, we showed the presence of BC particles in human breast milk and found a robust association with ambient air pollution concentrations. Our findings present a pioneering insight into a novel pathway through which combustion-derived air pollution particles can permeate the delicate system of infants., Competing Interests: MA and TN declare that aspects of the work are subject of a patent application (method for detecting or quantifying carbon black and/or black carbon particles, US20190025215A1) filed by Hasselt University (Hasselt, Belgium) and KU Leuven (Leuven, Belgium). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cosemans, Bongaerts, Vanbrabant, Reimann, Silva, Tommelein, Poma, Ameloot, Nawrot and Plusquin.)
Published: 2024
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42. A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.

Author: Li S, Spitz N, Ghantous A, Abrishamcar S, Reimann B, Marques I, Silver MJ, Aguilar-Lacasaña S, Kitaba N, Rezwan FI, Röder S, Sirignano L, Tuhkanen J, Mancano G, Sharp GC, Metayer C, Morimoto L, Stein DJ, Zar HJ, Alfano R, Nawrot T, Wang C, Kajantie E, Keikkala E, Mustaniemi S, Ronkainen J, Sebert S, Silva W, Vääräsmäki M, Jaddoe VWV, Bernstein RM, Prentice AM, Cosin-Tomas M, Dwyer T, Håberg SE, Herceg Z, Magnus MC, Munthe-Kaas MC, Page CM, Völker M, Gilles M, Send T, Witt S, Zillich L, Gagliardi L, Richiardi L, Czamara D, Räikkönen K, Chatzi L, Vafeiadi M, Arshad SH, Ewart S, Plusquin M, Felix JF, Moore SE, Vrijheid M, Holloway JW, Karmaus W, Herberth G, Zenclussen A, Streit F, Lahti J, Hüls A, Hoang TT, London SJ, and Wiemels JL
Subjects: Child, Female, Humans, Infant, Newborn, Pregnancy, Epigenesis, Genetic, Epigenomics, Birth Order, DNA Methylation
Abstract: Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends., (© 2024. The Author(s).)
Published: 2024
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43. Exposure to Residential Green Space and Bone Mineral Density in Young Children.

Author: Sleurs H, Silva AI, Bijnens EM, Dockx Y, Peusens M, Rasking L, Plusquin M, and Nawrot TS
Subjects: Infant, Newborn, Male, Humans, Female, Child, Preschool, Cohort Studies, Parks, Recreational, Prospective Studies, Bone Density, Fractures, Bone
Abstract: Importance: Bone mass accrual is influenced by environmental and lifestyle factors. Targeted interventions at the early stages of life might decrease fracture and/or osteoporosis risk later in life., Objective: To investigate whether early-life exposure to residential surrounding green space is associated with a change in bone mineral density in young children., Design, Setting, and Participants: In this prospective birth cohort study (ENVIRONAGE [Environmental Influence on Aging in Early Life]), mother-child pairs from Flanders, Belgium, were recruited at birth and followed up for 4 to 6 years, between October 1, 2014, and July 31, 2021. Data analysis was conducted between January and February 2022., Exposures: Green space was estimated for high green (>3 m vegetation height), low green (≤3 m vegetation height ), and total green (sum of high and low) within several radii (100-3000 m) around the residence after geocoding of the addresses., Main Outcomes and Measures: Radial bone mineral density was assessed using quantitative ultrasound measurement at follow-up, measured as the mean of the axially transmitted speed of sound in meters per second. Multiple linear and logistic regression models were used while accounting for relevant covariates and potential confounders., Results: The study population comprised 327 children (180 [55.0%] female; mean [SD] age, 4.6 [0.4] years at the follow-up evaluation). Early-life exposure to residential green space was associated with increased childhood bone health. An IQR increment in total green (21.2%) and high green (19.9%) space within 500 m was associated with an increase of 27.38 m/s (95% CI, 9.63-45.13 m/s) and 25.30 m/s (95% CI, 7.93-42.68 m/s) in bone mineral density, respectively. Additionally, an IQR increase in total (25.2%) and high (23.2%) green space within 1000 m was associated with a 67% (odds ratio, 0.33; 95% CI, 0.17-0.61) and 61% (odds ratio, 0.39; 95% CI, 0.18-0.75) lower risk of having a bone density lower than the sex-specific 10th percentile (3567.6 m/s for girls and 3522.8 m/s for boys)., Conclusions and Relevance: In this study of children aged 4 to 6 years, higher bone mineral density and a lower risk of having low bone density were associated with higher residential green space exposure during childhood. These findings highlight the importance of early-life exposure to residential green space on bone health during critical periods of growth and development, with long-term implications.
Published: 2024
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44. Data management and protection in occupational and environmental exposome research - A case study from the EU-funded EXIMIOUS project.

