Author: "Czamara, D" / Publication Year Range: Last 10 years - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Czamara, D"' showing total 214 results

Start Over Author "Czamara, D" Publication Year Range Last 10 years

214 results on '"Czamara, D"'

1. A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

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

2. Accelerated biological aging during the Covid-19 pandemic – a twinlife epigenetic change satellite study

Author: Schowe, A., primary, Czamara, D., additional, Moenkediek, B., additional, Kuznetsov, D.V., additional, Rohm, T., additional, Instinske, J., additional, Kandler, C., additional, Pahnke, C., additional, Forstner, A., additional, Maj, C., additional, Noethen, M., additional, and Binder, E.B., additional
Published: 2024
Full Text: View/download PDF

3. The P2RX7 polymorphism rs2230912 is associated with depression: A meta-analysis

Author: Czamara, D., Müller-Myhsok, B., and Lucae, S.
Published: 2018
Full Text: View/download PDF

4. Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex

Author: Matosin, N, Arloth, J, Czamara, D, Edmond, KZ, Maitra, M, Froehlich, AS, Martinelli, S, Kaul, D, Bartlett, R, Curry, AR, Gassen, NC, Hafner, K, Mueller, NS, Worf, K, Rehawi, G, Nagy, C, Halldorsdottir, T, Cruceanu, C, Gagliardi, M, Gerstner, N, Koedel, M, Murek, V, Ziller, MJ, Scarr, E, Tao, R, Jaffe, AE, Arzberger, T, Falkai, P, Kleinmann, JE, Weinberger, DR, Mechawar, N, Schmitt, A, Dean, B, Turecki, G, Hyde, TM, Binder, EB, Matosin, N, Arloth, J, Czamara, D, Edmond, KZ, Maitra, M, Froehlich, AS, Martinelli, S, Kaul, D, Bartlett, R, Curry, AR, Gassen, NC, Hafner, K, Mueller, NS, Worf, K, Rehawi, G, Nagy, C, Halldorsdottir, T, Cruceanu, C, Gagliardi, M, Gerstner, N, Koedel, M, Murek, V, Ziller, MJ, Scarr, E, Tao, R, Jaffe, AE, Arzberger, T, Falkai, P, Kleinmann, JE, Weinberger, DR, Mechawar, N, Schmitt, A, Dean, B, Turecki, G, Hyde, TM, and Binder, EB
Abstract: Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical areas of the human brain this occurs. This knowledge is critical to propel FKBP5/1-targeted treatment development. Here, we performed an extensive, large-scale postmortem study (n = 1024) of FKBP5/1, examining neocortical areas (BA9, BA11 and ventral BA24/BA24a) derived from subjects that lived with schizophrenia, major depression or bipolar disorder. With an extensive battery of RNA (bulk RNA sequencing, single-nucleus RNA sequencing, microarray, qPCR, RNAscope) and protein (immunoblot, immunohistochemistry) analysis approaches, we thoroughly investigated the effects of disease state, ageing and genotype on cortical FKBP5/1 expression including in a cell type-specific manner. We identified consistently heightened FKBP5/1 levels in psychopathology and with age, but not genotype, with these effects strongest in schizophrenia. Using single-nucleus RNA sequencing (snRNAseq; BA9 and BA11) and targeted histology (BA9, BA24a), we established that these disease and ageing effects on FKBP5/1 expression were most pronounced in excitatory superficial layer neurons of the neocortex, and this effect appeared to be consistent in both the granular and agranular areas examined. We then found that this increase in FKBP5 levels may impact on synaptic plasticity, as FKBP5 gex levels strongly and inversely correlated with dendritic mushroom spine density and brain-derived neurotrophic factor (BDNF) levels in superficial layer neurons in BA11. These findings pinpoint a novel cellular and molecular m
Published: 2023

