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52. 3rd IANA (International Academy on Nutrition and Aging) Meeting Nutrition, Exercise & Alzheimer and Clinical Trials on Sarcopenia August 1–2, 2008 Hyatt Regency Tamaya Resort 1300 Tuyuna Trail Santa Ana Pueblo, NM USA

Author

Andrieu, S., Barberger-Gateau, P., Raffaitin, C., Berr, C., Tzourio, C., Dartigues, J. -F., Gin, H., Fitten, L. J., Ortiz, F., Fairbanks, L., Bartzokis, G., Lu, P., Ringman, J., Heyn, P. C., Locher, J. L., Salvà, A., Andrieu, S., Fernández, E., Vellas, B., van de Rest, O., Geleijnse, J. M., Kok, F. J., van Staveren, W. A., Beekman, A. T. F., Hoefnagels, W. H. L., de Groot, C. P. G. M., Angevaren, M., Aufdemkampe, G., Verhaar, H. J. J., Aleman, A., Vannees, L., Arkin, S., Florez, H., Gerstein, H., Sheridan, P., Bosch, J., Goldberg, R., Kaspar, K. M., Drawert, S. M., Marcus, R. L., Kidde, J., Dibble, L., Addison, O., LaStayo, P. C., Scarmeas, N., Stern, Y., Schupf, N., Luchsinger, J. A., Sharkey, J. R., Laditka, J. N., Laditka, S. B., Liu, R., Hochhalter, A., Robare, J. F., Türner, N., Judge, M., Foster, T. C., Erdos, B., Cudykier, I., Scarpace, P. J., Weiss, L. A., Bergstrom, J., Kritz-Silverstein, D., Barrett-Connor, Elizabeth, Yurko-Mauro, K., Nelson, E., Quinn, J., Sattler, F. R., Castaneda-Sceppa, C., Binder, E. F., Schroeder, E. T., Wang, Y., Bhasin, S., Kawakubo, M., Stewart, Y., Hahn, C., Colletti, P., Roubenoff, R., Yarasheski, K. E., Azen, S. P., Aoki, Y., Yamamoto, T., Otuka, T., Blanc-Bisson, C., Bourdel-Marchasson, I., Bocock, M. A., Keller, H. H., Bowman, G., Baxter, J., Oken, B., Frei, B., Traber, M., Leonard, S., Kaye, J., Shannon, J., Quinn, J., Carlsson, M., Gustafson, Y., Eriksson, S., Littbrand, H., Håglin, L., Danthiir, V., Wilson, C., Nettelbeck, T., Burns, N., Wittert, G., Noakes, M., Clifton, P., DiMaria-Ghalili, R. A., Grieger, J. A., Nowson, C. A., Wattanapenpaiboon, N. T., Holstein, J., Robinson, C., Hartmann, C., Rueb, S., Heffel, L., Dintaman, S., Reynolds, J., Fleming, L., Crull, M., Goldey, J., Serper, L. L., Hubbard, R., Westengard, J., Horning, M., Ishige, Y., Aoki, Y., Keller, H. H., Keller, H. H., LaStayo, P. C., Marcus, R. L., Smith, S., Kidde, J., Dibble, L., Butler, C., Hill, M., LaStayo, P. C., Marcus, R. L., Dibble, L., Kidde, J., Peters, C., Meier, W., Laughlin, G. A., Kritz-Silverstein, D., von Muhlen, D., Barrett-Connor, E., Olariu, L., Petcu, M., Tulcan, C., Pup, M., Otilingam, P., Gate, M., Pasinetti, G. M., Ray, B., Chauhan, N. B., Bailey, J. A., Lahiri, D. K., Shatenstein, B., Kergoat, M. -J., Reid, I., Chicoine, M. -E., Vaz, L., Stewart, R., Sabbah, W., Tsakos, G., D’Aiuto, F., Watt, R. G., Sturman, M., Kelly, J., Fleischman, D., Leurgans, S., Bennett, D., Morris, M. C., Suominen, M. H., Muurinen, S., Soini, H., Pitkälä, K. H., Yamamoto, T., Fujinoki, C., and Aoki, Y.

Published
2008
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55. A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders

Author

Suarez, A. (Anna), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Czamara, D. (Darina), Arloth, J. (Janine), Malmberg, A. L. (Anni LK.), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Reynolds, R. M. (Rebecca M.), Provençal, N. (Nadine), Binder, E. B. (Elisabeth B.), and Räikkönen, K. (Katri)

Subjects
Cord blood methylation, Childhood mental health, Polyepigenetic biomarker, Prospective study, Glucocorticoids, Prenatal psychopathology
Abstract

Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes. Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child’s age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583). Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met. Conclusions: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders.

Published
2020

58. Polygenic prediction of the risk of perinatal depressive symptoms

Author

Rantalainen, V. (Ville), Binder, E. B. (Elisabeth B.), Lahti‐Pulkkinen, M. (Marius), Czamara, D. (Darina), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Girchenko, P. (Polina), Kvist, T. (Tuomas), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Lahti, J. (Jari), Räikkönen, K. (Katri), Rantalainen, V. (Ville), Binder, E. B. (Elisabeth B.), Lahti‐Pulkkinen, M. (Marius), Czamara, D. (Darina), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Girchenko, P. (Polina), Kvist, T. (Tuomas), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Lahti, J. (Jari), and Räikkönen, K. (Katri)

Abstract

Background: Perinatal depression carries adverse effects on maternal health and child development, but genetic underpinnings remain unclear. We investigated the polygenic risk of perinatal depressive symptoms. Methods: About 742 women from the prospective Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction cohort were genotyped and completed the Center for Epidemiologic Studies Depression scale 14 times during the prenatal period and twice up to 12 months postpartum. Polygenic risk scores for major depressive disorder, bipolar disorder, schizophrenia, and cross-disorder were calculated using multiple p-value thresholds. Results: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder, but not bipolar disorder, were associated with higher prenatal and postpartum depressive symptoms (0.8%–1% increase per one standard deviation increase in polygenic risk scores). Prenatal depressive symptoms accounted for and mediated the associations between the polygenic risk scores and postpartum depressive symptoms (effect size proportions-mediated: 52.2%–88.0%). Further, the polygenic risk scores were associated with 1.24–1.45-fold odds to belong to the group displaying consistently high compared with consistently low depressive symptoms through out the prenatal and postpartum periods. Conclusions: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder in non-perinatal populations generalize to perinatal depressive symptoms and may afford to identify women for timely preventive interventions.