Author: Ghosh M, Broothaerts K, Ronsmans S, Roig IB, Scheepers J, Dikmen M, Ciscato ER, Blanch C, Plusquin M, Nygaard UC, Sejbæk CS, Hougaard KS, and Hoet PH
Abstract: Within collaborative projects, such as the EU-funded Horizon 2020 EXIMIOUS project (Mapping Exposure-Induced Immune Effects: Connecting the Exposome and the Immunome), collection and analysis of large volumes of data pose challenges in the domain of data management, with regards to both ethical and legal aspects. However, researchers often lack the right tools and/or accurate understanding of the ethical/legal framework to independently address such challenges. With the guidance and support within and between the partner institutes (the researchers and the ethical and legal teams) in the EXIMIOUS project, we have been able to understand and solve most challenges during the first two project years. This has fed into the development of a Data Management Plan and the establishment of data management platforms in accordance with the ethical and legal framework laid down by the EU and the different national regulations of the partners involved. Through this elaborate exercise, we have acquired tools which allow us to make our research data FAIR (Findable, Accessible, Interoperable, and Reusable), while at the same time ensuring data privacy and security (GDPR compliant). Herein we share our experience of creating and managing the data workflow through an open research communication, with the aim of helping other researchers build their data management framework in their own projects. Based on the measures adopted in EXIMIOUS to ensure FAIR data management, we also put together a checklist "DMP CHECK" containing a series of recommendations based on our experience., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Manosij Ghosh, Peter Hoet reports financial support was provided by H2020 874707., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2023
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45. Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude.

Author: Kadalayil L, Alam MZ, White CH, Ghantous A, Walton E, Gruzieva O, Merid SK, Kumar A, Roy RP, Solomon O, Huen K, Eskenazi B, Rzehak P, Grote V, Langhendries JP, Verduci E, Ferre N, Gruszfeld D, Gao L, Guan W, Zeng X, Schisterman EF, Dou JF, Bakulski KM, Feinberg JI, Soomro MH, Pesce G, Baiz N, Isaevska E, Plusquin M, Vafeiadi M, Roumeliotaki T, Langie SAS, Standaert A, Allard C, Perron P, Bouchard L, van Meel ER, Felix JF, Jaddoe VWV, Yousefi PD, Ramlau-Hansen CH, Relton CL, Tobi EW, Starling AP, Yang IV, Llambrich M, Santorelli G, Lepeule J, Salas LA, Bustamante M, Ewart SL, Zhang H, Karmaus W, Röder S, Zenclussen AC, Jin J, Nystad W, Page CM, Magnus M, Jima DD, Hoyo C, Maguire RL, Kvist T, Czamara D, Räikkönen K, Gong T, Ullemar V, Rifas-Shiman SL, Oken E, Almqvist C, Karlsson R, Lahti J, Murphy SK, Håberg SE, London S, Herberth G, Arshad H, Sunyer J, Grazuleviciene R, Dabelea D, Steegers-Theunissen RPM, Nohr EA, Sørensen TIA, Duijts L, Hivert MF, Nelen V, Popovic M, Kogevinas M, Nawrot TS, Herceg Z, Annesi-Maesano I, Fallin MD, Yeung E, Breton CV, Koletzko B, Holland N, Wiemels JL, Melén E, Sharp GC, Silver MJ, Rezwan FI, and Holloway JW
Subjects: Child, Child, Preschool, Humans, Infant, Infant, Newborn, Carcinogenesis, Inflammation, Seasons, Asthma, DNA Methylation
Abstract: Background: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear., Methods: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points., Results: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N)., Conclusions: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)
Published: 2023
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46. The association between newborn cord blood steroids and ambient prenatal exposure to air pollution: findings from the ENVIRONAGE birth cohort.