5. Maternal exposure to childhood maltreatment and mental and behavioral disorders in children

Author: Airikka, A. (Aino), Lahti-Pulkkinen, M. (Marius), Tuovinen, S. (Soile), Heinonen, K. (Kati), Lahti, J. (Jari), Girchenko, P. (Polina), Lähdepuro, A. (Anna), Pyhälä, R. (Riikka), Czamara, D. (Darina), Villa, P. (Pia), Laivuori, H. (Hannele), Kajantie, E. (Eero), Binder, E. B. (Elisabeth B.), Räikkönen, K. (Katri), Airikka, A. (Aino), Lahti-Pulkkinen, M. (Marius), Tuovinen, S. (Soile), Heinonen, K. (Kati), Lahti, J. (Jari), Girchenko, P. (Polina), Lähdepuro, A. (Anna), Pyhälä, R. (Riikka), Czamara, D. (Darina), Villa, P. (Pia), Laivuori, H. (Hannele), Kajantie, E. (Eero), Binder, E. B. (Elisabeth B.), and Räikkönen, K. (Katri)
Abstract: Exposure to maltreatment in childhood is associated with lifelong risk of mental and behavioral disorders. Whether the effects extend to the next generation remains unclear. We examined whether maternal exposure to childhood abuse and neglect in her own childhood were associated with mental and behavioral disorders and psychiatric symptoms in her children, and whether maternal lifetime mental and behavioral disorders or lower education level mediated or added to the effects. Mothers (n = 2252) of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction cohort study completed the Childhood Trauma Questionnaire and reported on their education and their 7.0–12.1-year-old children’s psychiatric symptoms using the Strengths and Difficulties Questionnaire. We identified lifetime mental and behavioral disorder diagnoses for the mothers and diagnoses for their children from birth (2006–2010) until 8.4–12.8 years (12/31/2018) from Care Register for Health Care. We found that maternal exposure to childhood abuse, but not neglect, was associated with higher hazards of mental and behavioral disorders (hazard ratio 1.20, 95% confidence interval 1.06–1.37) in children. These associations were partially mediated by maternal mental and behavioral disorders and education (proportion of effect size mediated: 23.8% and 15.1%, respectively), which together with maternal exposure to childhood abuse added to the hazard of mental and behavioral disorders in children. Similar associations were found for maternal exposure to childhood abuse and neglect with psychiatric symptoms in children. To conclude, maternal exposure to childhood maltreatment is associated with mental and behavioral disorders and psychiatric symptoms in children. Our findings call for interventions to prevent intergenerational transmission.
Published: 2023

6. 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

7. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Author: Kotsakis Ruehlmann, A., Sammallahti, S., Cortés Hidalgo, A.P., Bakulski, K.M., Binder, E.B., Campbell, M.L., Caramaschi, D., Cecil, C., Colicino, E., Cruceanu, C., Czamara, D., Dieckmann, L., Dou, J., Felix, J.F., Frank, J., Håberg, S.E., Herberth, Gunda, Hoang, T.T., Houtepen, L.C., Hüls, A., Koen, N., London, S.J., Magnus, M.C., Mancano, G., Mulder, R.H., Page, C.M., Räikkönen, K., Röder, Stefan, Schmidt, R.J., Send, T.S., Sharp, G., Stein, D.J., Streit, F., Tuhkanen, J., Witt, S.H., Zar, H.J., Zenclussen, Ana Claudia, Zhang, Y., Zillich, L., Wright, R., Lahti, J., Brunst, K.J., Kotsakis Ruehlmann, A., Sammallahti, S., Cortés Hidalgo, A.P., Bakulski, K.M., Binder, E.B., Campbell, M.L., Caramaschi, D., Cecil, C., Colicino, E., Cruceanu, C., Czamara, D., Dieckmann, L., Dou, J., Felix, J.F., Frank, J., Håberg, S.E., Herberth, Gunda, Hoang, T.T., Houtepen, L.C., Hüls, A., Koen, N., London, S.J., Magnus, M.C., Mancano, G., Mulder, R.H., Page, C.M., Räikkönen, K., Röder, Stefan, Schmidt, R.J., Send, T.S., Sharp, G., Stein, D.J., Streit, F., Tuhkanen, J., Witt, S.H., Zar, H.J., Zenclussen, Ana Claudia, Zhang, Y., Zillich, L., Wright, R., Lahti, J., and Brunst, K.J.
Abstract: Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biologic mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve datasets from ten pregnancy cohorts (N=5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
Published: 2023

8. 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

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

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

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

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

11. Genome-wide copy number variant and high-throughput transcriptomics analyses of placental tissues underscore persisting child susceptibility in at-risk pregnancies cleared in standard genetic testing

Author: Czamara, D. (Darina), Cruceanu, C. (Cristiana), Lahti-Pulkkinen, M. (Marius), Dieckmann, L. (Linda), Ködel, M. (Maik), Sauer, S. (Susann), Rex-Haffner, M. (Monika), Sammallahti, S. (Sara), Kajantie, E. (Eero), Laivuori, H. (Hannele), Lahti, J. (Jari), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), Czamara, D. (Darina), Cruceanu, C. (Cristiana), Lahti-Pulkkinen, M. (Marius), Dieckmann, L. (Linda), Ködel, M. (Maik), Sauer, S. (Susann), Rex-Haffner, M. (Monika), Sammallahti, S. (Sara), Kajantie, E. (Eero), Laivuori, H. (Hannele), Lahti, J. (Jari), Räikkönen, K. (Katri), and Binder, E. B. (Elisabeth B.)
Abstract: Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22–13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and
Published: 2022

