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1. 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

2. 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

3. Longitudinal associations of DNA methylation and sleep in children: a meta‑analysis

Author

Sammallahti, S., Koopman‑Verhoeff, M.E., Binter, A.-C., Mulder, R.H., Cabré‑Riera, A., Kvist, T., Malmberg, A.L.K., Pesce, G., Plancoulaine, S., Heiss, J.A., Rifas‐Shiman, S.L., Röder, Stefan, Starling, A.P., Wilson, R., Guerlich, K., Haftorn, K.L., Page, C.M., Luik, A.I., Tiemeier, H., Felix, J.F., Raikkonen, K., Lahti, J., Relton, C.L., Sharp, G.C., Waldenberger, M., Grote, V., Heude, B., Annesi‑Maesano, I., Hivert, M.-F., Zenclussen, Ana Claudia, Herberth, Gunda, Dabelea, D., Grazuleviciene, R., Vafeiadi, M., Håberg, S.E., London, S.J., Guxens, M., Richmond, R.C., Cecil, C.A.M., Sammallahti, S., Koopman‑Verhoeff, M.E., Binter, A.-C., Mulder, R.H., Cabré‑Riera, A., Kvist, T., Malmberg, A.L.K., Pesce, G., Plancoulaine, S., Heiss, J.A., Rifas‐Shiman, S.L., Röder, Stefan, Starling, A.P., Wilson, R., Guerlich, K., Haftorn, K.L., Page, C.M., Luik, A.I., Tiemeier, H., Felix, J.F., Raikkonen, K., Lahti, J., Relton, C.L., Sharp, G.C., Waldenberger, M., Grote, V., Heude, B., Annesi‑Maesano, I., Hivert, M.-F., Zenclussen, Ana Claudia, Herberth, Gunda, Dabelea, D., Grazuleviciene, R., Vafeiadi, M., Håberg, S.E., London, S.J., Guxens, M., Richmond, R.C., and Cecil, C.A.M.

Abstract

Background Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available. &nbsp

Published
2022

4. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

Author

Vehmeijer, F.O.L. (Florianne O.L.), Küpers, A.M. (Marlijn), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Lent, S. (Samantha), Jima, D.D. (Dereje D.), Tindula, G. (Gwen), Reese, S.E. (Sarah E.), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F.I. (Faisal I.), Melton, P.E. (Philip E.), Nohr, C. (Christian), Escaramís, G. (Geòrgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S.T. (Samuli T.), Gao, L. (Lu), Ross, J.P. (Jason P.), Starling, A.P. (Anne P.), Holloway, J.W. (John W.), Yousefi, P. (Paul), Aasvang, G.M. (Gunn Marit), Beilin, L.J. (Lawrence), Bergström, A. (Anna), Binder, E.B. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (B.), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Håberg, S.E. (Siri E), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, C.A. (Christian), Langhendries, J.P. (Jean Paul), Lepeule, J. (Johanna), Magnus, M.C. (Maria C.), Maguire, R.L. (Rachel L.), Molloy, P.L. (Peter L.), Poppelaars-Monnereau, C. (Claire), Mori, T.A. (Trevor A.), Oken, E. (Emily), Räikkönen, K. (Katri), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J.M. (Judith), Xu, C.-J. (Cheng-Jian), Yang, I.V. (Ivana V.), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B.S. (Beverly S.), Breton, C. (Carrie), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sørensen, T.I.A. (Thorkild), Huang, R.-C. (Rae-Chi), Arshad, S.H. (Syed), Nystad, W. (Wenche), Melén, E. (Erik), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S.K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A.A. (Andrea), Relton, C.L. (Caroline), Snieder, H. (Harold), Jaddoe, V.W.V. (Vincent), Felix, J.F. (Janine), Vehmeijer, F.O.L. (Florianne O.L.), Küpers, A.M. (Marlijn), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Lent, S. (Samantha), Jima, D.D. (Dereje D.), Tindula, G. (Gwen), Reese, S.E. (Sarah E.), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F.I. (Faisal I.), Melton, P.E. (Philip E.), Nohr, C. (Christian), Escaramís, G. (Geòrgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S.T. (Samuli T.), Gao, L. (Lu), Ross, J.P. (Jason P.), Starling, A.P. (Anne P.), Holloway, J.W. (John W.), Yousefi, P. (Paul), Aasvang, G.M. (Gunn Marit), Beilin, L.J. (Lawrence), Bergström, A. (Anna), Binder, E.B. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (B.), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Håberg, S.E. (Siri E), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, C.A. (Christian), Langhendries, J.P. (Jean Paul), Lepeule, J. (Johanna), Magnus, M.C. (Maria C.), Maguire, R.L. (Rachel L.), Molloy, P.L. (Peter L.), Poppelaars-Monnereau, C. (Claire), Mori, T.A. (Trevor A.), Oken, E. (Emily), Räikkönen, K. (Katri), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J.M. (Judith), Xu, C.-J. (Cheng-Jian), Yang, I.V. (Ivana V.), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B.S. (Beverly S.), Breton, C. (Carrie), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sørensen, T.I.A. (Thorkild), Huang, R.-C. (Rae-Chi), Arshad, S.H. (Syed), Nystad, W. (Wenche), Melén, E. (Erik), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S.K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A.A. (Andrea), Relton, C.L. (Caroline), Snieder, H. (Harold), Jaddoe, V.W.V. (Vincent), and Felix, J.F. (Janine)