Author: Plusquin M, Wang C, Cosemans C, Roels HA, Vangeneugden M, Lapauw B, Fiers T, T'Sjoen G, and Nawrot TS
Subjects: Infant, Newborn, Female, Pregnancy, Humans, 17-alpha-Hydroxypregnenolone, Androstenedione, Bayes Theorem, Birth Cohort, Fetal Blood, Nitrogen Dioxide, Steroids, Particulate Matter adverse effects, Prenatal Exposure Delayed Effects epidemiology, Air Pollution adverse effects, Air Pollutants adverse effects
Abstract: Knowledge of whether prenatal exposure to ambient air pollution disrupts steroidogenesis is currently lacking. We investigated the association between prenatal ambient air pollution and highly accurate measurements of cord blood steroid hormones from the androgenic pathway.This study included 397 newborns born between the years 2010 and 2015 from the ENVIRONAGE cohort in Belgium of whom six cord blood steroid levels were measured: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone, androstenedione, and testosterone. Maternal ambient exposure to PM 2.5 (particles with aerodynamic diameter ≤ 2.5 μm), NO 2, and black carbon (BC) were estimated daily during the entire pregnancy using a high-resolution spatiotemporal model. The associations between the cord blood steroids and the air pollutants were tested and estimated by first fitting linear regression models and followed by fitting weekly prenatal exposures to distributed lag models (DLM). These analyses accounted for possible confounders, coexposures, and an interaction effect between sex and the exposure. We examined mixture effects and critical exposure windows of PM 2.5 , NO 2 and BC on cord blood steroids via the Bayesian kernel machine regression distributed lag model (BKMR-DLM).An interquartile range (IQR) increment of 7.96 µg/m 3 in PM 2.5 exposure during pregnancy trimester 3 was associated with an increase of 23.01% (99% confidence interval: 3.26-46.54%) in cord blood levels of 17α-hydroxypregnenolone, and an IQR increment of 0.58 µg/m³ in BC exposure during trimester 1 was associated with a decrease of 11.00% (99% CI: -19.86 to -0.012%) in cord blood levels of androstenedione. For these two models, the DLM statistics identified sensitive gestational time windows for cord blood steroids and ambient air pollution exposures, in particular for 17α-hydroxypregnenolone and PM 2.5 exposure during trimester 3 (weeks 28-36) and for androsterone and BC exposure during early pregnancy (weeks 2-13) as well as during mid-pregnancy (weeks 18-26). We identified interaction effects between pollutants, which has been suggested especially for NO 2 .Our results suggest that prenatal exposure to ambient air pollutants during pregnancy interferes with steroid levels in cord blood. Further studies should investigate potential early-life action mechanisms and possible later-in-life adverse effects of hormonal disturbances due to air pollution exposure., (© 2023. BioMed Central Ltd., part of Springer Nature.)
Published: 2023
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47. Exposure to endocrine disrupters and cardiometabolic health effects in preschool children: Urinary parabens are associated with wider retinal venular vessels.

Author: Reimann B, Sleurs H, Dockx Y, Rasking L, De Boever P, Pirard C, Charlier C, Nawrot TS, and Plusquin M
Subjects: Child, Child, Preschool, Female, Humans, Male, Cross-Sectional Studies, Cardiovascular Diseases urine, Environmental Exposure statistics & numerical data, Environmental Pollutants analysis, Parabens metabolism
Abstract: Background and Aim: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life., Methods: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms., Results: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) μg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (β = 1.23, p = 0.039) and PrP with the retinal tortuosity index (x10 3) (β = 1.75, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (β = -0.067, p = 0.015 and β = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (β = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (β = 0.10, p = 0.060)., Conclusions: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Published: 2023
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48. Ambient black carbon reaches the kidneys.