Published
2020

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

Author

Vehmeijer, F. O. (Florianne O. L.), Kuepers, L. K. (Leanne K.), Sharp, G. C. (Gemma C.), Salas, L. A. (Lucas A.), Lent, S. (Samantha), Jima, D. D. (Dereje D.), Tindula, G. (Gwen), Reese, S. (Sarah), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F. I. (Faisal, I), Melton, P. E. (Philip E.), Nohr, E. (Ellen), Escaramis, G. (Georgia), 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 J.), Bergstrom, A. (Anna), Binder, E. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (Brenda), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Haberg, S. E. (Siri E.), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, I. (Inger), Langhendries, J.-P. (Jean-Paul), Lepeule, J. (Johanna), Magnus, M. C. (Maria C.), Maguire, R. L. (Rachel L.), Molloy, P. L. (Peter L.), Monnereau, C. (Claire), Mori, T. A. (Trevor A.), Oken, E. (Emily), Raikkonen, K. (Katri), Rifas-Shiman, S. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J. M. (Judith M.), 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. V. (Carrie, V), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sorensen, T. I. (Thorkild I. A.), Huang, R.-C. (Rae-Chi), Arshad, S. H. (Syed Hasan), Nystad, W. (Wenche), Melen, E. (Erik), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S. K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A. (Andrea), Relton, C. L. (Caroline L.), Snieder, H. (Harold), Jaddoe, V. W. (Vincent W. V.), Felix, J. F. (Janine F.), Vehmeijer, F. O. (Florianne O. L.), Kuepers, L. K. (Leanne K.), Sharp, G. C. (Gemma C.), Salas, L. A. (Lucas A.), Lent, S. (Samantha), Jima, D. D. (Dereje D.), Tindula, G. (Gwen), Reese, S. (Sarah), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F. I. (Faisal, I), Melton, P. E. (Philip E.), Nohr, E. (Ellen), Escaramis, G. (Georgia), 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 J.), Bergstrom, A. (Anna), Binder, E. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (Brenda), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Haberg, S. E. (Siri E.), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, I. (Inger), Langhendries, J.-P. (Jean-Paul), Lepeule, J. (Johanna), Magnus, M. C. (Maria C.), Maguire, R. L. (Rachel L.), Molloy, P. L. (Peter L.), Monnereau, C. (Claire), Mori, T. A. (Trevor A.), Oken, E. (Emily), Raikkonen, K. (Katri), Rifas-Shiman, S. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J. M. (Judith M.), 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. V. (Carrie, V), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sorensen, T. I. (Thorkild I. A.), Huang, R.-C. (Rae-Chi), Arshad, S. H. (Syed Hasan), Nystad, W. (Wenche), Melen, E. (Erik), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S. K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A. (Andrea), Relton, C. L. (Caroline L.), Snieder, H. (Harold), Jaddoe, V. W. (Vincent W. V.), and Felix, J. F. (Janine F.)

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 adol

Published
2020

60. 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

61. Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis

Author

Neumann, Alexander, Walton, E, Alemany, S, Cecil, Charlotte, González, JR, Jima, DD, Lahti, J, Tuominen, ST, Barker, ED, Binder, E, Caramaschi, D, Carracedo, Á, Czamara, D, Evandt, J, Felix, Janine, Fuemmeler, BF, Gutzkow, KB, Hoyo, C, Julvez, J, Kajantie, E, Laivuori, H, Maguire, R, Maitre, L, Murphy, SK, Murcia, M, Villa, PM, Sharp, G, Sunyer, J, Raikkönen, K, Bakermans-Kranenburg, M, van IJzendoorn, M, Guxens Junyent, Monica, Relton, CL, Tiemeier, Henning, Neumann, Alexander, Walton, E, Alemany, S, Cecil, Charlotte, González, JR, Jima, DD, Lahti, J, Tuominen, ST, Barker, ED, Binder, E, Caramaschi, D, Carracedo, Á, Czamara, D, Evandt, J, Felix, Janine, Fuemmeler, BF, Gutzkow, KB, Hoyo, C, Julvez, J, Kajantie, E, Laivuori, H, Maguire, R, Maitre, L, Murphy, SK, Murcia, M, Villa, PM, Sharp, G, Sunyer, J, Raikkönen, K, Bakermans-Kranenburg, M, van IJzendoorn, M, Guxens Junyent, Monica, Relton, CL, and Tiemeier, Henning