Abstract

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10−7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7). Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI.

Published
2020
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9. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns Findings From the Pregnancy and Childhood Epigenetics Consortium

Author

Kazmi, N., Sharp, G.C. (Gregory), Reese, SE, Vehmeijer, F.O., Lahti, J. (Jari), Page, CM, Zhang, W.M., Rifas-Shiman, S.L. (Sheryl L.), Rezwan, F.I., Simpkin, A.J., Burrows, K., Richardson, T.G., Ferreira, D. L. S., Fraser, A, Harmon, Q.E., Zhao, S.S., Jaddoe, V.W.V. (Vincent), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Magnus, M.C., Håberg, S.E. (Siri E), Nystad, W. (Wenche), Nohr, C. (Christian), Starling, A.P., Kechris, K.J., Yang, I.V., Demeo, D.L. (Dawn), Litonjua, AA, Baccarelli, A., Oken, E. (Emily), Holloway, J.W. (John), Karmaus, W, Arshad, S.H. (Syed), Dabelea, D., Sorensen, H.G., Laivuori, H, Raikkonen, K. (Katri), Felix, J.F. (Janine), London, S.J. (Stephanie), Hivert, M.-F. (Marie-France), Gaunt, T.R. (Tom), Lawlor, D.A. (Debbie), Relton, C.L. (Caroline), Kazmi, N., Sharp, G.C. (Gregory), Reese, SE, Vehmeijer, F.O., Lahti, J. (Jari), Page, CM, Zhang, W.M., Rifas-Shiman, S.L. (Sheryl L.), Rezwan, F.I., Simpkin, A.J., Burrows, K., Richardson, T.G., Ferreira, D. L. S., Fraser, A, Harmon, Q.E., Zhao, S.S., Jaddoe, V.W.V. (Vincent), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Magnus, M.C., Håberg, S.E. (Siri E), Nystad, W. (Wenche), Nohr, C. (Christian), Starling, A.P., Kechris, K.J., Yang, I.V., Demeo, D.L. (Dawn), Litonjua, AA, Baccarelli, A., Oken, E. (Emily), Holloway, J.W. (John), Karmaus, W, Arshad, S.H. (Syed), Dabelea, D., Sorensen, H.G., Laivuori, H, Raikkonen, K. (Katri), Felix, J.F. (Janine), London, S.J. (Stephanie), Hivert, M.-F. (Marie-France), Gaunt, T.R. (Tom), Lawlor, D.A. (Debbie), and Relton, C.L. (Caroline)

Abstract

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

Published
2019
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10. Effects of gel phase phospholipid on the Ca2+-ATPase

Author

Starling, A.P., East, J.M., and Lee, A.G.

Subjects
Adenosine triphosphatase -- Research, Phospholipids -- Physiological aspects, Biological sciences, Chemistry
Abstract

Examination of the activity of ATPase toward Ca2+, in dipalmitoylphosphatidylcholine in both the gel phase and the crystalline phase, reveals that ATPase exhibits higher affinity for Ca2+ in the gel phase than in the liquid-crystalline phase. The phase of the lipid exerts no influence on the conformational change arising from the binding of ATP to the ATPase, while it influences the kinetics of phosphate transfer.

Published
1995

11. Binding sites for cholesterol on Ca(sup 2+)-ATPase studied by using a cholesterol-containing phospholipid

Author

Ding, J., Starling, A.P., East, J.M., and Lee, A.G.