Author: Rasking L, Koshy P, Bongaerts E, Bové H, Ameloot M, Plusquin M, De Vusser K, and Nawrot TS
Subjects: Humans, Biomarkers, Carbon adverse effects, Carbon analysis, Kidney chemistry, Particulate Matter adverse effects, Particulate Matter analysis, Air Pollutants adverse effects, Air Pollutants analysis, Air Pollution analysis, Soot adverse effects, Soot analysis
Abstract: Background: Ultrafine particles, including black carbon (BC), can reach the systemic circulation and therefore may distribute to distant organs upon inhalation. The kidneys may be particularly vulnerable to the adverse effects of BC exposure due to their filtration function., Objectives: We hypothesized that BC particles reach the kidneys via the systemic circulation, where the particles may reside in structural components of kidney tissue and impair kidney function., Methods: In kidney biopsies from 25 transplant patients, we visualized BC particles using white light generation under femtosecond-pulsed illumination. The presence of urinary kidney injury molecule-1 (KIM-1) and cystatin c (CysC) were evaluated with ELISA. We assessed the association between internal and external exposure matrices and urinary biomarkers using Pearson correlation and linear regression models., Results: BC particles could be identified in all biopsy samples with a geometric mean (5th, 95th percentile) of 1.80 × 10 3 (3.65 × 10 2 , 7.50 × 10 3 ) particles/mm 3 kidney tissue, predominantly observed in the interstitium (100 %) and tubules (80 %), followed by the blood vessels and capillaries (40 %), and the glomerulus (24 %). Independent from covariates and potential confounders, we found that each 10 % higher tissue BC load resulted in 8.24 % (p = 0.03) higher urinary KIM-1. In addition, residential proximity to a major road was inversely associated with urinary CysC (+10 % distance: -4.68 %; p = 0.01) and KIM-1 (+10 % distance: -3.99 %; p < 0.01). Other urinary biomarkers, e.g., the estimated glomerular filtration rate or creatinine clearance showed no significant associations., Discussion and Conclusion: Our findings that BC particles accumulate near different structural components of the kidney represent a potential mechanism explaining the detrimental effects of particle air pollution exposure on kidney function. Furthermore, urinary KIM-1 and CysC show potential as air pollution-induced kidney injury biomarkers for taking a first step in addressing the adverse effects BC might exert on kidney function., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H.B., M.A., and T.S.N. declare that aspects of the work are subject of a patent application (Method for detecting or quantifying carbon black and/or black carbon particles, US20190025215A1) filed by Hasselt University (Hasselt, Belgium) and KU Leuven (Leuven, Belgium). The remaining authors declare no competing interests. None of the funding agencies had a role in the design and conduct of the study, in the collection, analysis and interpretation of the data, or in the preparation, review, or approval of the manuscript., (Copyright © 2023. Published by Elsevier Ltd.)
Published: 2023
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49. Residential green space improves cognitive performances in primary schoolchildren independent of traffic-related air pollution exposure.

Author: Saenen ND, Nawrot TS, Hautekiet P, Wang C, Roels HA, Dadvand P, Plusquin M, and Bijnens EM
Subjects: Child, Humans, Parks, Recreational, Environmental Exposure adverse effects, Environmental Exposure analysis, Nitrogen Dioxide analysis, Cognition, Particulate Matter analysis, Air Pollutants adverse effects, Air Pollutants analysis, Air Pollution analysis
Abstract: Background: Cognitive performances of schoolchildren have been adversely associated with both recent and chronic exposure to ambient air pollution at the residence. In addition, growing evidence indicates that exposure to green space is associated with a wide range of health benefits. Therefore, we aimed to investigate if surrounding green space at the residence improves cognitive performance of primary schoolchildren while taking into account air pollution exposure., Methods: Cognitive performance tests were administered repeatedly to a total of 307 primary schoolchildren aged 9-12y, living in Flanders, Belgium (2012-2014). These tests covered three cognitive domains: attention (Stroop and Continuous Performance Tests), short-term memory (Digit Span Forward and Backward Tests), and visual information processing speed (Digit-Symbol and Pattern Comparison Tests). Green space exposure was estimated within several radii around their current residence (50 m to 2000 m), using a aerial photo-derived high-resolution (1 m 2 ) land cover map. Furthermore, air pollution exposure to PM 2.5 and NO 2 during the year before examination was modelled for the child's residence using a spatial-temporal interpolation method., Results: An improvement of the children's attention was found with more residential green space exposure independent of traffic-related air pollution. For an interquartile range increment (21%) of green space within 100 m of the residence, a significantly lower mean reaction time was observed independent of NO 2 for both the sustained-selective (-9.74 ms, 95% CI: -16.6 to -2.9 ms, p = 0.006) and the selective attention outcomes (-65.90 ms, 95% CI: -117.0 to -14.8 ms, p = 0.01). Moreover, green space exposure within a large radius (2000 m) around the residence was significantly associated with a better performance in short-term memory (Digit-Span Forward Test) and a higher visual information processing speed (Pattern Comparison Test), taking into account traffic-related exposure. However, all associations were attenuated after taking into account long-term residential PM 2.5 exposure., Conclusions: Our panel study showed that exposure to residential surrounding green space was associated with better cognitive performances at 9-12 years of age, taking into account traffic-related air pollution exposure. These findings support the necessity to build attractive green spaces in the residential environment to promote healthy cognitive development in children., (© 2023. The Author(s).)
Published: 2023
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50. Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth.