Published
2020

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

Author

Vehmeijer, Florianne, Küpers, LK, Sharp, GC, Salas, LA, Lent, S, Jima, DD, Tindula, G, Reese, S, Qi, C, Gruzieva, O, Page, C, Rezwan, FI, Melton, PE, Nohr, E, Escaramís, G, Rzehak, P, Heiskala, A, Gong, T, Tuominen, ST, Gao, L, Ross, JP, Starling, AP, Holloway, JW, Yousefi, P, Aasvang, GM, Beilin, LJ, Bergström, A, Binder, E, Chatzi, L, Corpeleijn, E, Czamara, D, Eskenazi, B, Ewart, S, Ferre, N, Grote, V, Gruszfeld, D, Håberg, SE, Hoyo, C, Huen, K, Karlsson, R, Kull, I, Langhendries, J P, Lepeule, J, Magnus, MC, Maguire, RL, Molloy, PL, Monnereau, Claire, Mori, TA, Oken, E, Räikkönen, K, Rifas-Shiman, S, Ruiz-Arenas, C, Sebert, S, Ullemar, V, Verduci, E, Vonk, JM, Xu, CJ, Yang, IV, Zhang, H, Zhang, W, Karmaus, W, Dabelea, D, Muhlhausler, BS, Breton, CV, Lahti, J, Almqvist, C, Jarvelin, M R R, Koletzko, B, Vrijheid, M, Sørensen, TIA, Huang, RC, Arshad, SH, Nystad, W, Melén, E, Koppelman, GH, London, SJ, Holland, N, Bustamante, M, Murphy, SK, Hivert, MF, Baccarelli, A, Relton, CL, Snieder, H, Jaddoe, Vincent, Felix, Janine, Vehmeijer, Florianne, Küpers, LK, Sharp, GC, Salas, LA, Lent, S, Jima, DD, Tindula, G, Reese, S, Qi, C, Gruzieva, O, Page, C, Rezwan, FI, Melton, PE, Nohr, E, Escaramís, G, Rzehak, P, Heiskala, A, Gong, T, Tuominen, ST, Gao, L, Ross, JP, Starling, AP, Holloway, JW, Yousefi, P, Aasvang, GM, Beilin, LJ, Bergström, A, Binder, E, Chatzi, L, Corpeleijn, E, Czamara, D, Eskenazi, B, Ewart, S, Ferre, N, Grote, V, Gruszfeld, D, Håberg, SE, Hoyo, C, Huen, K, Karlsson, R, Kull, I, Langhendries, J P, Lepeule, J, Magnus, MC, Maguire, RL, Molloy, PL, Monnereau, Claire, Mori, TA, Oken, E, Räikkönen, K, Rifas-Shiman, S, Ruiz-Arenas, C, Sebert, S, Ullemar, V, Verduci, E, Vonk, JM, Xu, CJ, Yang, IV, Zhang, H, Zhang, W, Karmaus, W, Dabelea, D, Muhlhausler, BS, Breton, CV, Lahti, J, Almqvist, C, Jarvelin, M R R, Koletzko, B, Vrijheid, M, Sørensen, TIA, Huang, RC, Arshad, SH, Nystad, W, Melén, E, Koppelman, GH, London, SJ, Holland, N, Bustamante, M, Murphy, SK, Hivert, MF, Baccarelli, A, Relton, CL, Snieder, H, Jaddoe, Vincent, and Felix, Janine

Published
2020

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

Author

Universitat Rovira i Virgili, Vehmeijer FOL; Küpers LK; Sharp GC; Salas LA; Lent S; Jima DD; Tindula G; Reese S; Qi C; Gruzieva O; Page C; Rezwan FI; Melton PE; Nohr E; Escaramís G; Rzehak P; Heiskala A; Gong T; Tuominen ST; Gao L; Ross JP; Starling AP; Holloway JW; Yousefi P; Aasvang GM; Beilin LJ; Bergström A; Binder E; Chatzi L; Corpeleijn E; Czamara D; Eskenazi B; Ewart S; Ferre N; Grote V; Gruszfeld D; Håberg SE; Hoyo C; Huen K; Karlsson R, Universitat Rovira i Virgili, and Vehmeijer FOL; Küpers LK; Sharp GC; Salas LA; Lent S; Jima DD; Tindula G; Reese S; Qi C; Gruzieva O; Page C; Rezwan FI; Melton PE; Nohr E; Escaramís G; Rzehak P; Heiskala A; Gong T; Tuominen ST; Gao L; Ross JP; Starling AP; Holloway JW; Yousefi P; Aasvang GM; Beilin LJ; Bergström A; Binder E; Chatzi L; Corpeleijn E; Czamara D; Eskenazi B; Ewart S; Ferre N; Grote V; Gruszfeld D; Håberg SE; Hoyo C; Huen K; Karlsson R

Abstract

© 2020, The Author(s). 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 ide

Published
2020

70. Estimating the heritability of reporting stressful life events captured by common genetic variants

Author

Power, R. A., Wingenbach, T., Cohen-Woods, S., Uher, R., Ng, M. Y., Butler, A. W., Ising, M., Craddock, N., Owen, M. J., Korszun, A., Jones, L., Jones, I., Gill, M., Rice, J. P., Maier, W., Zobel, A., Mors, O., Placentino, A., Rietschel, M., Lucae, S., Holsboer, F., Binder, E. B., Keers, R., Tozzi, F., Muglia, P., Breen, G., Craig, I. W., Müller-Myhsok, B., Kennedy, J. L., Strauss, J., Vincent, J. B., Lewis, C. M., Farmer, A. E., and McGuffin, P.

Published
2013

91. Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Author

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

Subjects
epigenetics, newborn, methylation, asthma, drug development, childhood
Abstract