Subjects
Binding sites (Biochemistry) -- Analysis, Cholesterol -- Analysis, Adenosine triphosphatase -- Analysis, Biological sciences, Chemistry
Abstract

Cholesterol-containing phosphatidylcholines can interact with Ca2+-ATPase only at the lipid-protein interface. This is revealed by fluorescence quenching studies. This interaction is from skeletal muscle sarcoplasmic reticulum. Affinity for interaction is half in comparison with that of dioleoylphosphatidylcholine.

Published
1994

12. Mechanism of inhibition of the Ca(sup 2+)-ATPase by spermine and other polycationic compounds

Author

Hughes, G., Starling, A.P., East, J.M., and Lee, A.G.

Subjects
Phosphorylation -- Analysis, Adenosine triphosphatase -- Research, Biological sciences, Chemistry
Abstract

The phosphorylation of ATPase with P(i) in the presence of dimethylsulfoxide as a catalyst stimulates dephosphorylation by dilution in the buffer. The dilution occurs in the dimethylsulfoxide. Dephosphorylation reaction is independent of the presence of spermine.

Published
1994

13. Mechanism of stimulation of the calcium adenosinetriphosphatase by jasmone

Author

Starling, A.P., Hughes, G., East, J.M., and Lee, A.G.

Subjects
Adenosine triphosphatase -- Analysis, Calcium ions -- Research, Sarcoplasmic reticulum -- Analysis, Biological sciences, Chemistry
Abstract

Stimulation at the ATPase activity is reduced when the ATPase activity of calcium ions ATPase of skeletal muscle sarcoplasmic reticulum is increased by a factor of 3. High concentration of muscle sarcoplasmic reticulum is required for stimulation by methyl jasmonate, menthone or menthol. The phosphorylation rate of ATPase is not influenced by jasmone, although jasmone acts as a catalyst in increasing phosphorylation rate.

Published
1994

14. Effects of phosphatidylcholine fatty acyl chain length on calcium binding and other functions of the (Ca2+-Mg2+)-ATPase

Author

Starling, A.P., East, J.M., and Lee, A.G.

Subjects
Lecithin -- Physiological aspects, Calcium ions -- Physiological aspects, Adenosine triphosphatase -- Research, Biological sciences, Chemistry
Abstract

The effects of phospholipids on the stoichiometry of Ca2+ binding to the ATPase were investigated and the effects of mixtures of phospholipids were studied. The stoichiometry of Ca2+ binding to the ATPase is sensitive to fatty acyl chain length. For the ATPase reconstituted with mixtures of phosphatidylcholine, a highly cooperative change in binding stoichiometry with change in phospholipid composition is observed, suggesting a conformation change dependent on phospholipid binding at a large number of sites at the lipid-protein interface.

Published
1993

15. 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
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19. Mechanism of inhibition of the Ca2+-ATPase by spermine and other polycationic compounds.

Author

Hughes, G. and Starling, A.P.

Subjects
*SPERMINE, *ADENOSINE triphosphatase, *CALCIUM, *CHEMICAL inhibitors, *PHYSIOLOGY
Abstract

Describes the inhibitory effects of spermine on the function of the Ca2+-ATPase of the skeletal muscle. Inhibition of steady-state activity by polycationic species; Effects on affinity of ATPase for Ca2+; Effect on equilibrium of ATPase; Effect on phosphorylation and dephosphorylation of ATPase; Effect on rate of dissociation of Ca2+; Effects on lipid bilayers.

Published
1994
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20. The Hydrophilic Domain of Phospholamban Inhibits the Ca2+-ATPase - The Importance of the Method of Assay

Author

Starling, A.P., Hughes, G., Sharma, R.P., East, J.M., and Lee, A.G.

Abstract

The peptide MEKVQYLTRSAIRRASTIEMPQQAR-Cys representing residues 1-25 of phospholamban (PLN) decreases by 40 % the maximal state rate of ATP hydrolysis by the Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum (SR), measured at saturating concentrations of Ca2+. The pattern of Ca2+ uptake by SR vesicles in the presence of oxalate is complex, with an initial fast phase being followed by a lag phase and a second, slower phase of Ca2+ accumulation. PLN(1-25) reduces the rate of the slower phase of Ca2+ accumulation by 30 %. However, if the level of accumulation of Ca2+ is measured after 2 min., the effect of PLN(1-25) is much less marked. It is concluded that PLN(1-25) inhibits the ATPase, but that the effects of this inhibition are not apparent under some assay conditions.Copyright 1995, 1999 Academic Press, Inc.

Published
1995
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