Author: Alfano R, Zugna D, Barros H, Bustamante M, Chatzi L, Ghantous A, Herceg Z, Keski-Rahkonen P, de Kok TM, Nawrot TS, Relton CL, Robinson O, Roumeliotaki T, Scalbert A, Vrijheid M, Vineis P, Richiardi L, and Plusquin M
Subjects: Pregnancy, Female, Humans, Child, Fetal Blood, DNA Methylation genetics, Birth Weight genetics, CpG Islands, Genome-Wide Association Study, Kruppel-Like Transcription Factors genetics, Epigenome genetics, Pediatric Obesity genetics
Abstract: Background: Rapid postnatal growth may result from exposure in utero or early life to adverse conditions and has been associated with diseases later in life and, in particular, with childhood obesity. DNA methylation, interfacing early-life exposures and subsequent diseases, is a possible mechanism underlying early-life programming., Methods: Here, a meta-analysis of Illumina HumanMethylation 450K/EPIC-array associations of cord blood DNA methylation at single CpG sites and CpG genomic regions with rapid weight growth at 1 year of age (defined with reference to WHO growth charts) was conducted in six European-based child cohorts (ALSPAC, ENVIRONAGE, Generation XXI, INMA, Piccolipiù, and RHEA, N = 2003). The association of gestational age acceleration (calculated using the Bohlin epigenetic clock) with rapid weight growth was also explored via meta-analysis. Follow-up analyses of identified DNA methylation signals included prediction of rapid weight growth, mediation of the effect of conventional risk factors on rapid weight growth, integration with transcriptomics and metabolomics, association with overweight in childhood (between 4 and 8 years), and comparison with previous findings., Results: Forty-seven CpGs were associated with rapid weight growth at suggestive p-value <1e-05 and, among them, three CpGs (cg14459032, cg25953130 annotated to ARID5B, and cg00049440 annotated to KLF9) passed the genome-wide significance level (p-value <1.25e-07). Sixteen differentially methylated regions (DMRs) were identified as associated with rapid weight growth at false discovery rate (FDR)-adjusted/Siddak p-values < 0.01. Gestational age acceleration was associated with decreasing risk of rapid weight growth (p-value = 9.75e-04). Identified DNA methylation signals slightly increased the prediction of rapid weight growth in addition to conventional risk factors. Among the identified signals, three CpGs partially mediated the effect of gestational age on rapid weight growth. Both CpGs (N=3) and DMRs (N=3) were associated with differential expression of transcripts (N=10 and 7, respectively), including long non-coding RNAs. An AURKC DMR was associated with childhood overweight. We observed enrichment of CpGs previously reported associated with birthweight., Conclusions: Our findings provide evidence of the association between cord blood DNA methylation and rapid weight growth and suggest links with prenatal exposures and association with childhood obesity providing opportunities for early prevention., (© 2023. The Author(s).)
Published: 2023
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