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

Published
2019

94. Energy flow and charged particle spectra in deep inelastic scattering at HERA

Author

Abt, I., Ahmed, T., Andreev, V., Aid, S., Andrieu, B., Appuhn, R. -D., Arpagaus, M., Babaev, A., Bärwolff, H., Bán, J., Baranov, P., Barrelet, E., Bartel, W., Bassler, U., Beck, H. P., Behrend, H. -J., Belousov, A., Berger, Ch., Bergstein, H., Bernardi, G., Bernet, R., Bertrand-Coremans, G., Besançon, M., Biddulph, P., Binder, E., Bizot, J. C., Blobel, V., Borras, K., Bosetti, P. C., Boudry, V., Bourdarios, C., Braemer, A., Brasse, F., Braun, U., Braunschweig, W., Brisson, V., Bruncko, D., Büngener, L., Bürger, J., Büsser, F. W., Buniatian, A., Burke, S., Buschhorn, G., Campbell, A. J., Carli, T., Charles, F., Chyla, J., Clarke, D., Clegg, A. B., Colombo, M., Coughlan, J. A., Courau, A., Coutures, Ch., Cozzika, G., Criegee, L., Cvach, J., Dagoret, S., Dainton, J. B., Danilov, M., Dann, A. W. E., Dau, W. D., David, M., Deffur, E., Delcourt, B., Del Buono, L., Devel, M., De Roeck, A., Di Nezza, P., Dingus, P., Dollfus, C., Dowell, J. D., Dreis, H. B., Drescher, A., Duboc, J., Düllmann, D., Dünger, O., Duhm, H., Ebbinghaus, R., Eberle, M., Ebert, J., Ebert, T. R., Eckerlin, G., Efremenko, V., Egli, S., Ehrlichmann, H., Eichenberger, S., Eichler, R., Eisele, F., Eisenhandler, E., Ellis, N. N., Ellison, R. J., Elsen, E., Erdmann, M., Evrard, E., Favart, L., Fedotov, A., Feeken, D., Felst, R., Feltesse, J., Fensome, I. F., Ferencei, J., Ferrarotto, F., Flamm, K., Flauger, W., Fleischer, M., Flieser, M., Flügge, G., Fomenko, A., Fominykh, B., Forbush, M., Formánek, J., Foster, J. M., Franke, G., Fretwurst, E., Fuhrmann, P., Gabathuler, E., Gamerdinger, K., Garvey, J., Gayler, J., Gebauer, M., Gellrich, A., Gennis, M., Genzel, H., Gerhards, R., Godfrey, L., Goerlach, U., Goerlich, L., Gogitidze, N., Goldberg, M., Goldner, D., Goodall, A. M., Gorelov, I., Goritchev, P., Grab, C., Grässler, H., Grässler, R., Greenshaw, T., Greif, H., Grindhammer, G., Gruber, A., Gruber, C., Haack, J., Haidt, D., Hajduk, L., Hamon, O., Hampel, M., Hanlon, E. M., Hapke, M., Harjes, J., Haydar, R., Haynes, W. J., Heatherington, J., Hedberg, V., Heinzelmann, G., Henderson, R. C. W., Henschel, H., Herma, R., Herynek, I., Hildesheim, W., Hill, P., Hilton, C. D., Hladký, J., Hoeger, K. C., Höppner, M., Huet, Ph., Hufnagel, H., Huot, N., Ibbotson, M., Itterbeck, H., Jabiol, M. -A., Jacholkowska, A., Jacobsson, C., Jaffre, M., Jansen, T., Jönsson, L., Johannsen, K., Johnson, D. P., Johnson, L., Jung, H., Kalmus, P. I. P., Kant, D., Kazarian, S., Kaschowitz, R., Kasselmann, P., Kathage, U., Kaufmann, H. H., Kenyon, I. R., Kermiche, S., Keuker, C., Kiesling, C., Klein, M., Kleinwort, C., Knies, G., Ko, W., Köhler, T., Kolanoski, H., Kole, F., Kolya, S. D., Korbel, V., Korn, M., Kostka, P., Kotelnikov, S. K., Krasny, M. W., Krücker, D., Krüger, U., Kubenka, J. P., Küster, H., Kuhlen, M., Kurča, T., Kurzhöfer, J., Kuznik, B., Lacour, D., Lamarche, F., Lander, R., Landon, M. P. J., Lange, W., Langkau, R., Lanius, P., Laporte, J. F., Lebedev, A., Leuschner, A., Leverenz, C., Levonian, S., Lewin, D., Ley, Ch., Lindner, A., Lindström, G., Linsel, F., Lipinski, J., Loch, P., Lohmander, H., Lopez, G. C., Lüers, D., Lüke, D., Magnussen, N., Malinovski, E., Mani, S., Marage, P., Marks, J., Marshall, R., Martens, J., Martin, R., Martyn, H. -U., Martyniak, J., Masson, S., Mavroidis, A., Maxfield, S. J., McMahon, S. J., Mehta, A., Meier, K., Mercer, D., Merz, T., Meyer, C. A., Meyer, H., Meyer, J., Mikocki, S., Monnier, E., Moreau, F., Moreels, J., Morris, J. V., Müller, K., Murín, P., Murray, S. A., Nagovizin, V., Naroska, B., Naumann, Th., Newman, P. R., Newton, D., Neyret, D., Nguyen, H. K., Niebergall, F., Niebuhr, C., Nisius, R., Nowak, G., Noyes, G. W., Nyberg, M., Oberlack, H., Obrock, U., Olsson, J. E., Orenstein, S., Ould-Saada, F., Pascaud, C., Patel, G. D., Peppel, E., Peters, S., Phillips, H. T., Phillips, J. P., Pichler, Ch., Pilgram, W., Pitzl, D., Prell, S., Prosi, R., Rädel, G., Raupach, F., Rauschnabel, K., Reimer, P., Reinshagen, S., Ribarics, P., Riech, V., Riedlberger, J., Riess, S., Rietz, M., Robertson, S. M., Robmann, P., Roosen, R., Rosenbauer, K., Rostovtsev, A., Royon, C., Rudowicz, M., Ruffer, M., Rusakov, S., Rybicki, K., Sahlmann, N., Sanchez, E., Sankey, D. P. C., Savitsky, M., Schacht, P., Schleper, P., von Schlippe, W., Schmidt, C., Schmidt, D., Schmitz, W., Schöning, A., Schröder, V., Schuhmann, E., Schulz, M., Schwab, B., Schwind, A., Scobel, W., Seehausen, U., Sell, R., Semenov, A., Shekelyan, V., Sheviakov, I., Shooshtari, H., Shtarkov, L. N., Siegmon, G., Siewert, U., Sirois, Y., Skillicorn, I. O., Smirnov, P., Smith, J. R., Soloviev, Y., Spitzer, H., Steenbock, M., Steffen, P., Steinberg, R., Stella, B., Stephens, K., Stier, J., Stösslein, U., Strachota, J., Straumann, U., Struczinski, W., Sutton, J. P., Taylor, R. E., Tchernyshov, V., Thiebaux, C., Thompson, G., Tichomirov, I., Truöl, P., Turnau, J., Tutas, J., Urban, L., Usik, A., Valkar, S., Valkarova, A., Vallée, C., Van Esch, P., Vartapetian, A., Vazdik, Y., Vecko, M., Verrecchia, P., Vick, R., Villet, G., Vogel, E., Wacker, K., Walker, I. W., Walther, A., Weber, G., Wegener, D., Wegener, A., Wellisch, H. P., West, L. R., Willard, S., Winde, M., Winter, G. -G., Wolff, Th., Womersley, L. A., Wright, A. E., Wulff, N., Yiou, T. P., Žáček, J., Zeitnitz, C., Ziaeepour, H., Zimmer, M., Zimmermann, W., Zomer, F., and H1 Collaboration

Published
1994
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95. A measurement of multi-jet rates in deep-inelastic scattering at HERA

Author

Abt, I., Ahmed, T., Andreev, V., Andrieu, B., Appuhn, R. -D., Arpagaus, M., Babaev, A., Bärwolff, H., Bán, J., Baranov, P., Barrelet, E., Bartel, W., Bassler, U., Beck, H. P., Behrend, H. -J., Belousov, A., Berger, Ch., Bergstein, H., Bernardi, G., Bernet, R., Bertrand-Coremans, G., Besançon, M., Biddulph, P., Binder, E., Bischoff, A., Bizot, J. C., Blobel, V., Borras, K., Bosetti, P. C., Boudry, V., Bourdarios, C., Brasse, F., Braun, U., Braunschweig, W., Brisson, V., Bruncko, D., Büngener, L., Bürger, J., Büsser, F. W., Buniatian, A., Burke, S., Buschhorn, G., Campbell, A. J., Carli, T., Charles, F., Clarke, D., Clegg, A. B., Colombo, M., Coughlan, J. A., Courau, A., Coutures, Ch., Cozzika, G., Criegee, L., Cvach, J., Dagoret, S., Dainton, J. B., Danilov, M., Dann, A. W. E., Dau, W. D., David, M., Deffur, E., Delcourt, B., Del Buono, L., Devel, M., De Roeck, A., Dingus, P., Dollfus, C., Dowell, J. D., Dreis, H. B., Drescher, A., Duboc, J., Düllmann, D., Dünger, O., Duhm, H., Ebbinghaus, R., Eberle, M., Ebert, J., Ebert, T. R., Eckerlin, G., Efremenko, V., Egli, S., Eichenberger, S., Eichler, R., Eisele, F., Eisenhandler, E., Ellis, N. N., Ellison, R. J., Elsen, E., Erdmann, M., Evrard, E., Favart, L., Fedotov, A., Feeken, D., Felst, R., Feltesse, J., Fensome, I. F., Ferencei, J., Ferrarotto, F., Flamm, K., Flauger, W., Fleischer, M., Flieser, M., Flügge, G., Fomenko, A., Fominykh, B., Forbush, M., Formánek, J., Foster, J. M., Franke, G., Fretwurst, E., Fuhrmann, P., Gabathuler, E., Gamerdinger, K., Garvey, J., Gayler, J., Gellrich, A., Gennis, M., Genzel, H., Gerhards, R., Godfrey, L., Goerlach, U., Goerlich, L., Gogitidze, N., Goldberg, M., Goodall, A. M., Gorelov, I., Goritchev, P., Grab, C., Grässler, H., Grässler, R., Greenshaw, T., Greif, H., Grindhammer, G., Gruber, C., Haack, J., Haidt, D., Hajduk, L., Hamon, O., Handschuh, D., Hanlon, E. M., Hapke, M., Harjes, J., Haydar, R., Haynes, W. J., Heatherington, J., Hedberg, V., Heinzelmann, G., Henderson, R. C. W., Henschel, H., Herma, R., Herynek, I., Hildesheim, W., Hill, P., Hilton, C. D., Hladký, J., Hoeger, K. C., Huet, Ph., Hufnagel, H., Huot, N., Ibbotson, M., Itterbeck, H., Jabiol, M. -A., Jacholkowska, A., Jacobsson, C., Jaffre, M., Jansen, T., Jönsson, L., Johannsen, K., Johnson, D. P., Johnson, L., Jung, H., Kalmus, P. I. P., Kasarian, S., Kaschowitz, R., Kasselmann, P., Kathage, U., Kaufmann, H. H., Kenyon, I. R., Kermiche, S., Keuker, C., Kiesling, C., Klein, M., Kleinwort, C., Knies, G., Ko, W., Köhler, T., Kolanoski, H., Kole, F., Kolya, S. D., Korbel, V., Korn, M., Kostka, P., Kotelnikov, S. K., Krasny, M. W., Krehbiel, H., Krücker, D., Krüger, U., Kubenka, J. P., Küster, H., Kuhlen, M., Kurča, T., Kurzhöfer, J., Kuznik, B., Lacour, D., Lamarche, F., Lander, R., Landon, M. P. J., Lange, W., Langkau, R., Lanius, P., Laporte, J. F., Lebedev, A., Leuschner, A., Leverenz, C., Levonian, S., Lewin, D., Ley, Ch., Lindner, A., Lindström, G., Linsel, F., Lipinski, J., Loch, P., Lohmander, H., Lopez, G. C., Lüers, D., Magnussen, N., Malinovski, E., Mani, S., Marage, P., Marks, J., Marshall, R., Martens, J., Martin, R., Martyn, H. -U., Martyniak, J., Masson, S., Mavroidis, A., Maxfield, S. J., McMahon, S. J., Mehta, A., Meier, K., Mercer, D., Merz, T., Meyer, C. A., Meyer, H., Meyer, J., Mikocki, S., Milone, V., Monnier, E., Moreau, F., Moreels, J., Morris, J. V., Müller, K., Murín, P., Murray, S. A., Nagovizin, V., Naroska, B., Naumann, Th., Newman, P. R., Newton, D., Neyret, D., Nguyen, H. K., Niebergall, F., Niebuhr, C., Nisius, R., Nowak, G., Noyes, G. W., Nyberg, M., Oberlack, H., Obrock, U., Olsson, J. E., Orenstein, S., Ould-Saada, F., Pascaud, C., Patel, G. D., Peppel, E., Peters, S., Phillips, H. T., Phillips, J. P., Pichler, Ch., Pilgram, W., Pitzl, D., Prell, S., Prosi, R., Rädel, G., Raupach, F., Rauschnabel, K., Reimer, P., Reinshagen, S., Ribarics, P., Riech, V., Riedlberger, J., Riess, S., Rietz, M., Robertson, S. M., Robmann, P., Roosen, R., Rostovtsev, A., Royon, C., Rudowicz, M., Ruffer, M., Rusakov, S., Rybicki, K., Sahlmann, N., Sanchez, E., Sankey, D. P. C., Savitsky, M., Schacht, P., Schleper, P., von Schlippe, W., Schmidt, C., Schmidt, D., Schmitz, W., Schöning, A., Schröder, V., Schulz, M., Schwab, B., Schwind, A., Scobel, W., Seehausen, U., Sell, R., Semenov, A., Shekelyan, V., Sheviakov, I., Shooshtari, H., Shtarkov, L. N., Siegmon, G., Siewert, U., Sirois, Y., Skillicorn, I. O., Smirnov, P., Smith, J. R., Smolik, L., Soloviev, Y., Spitzer, H., Staroba, P., Steenbock, M., Steffen, P., Steinberg, R., Stella, B., Stephens, K., Stier, J., Stösslein, U., Strachota, J., Straumann, U., Struczinski, W., Sutton, J. P., Taylor, R. E., Tchernyshov, V., Thiebaux, C., Thompson, G., Tichomirov, I., Truöl, P., Turnau, J., Tutas, J., Urban, L., Usik, A., Valkar, S., Valkarova, A., Vallée, C., Van Esch, P., Vartapetian, A., Vazdik, Y., Vecko, M., Verrecchia, P., Vick, R., Villet, G., Vogel, E., Wacker, K., Walker, I. W., Walther, A., Weber, G., Wegener, D., Wegner, A., Wellisch, H. P., West, L. R., Willard, S., Winde, M., Winter, G. -G., Wolff, Th., Womersley, L. A., Wright, A. E., Wulff, N., Yiou, T. P., Žáček, J., Závada, P., Zeitnitz, C., Ziaeepour, H., Zimmer, M., Zimmermann, W., Zomer, F., and H1 Collaboration

Published
1994
Full Text
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96. Identification of neurobehavioural symptom groups based on shared brain mechanisms

Author

Ing, A., Samann, P.G., Chu, C., Tay, N., Biondo, F., Robert, G., Jia, T., Wolfers, T., Desrivieres, S., Banaschewski, T., Bokde, A.L., Bromberg, U., Buchel, C., Conrod, P., Fadai, T., Flor, H., Frouin, V., Garavan, H., Spechler, P.A., Gowland, P., Grimmer, Y., Heinz, A., Ittermann, B., Kappel, V., Martinot, J.L., Meyer-Lindenberg, A., Millenet, S., Nees, F., Noort, B. van, Orfanos, D.P., Martinot, M.P., Penttila, J., Poustka, L., Quinlan, E.B., Smolka, M.N., Stringaris, A., Struve, M., Veer, I.M., Walter, H., Whelan, R., Andreassen, O.A., Agartz, I., Lemaitre, H., Barker, E.D., Ashburner, J., Binder, E., Buitelaar, J.K., Marquand, A.F., Robbins, T.W, Schumann, G., Ing, A., Samann, P.G., Chu, C., Tay, N., Biondo, F., Robert, G., Jia, T., Wolfers, T., Desrivieres, S., Banaschewski, T., Bokde, A.L., Bromberg, U., Buchel, C., Conrod, P., Fadai, T., Flor, H., Frouin, V., Garavan, H., Spechler, P.A., Gowland, P., Grimmer, Y., Heinz, A., Ittermann, B., Kappel, V., Martinot, J.L., Meyer-Lindenberg, A., Millenet, S., Nees, F., Noort, B. van, Orfanos, D.P., Martinot, M.P., Penttila, J., Poustka, L., Quinlan, E.B., Smolka, M.N., Stringaris, A., Struve, M., Veer, I.M., Walter, H., Whelan, R., Andreassen, O.A., Agartz, I., Lemaitre, H., Barker, E.D., Ashburner, J., Binder, E., Buitelaar, J.K., Marquand, A.F., Robbins, T.W, and Schumann, G.

Abstract

Item does not contain fulltext, Most psychopathological disorders develop in adolescence. The biological basis for this development is poorly understood. To enhance diagnostic characterization and develop improved targeted interventions, it is critical to identify behavioural symptom groups that share neural substrates. We ran analyses to find relationships between behavioural symptoms and neuroimaging measures of brain structure and function in adolescence. We found two symptom groups, consisting of anxiety/depression and executive dysfunction symptoms, respectively, that correlated with distinct sets of brain regions and inter-regional connections, measured by structural and functional neuroimaging modalities. We found that the neural correlates of these symptom groups were present before behavioural symptoms had developed. These neural correlates showed case-control differences in corresponding psychiatric disorders, depression and attention deficit hyperactivity disorder in independent clinical samples. By characterizing behavioural symptom groups based on shared neural mechanisms, our results provide a framework for developing a classification system for psychiatric illness that is based on quantitative neurobehavioural measures.

Published
2019

97. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author

Czamara, D. (Darina), Eraslan, G. (Goekcen), Page, C. M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hamalainen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Reynolds, R. M. (Rebecca M.), Nystad, W. (Wenche), Haberg, S. E. (Siri E.), London, S. J. (Stephanie J.), O'Donnell, K. J. (Kieran J.), Garg, E. (Elika), Meaney, M. J. (Michael J.), Entringer, S. (Sonja), Wadhwa, P. D. (Pathik D.), Buss, C. (Claudia), Jones, M. J. (Meaghan J.), Lin, D. T. (David T. S.), MacIsaac, J. L. (Julie L.), Kobor, M. S. (Michael S.), Koen, N. (Nastassja), Zar, H. J. (Heather J.), Koenen, K. C. (Karestan C.), Dalvie, S. (Shareefa), Stein, D. J. (Dan J.), Kondofersky, I. (Ivan), Mueller, N. S. (Nikola S.), Theis, F. J. (Fabian J.), Raikkonen, K. (Katri), Binder, E. B. (Elisabeth B.), Wray, N. R. (Naomi R.), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E. M. (Enda M.), Abdellaoui, A. (Abdel), Adams, M. J. (Mark J.), Agerbo, E. (Esben), Air, T. M. (Tracy M.), Andlauer, T. F. (Till F. M.), Bacanu, S.-A. (Silviu-Alin), Baekvad-Hansen, M. (Marie), Beekman, A. T. (Aartjan T. F.), Bigdeli, T. B. (Tim B.), Blackwood, D. H. (Douglas H. R.), Bryois, J. (Julien), Buttenschon, H. N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J. H. (Jane Hvarregaard), Clarke, T.-K. (Toni-Kim), Coleman, J. R. (Jonathan R., I), Colodro-Conde, L. (Lucia), Couvy-Duchesne, B. (Baptiste), Craddock, N. (Nick), Crawford, G. E. (Gregory E.), Davies, G. (Gail), Deary, I. J. (Ian J.), Degenhardt, F. (Franziska), Derks, E. M. (Eske M.), Direk, N. (Nese), Dolan, C. V. (Conor, V), Dunn, E. C. (Erin C.), Eley, T. C. (Thalia C.), Escott-Price, V. (Valentina), Kiadeh, F. F. (Farnush Farhadi Hassan), Finucane, H. K. (Hilary K.), Forstner, A. J. (Andreas J.), Frank, J. (Josef), Gaspar, H. A. (Helena A.), Gill, M. (Michael), Goes, F. S. (Fernando S.), Gordon, S. D. (Scott D.), Grove, J. (Jakob), Hall, L. S. (Lynsey S.), Hansen, C. S. (Christine Soholm), Hansen, T. F. (Thomas F.), Herms, S. (Stefan), Hickie, I. B. (Ian B.), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.-J. (Jouke-Jan), Hougaard, D. M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J. A. (James A.), Kohane, I. S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W. W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltan), Li, Y. (Yihan), Lind, P. A. (Penelope A.), MacIntyre, D. J. (Donald J.), MacKinnon, D. F. (Dean F.), Maier, R. M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H. (Hamdi), McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S. E. (Sarah E.), Mehta, D. (Divya), Middeldorp, C. M. (Christel M.), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F. M. (Francis M.), Montgomery, G. W. (Grant W.), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. G. (Michel G.), Nyholt, D. R. (Dale R.), O'Reilly, P. F. (Paul F.), Oskarsson, H. (Hogni), Owen, M. J. (Michael J.), Painter, J. N. (Jodie N.), Pedersen, C. B. (Carsten Bocker), Pedersen, M. G. (Marianne Girtz), Peterson, R. E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W. J. (Wouter J.), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J. A. (Jorge A.), Qvist, P. (Per), Rice, J. P. (John P.), Riley, B. P. (Brien P.), Rivera, M. (Margarita), Mirza, S. S. (Saira Saeed), Schoevers, R. (Robert), Schulte, E. C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S. I. (Stanley, I), Sigurdsson, E. (Engilbert), Sinnamon, G. C. (Grant C. B.), Smit, J. H. (Johannes H.), Smith, D. J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K. E. (Katherine E.), Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W. (Wesley), Thomson, P. A. (Pippa A.), Thorgeirsson, T. E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A. G. (Andre G.), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A. M. (Albert M.), Viktorin, A. (Alexander), Visscher, P. M. (Peter M.), Wang, Y. (Yunpeng), Webb, B. T. (Bradley T.), Weinsheimer, S. M. (Shantel Marie), Wellmann, J. (Juergen), Willemsen, G. (Gonneke), Witt, S. H. (Stephanie H.), Wu, Y. (Yang), Xi, H. S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B. T. (Bernhard T.), Berger, K. (Klaus), Boomsma, D. I. (Dorret, I), Cichon, S. (Sven), Dannlowski, U. (Udo), de Geus, E. J. (E. J. C.), DePaulo, J. R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tonu), Grabe, H. J. (Hans J.), Hamilton, S. P. (Steven P.), Hayward, C. (Caroline), Heath, A. C. (Andrew C.), Kendler, K. S. (Kenneth S.), Kloiber, S. (Stefan), Lewis, G. (Glyn), Li, Q. S. (Qingqin S.), Lucae, S. (Susanne), Madden, P. A. (Pamela A. F.), Magnusson, P. K. (Patrik K.), Martin, N. G. (Nicholas G.), McIntosh, A. M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P. B. (Preben Bo), Mueller-Myhsok, B. (Bertram), Nordentoft, M. (Merete), Noethen, M. M. (Markus M.), O'Donovan, M. C. (Michael C.), Paciga, S. A. (Sara A.), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W. J. H.), Perlis, R. H. (Roy H.), Porteous, D. J. (David J.), Potash, J. B. (James B.), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T. G. (Thomas G.), Smoller, J. W. (Jordan W.), Stefansson, K. (Kari), Tiemeier, H. (Henning), Uher, R. (Rudolf), Voelzke, H. (Henry), Weissman, M. M. (Myrna M.), Werge, T. (Thomas), Lewis, C. M. (Cathryn M.), Levinson, D. F. (Douglas F.), Breen, G. (Gerome), Borglum, A. D. (Anders D.), Sullivan, P. F. (Patrick F.), Czamara, D. (Darina), Eraslan, G. (Goekcen), Page, C. M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hamalainen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Reynolds, R. M. (Rebecca M.), Nystad, W. (Wenche), Haberg, S. E. (Siri E.), London, S. J. (Stephanie J.), O'Donnell, K. J. (Kieran J.), Garg, E. (Elika), Meaney, M. J. (Michael J.), Entringer, S. (Sonja), Wadhwa, P. D. (Pathik D.), Buss, C. (Claudia), Jones, M. J. (Meaghan J.), Lin, D. T. (David T. S.), MacIsaac, J. L. (Julie L.), Kobor, M. S. (Michael S.), Koen, N. (Nastassja), Zar, H. J. (Heather J.), Koenen, K. C. (Karestan C.), Dalvie, S. (Shareefa), Stein, D. J. (Dan J.), Kondofersky, I. (Ivan), Mueller, N. S. (Nikola S.), Theis, F. J. (Fabian J.), Raikkonen, K. (Katri), Binder, E. B. (Elisabeth B.), Wray, N. R. (Naomi R.), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E. M. (Enda M.), Abdellaoui, A. (Abdel), Adams, M. J. (Mark J.), Agerbo, E. (Esben), Air, T. M. (Tracy M.), Andlauer, T. F. (Till F. M.), Bacanu, S.-A. (Silviu-Alin), Baekvad-Hansen, M. (Marie), Beekman, A. T. (Aartjan T. F.), Bigdeli, T. B. (Tim B.), Blackwood, D. H. (Douglas H. R.), Bryois, J. (Julien), Buttenschon, H. N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J. H. (Jane Hvarregaard), Clarke, T.-K. (Toni-Kim), Coleman, J. R. (Jonathan R., I), Colodro-Conde, L. (Lucia), Couvy-Duchesne, B. (Baptiste), Craddock, N. (Nick), Crawford, G. E. (Gregory E.), Davies, G. (Gail), Deary, I. J. (Ian J.), Degenhardt, F. (Franziska), Derks, E. M. (Eske M.), Direk, N. (Nese), Dolan, C. V. (Conor, V), Dunn, E. C. (Erin C.), Eley, T. C. (Thalia C.), Escott-Price, V. (Valentina), Kiadeh, F. F. (Farnush Farhadi Hassan), Finucane, H. K. (Hilary K.), Forstner, A. J. (Andreas J.), Frank, J. (Josef), Gaspar, H. A. (Helena A.), Gill, M. (Michael), Goes, F. S. (Fernando S.), Gordon, S. D. (Scott D.), Grove, J. (Jakob), Hall, L. S. (Lynsey S.), Hansen, C. S. (Christine Soholm), Hansen, T. F. (Thomas F.), Herms, S. (Stefan), Hickie, I. B. (Ian B.), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.-J. (Jouke-Jan), Hougaard, D. M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J. A. (James A.), Kohane, I. S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W. W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltan), Li, Y. (Yihan), Lind, P. A. (Penelope A.), MacIntyre, D. J. (Donald J.), MacKinnon, D. F. (Dean F.), Maier, R. M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H. (Hamdi), McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S. E. (Sarah E.), Mehta, D. (Divya), Middeldorp, C. M. (Christel M.), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F. M. (Francis M.), Montgomery, G. W. (Grant W.), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. G. (Michel G.), Nyholt, D. R. (Dale R.), O'Reilly, P. F. (Paul F.), Oskarsson, H. (Hogni), Owen, M. J. (Michael J.), Painter, J. N. (Jodie N.), Pedersen, C. B. (Carsten Bocker), Pedersen, M. G. (Marianne Girtz), Peterson, R. E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W. J. (Wouter J.), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J. A. (Jorge A.), Qvist, P. (Per), Rice, J. P. (John P.), Riley, B. P. (Brien P.), Rivera, M. (Margarita), Mirza, S. S. (Saira Saeed), Schoevers, R. (Robert), Schulte, E. C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S. I. (Stanley, I), Sigurdsson, E. (Engilbert), Sinnamon, G. C. (Grant C. B.), Smit, J. H. (Johannes H.), Smith, D. J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K. E. (Katherine E.), Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W. (Wesley), Thomson, P. A. (Pippa A.), Thorgeirsson, T. E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A. G. (Andre G.), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A. M. (Albert M.), Viktorin, A. (Alexander), Visscher, P. M. (Peter M.), Wang, Y. (Yunpeng), Webb, B. T. (Bradley T.), Weinsheimer, S. M. (Shantel Marie), Wellmann, J. (Juergen), Willemsen, G. (Gonneke), Witt, S. H. (Stephanie H.), Wu, Y. (Yang), Xi, H. S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B. T. (Bernhard T.), Berger, K. (Klaus), Boomsma, D. I. (Dorret, I), Cichon, S. (Sven), Dannlowski, U. (Udo), de Geus, E. J. (E. J. C.), DePaulo, J. R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tonu), Grabe, H. J. (Hans J.), Hamilton, S. P. (Steven P.), Hayward, C. (Caroline), Heath, A. C. (Andrew C.), Kendler, K. S. (Kenneth S.), Kloiber, S. (Stefan), Lewis, G. (Glyn), Li, Q. S. (Qingqin S.), Lucae, S. (Susanne), Madden, P. A. (Pamela A. F.), Magnusson, P. K. (Patrik K.), Martin, N. G. (Nicholas G.), McIntosh, A. M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P. B. (Preben Bo), Mueller-Myhsok, B. (Bertram), Nordentoft, M. (Merete), Noethen, M. M. (Markus M.), O'Donovan, M. C. (Michael C.), Paciga, S. A. (Sara A.), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W. J. H.), Perlis, R. H. (Roy H.), Porteous, D. J. (David J.), Potash, J. B. (James B.), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T. G. (Thomas G.), Smoller, J. W. (Jordan W.), Stefansson, K. (Kari), Tiemeier, H. (Henning), Uher, R. (Rudolf), Voelzke, H. (Henry), Weissman, M. M. (Myrna M.), Werge, T. (Thomas), Lewis, C. M. (Cathryn M.), Levinson, D. F. (Douglas F.), Breen, G. (Gerome), Borglum, A. D. (Anders D.), and Sullivan, P. F. (Patrick F.)

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Published
2019

98. 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

99. Genome-wide gene expression in a pharmacological hormonal transition model and its relation to depressive symptoms

Author

Mehta, D., Rex-Haffner, M., Søndergaard, H. B., Pinborg, A., Binder, E. B., Frokjaer, V. G., Mehta, D., Rex-Haffner, M., Søndergaard, H. B., Pinborg, A., Binder, E. B., and Frokjaer, V. G.

Abstract

OBJECTIVES: Sensitivity to sex-steroid hormone fluctuations may increase risk for perinatal depression. We aimed to identify genome-wide biological profiles in women demonstrating sensitivity to pharmacological sex-hormone manipulation with gonadotrophin-releasing hormone agonist (GnRHa).METHODS: Longitudinal gene expression (Illumina Human HT12.v4) and DNA methylation data (Infinium HumanMethylation450K BeadChip) from 60 women (30 GnRHa, 30 placebo) were generated (Trial ID: NCT02661789). Differences between baseline and two follow-up points (initial stimulation- and subsequent early suppression phase) in the biphasic ovarian hormone response to GnRHa were assessed using linear mixed effects models.RESULTS: Genome-wide analysis revealed 588 probes differentially expressed from GnRHa intervention to first stimulatory phase follow-up (intervention group × time) after 10% fdr multiple testing correction. Of these, 54% genes were also significantly associated with estradiol changes over time (proxy for GnRHa response magnitude), 9.5% were associated with changes in depressive symptoms, and 38% were associated with changes in neocortical serotonin transporter binding. The genes were implicated in TGF beta signaling, adipogenesis, regulation of actin cytoskeleton, and focal adhesion pathways and enriched for DNA methylation changes (P = 0.006).CONCLUSIONS: These findings point toward an altered peripheral blood transcriptomic landscape in a pharmacological model of sex-hormone-induced depressive symptoms.

Published
2019

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