12. A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Author: Fernandez-Jimenez, N, Fore, R, Cilleros-Portet, A, Lepeule, J, Perron, P, Kvist, T, Tian, F-Y, Lesseur, C, Binder, AM, Lozano, M, Martorell-Marugan, J, Loke, YJ, Bakulski, KM, Zhu, Y, Forhan, A, Sammallahti, S, Everson, TM, Chen, J, Michels, KB, Belmonte, T, Carmona-Saez, P, Halliday, J, Fallin, MD, LaSalle, JM, Tost, J, Czamara, D, Fernandez, MF, Gomez-Martin, A, Craig, JM, Gonzalez-Alzaga, B, Schmidt, RJ, Dou, JF, Muggli, E, Lacasana, M, Vrijheid, M, Marsit, CJ, Karagas, MR, Raikkonen, K, Bouchard, L, Heude, B, Santa-Marina, L, Bustamante, M, Hivert, M-F, Bilbao, JR, Fernandez-Jimenez, N, Fore, R, Cilleros-Portet, A, Lepeule, J, Perron, P, Kvist, T, Tian, F-Y, Lesseur, C, Binder, AM, Lozano, M, Martorell-Marugan, J, Loke, YJ, Bakulski, KM, Zhu, Y, Forhan, A, Sammallahti, S, Everson, TM, Chen, J, Michels, KB, Belmonte, T, Carmona-Saez, P, Halliday, J, Fallin, MD, LaSalle, JM, Tost, J, Czamara, D, Fernandez, MF, Gomez-Martin, A, Craig, JM, Gonzalez-Alzaga, B, Schmidt, RJ, Dou, JF, Muggli, E, Lacasana, M, Vrijheid, M, Marsit, CJ, Karagas, MR, Raikkonen, K, Bouchard, L, Heude, B, Santa-Marina, L, Bustamante, M, Hivert, M-F, and Bilbao, JR
Abstract: Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.
Published: 2022

13. Cohort profile:InTraUterine sampling in early pregnancy (ITU), a prospective pregnancy cohort study in Finland:study design and baseline characteristics

Author: Kvist, T. (Tuomas), Sammallahti, S. (Sara), Lahti-Pulkkinen, M. (Marius), Cruceanu, C. (Cristiana), Czamara, D. (Darina), Dieckmann, L. (Linda), Tontsch, A. (Alina), Röh, S. (Simone), Rex-Haffner, M. (Monika), Wolford, E. (Eiina), Reynolds, R. (Rebecca), Eriksson, J. (Johan), Suomalainen-König, S. (Sanna), Laivuori, H. (Hannele), Kajantie, E. (Eero), Lahdensuo, E. (Eija), Binder, E. (Elisabeth), Räikkönen, K. (Katri), Kvist, T. (Tuomas), Sammallahti, S. (Sara), Lahti-Pulkkinen, M. (Marius), Cruceanu, C. (Cristiana), Czamara, D. (Darina), Dieckmann, L. (Linda), Tontsch, A. (Alina), Röh, S. (Simone), Rex-Haffner, M. (Monika), Wolford, E. (Eiina), Reynolds, R. (Rebecca), Eriksson, J. (Johan), Suomalainen-König, S. (Sanna), Laivuori, H. (Hannele), Kajantie, E. (Eero), Lahdensuo, E. (Eija), Binder, E. (Elisabeth), and Räikkönen, K. (Katri)
Abstract: Purpose: The InTraUterine sampling in early pregnancy (ITU) is a prospective pregnancy cohort study. The overarching aim of ITU is to unravel genomic, epigenomic, transcriptomic, endocrine, inflammatory and metabolic maternal-placental-fetal mechanisms involved in the programming of health and disease after exposure to prenatal environmental adversity, such as maternal malnutrition, cardiometabolic disorders, infections, medical interventions, mental disorders and psychosocial stress. This paper describes the study protocol, design and baseline characteristics of the cohort. Participants: We included 944 pregnant Finnish women, their partners and children born alive between April 2012 and December 2017. The women were recruited through the national, voluntary trisomy 21 screening between 9+0 and 21+6 gestational weeks. Of the participating women, 543 were screen positive and underwent fetal chromosomal testing. Test result of these women suggested no fetal chromosomal abnormality. Further, we recruited 401 women who were screen negative and who did not undergo fetal chromosomal testing. Findings to date: We have collected chorionic villi and amniotic fluid from the screen-positive women; blood, urine, buccal swabs and diurnal salivary samples from all women; blood and buccal swabs from all partners; and placenta, cord blood and buccal swabs from all newborns for analyses of the genome, epigenome, transcriptome, and endocrine, inflammatory and metabolic markers. These data are coupled with comprehensive phenotypes, including questions on demographic characteristics, health and well-being of the women and their partners during pregnancy and of the women and their children at the child’s age of 1.7 and 3 years. Data also come from patient records and nationwide registers covering health, lifestyle and medication data. Future plans: Multiple layers of ITU data allow integrative data analyses, which translate to biomarker identification and allow risk stratifica
Published: 2022

14. Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies

Author: Dieckmann, L. (Linda), Cruceanu, C. (Cristiana), Lahti-Pulkkinen, M. (Marius), Lahti, J. (Jari), Kvist, T. (Tuomas), Laivuori, H. (Hannele), Sammallahti, S. (Sara), Villa, P. M. (Pia M.), Suomalainen-König, S. (Sanna), Rancourt, R. C. (Rebecca C.), Plagemann, A. (Andreas), Henrich, W. (Wolfgang), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Entringer, S. (Sonja), Braun, T. (Thorsten), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), Czamara, D. (Darina), Dieckmann, L. (Linda), Cruceanu, C. (Cristiana), Lahti-Pulkkinen, M. (Marius), Lahti, J. (Jari), Kvist, T. (Tuomas), Laivuori, H. (Hannele), Sammallahti, S. (Sara), Villa, P. M. (Pia M.), Suomalainen-König, S. (Sanna), Rancourt, R. C. (Rebecca C.), Plagemann, A. (Andreas), Henrich, W. (Wolfgang), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Entringer, S. (Sonja), Braun, T. (Thorsten), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), and Czamara, D. (Darina)
Abstract: The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.
Published: 2022

15. Maternal haemoglobin levels in pregnancy and child DNA methylation:a study in the pregnancy and childhood epigenetics consortium

Author: Ronkainen, J. (Justiina), Heiskala, A. (Anni), Vehmeijer, F. O. (Florianne O. L.), Lowry, E. (Estelle), Caramaschi, D. (Doretta), Estrada Gutierrez, G. (Guadalupe), Heiss, J. A. (Jonathan A.), Hummel, N. (Nadine), Keikkala, E. (Elina), Kvist, T. (Tuomas), Kupsco, A. (Allison), Melton, P. E. (Phillip E.), Pesce, G. (Giancarlo), Soomro, M. H. (Munawar H.), Vives-Usano, M. (Marta), Baiz, N. (Nour), Binder, E. (Elisabeth), Czamara, D. (Darina), Guxens, M. (Mònica), Mustaniemi, S. (Sanna), London, S. J. (Stephanie J.), Rauschert, S. (Sebastian), Vääräsmäki, M. (Marja), Vrijheid, M. (Martine), Ziegler, A.-G. (Anette-G.), Annesi-Maesano, I. (Isabella), Bustamante, M. (Mariona), Huang, R.-C. (Rae-Chi), Hummel, S. (Sandra), Just, A. C. (Allan C.), Kajantie, E. (Eero), Lahti, J. (Jari), Lawlor, D. (Deborah), Räikkönen, K. (Katri), Järvelin, M.-R. (Marjo-Riitta), Felix, J. F. (Janine F.), Sebert, S. (Sylvain), Ronkainen, J. (Justiina), Heiskala, A. (Anni), Vehmeijer, F. O. (Florianne O. L.), Lowry, E. (Estelle), Caramaschi, D. (Doretta), Estrada Gutierrez, G. (Guadalupe), Heiss, J. A. (Jonathan A.), Hummel, N. (Nadine), Keikkala, E. (Elina), Kvist, T. (Tuomas), Kupsco, A. (Allison), Melton, P. E. (Phillip E.), Pesce, G. (Giancarlo), Soomro, M. H. (Munawar H.), Vives-Usano, M. (Marta), Baiz, N. (Nour), Binder, E. (Elisabeth), Czamara, D. (Darina), Guxens, M. (Mònica), Mustaniemi, S. (Sanna), London, S. J. (Stephanie J.), Rauschert, S. (Sebastian), Vääräsmäki, M. (Marja), Vrijheid, M. (Martine), Ziegler, A.-G. (Anette-G.), Annesi-Maesano, I. (Isabella), Bustamante, M. (Mariona), Huang, R.-C. (Rae-Chi), Hummel, S. (Sandra), Just, A. C. (Allan C.), Kajantie, E. (Eero), Lahti, J. (Jari), Lawlor, D. (Deborah), Räikkönen, K. (Katri), Järvelin, M.-R. (Marjo-Riitta), Felix, J. F. (Janine F.), and Sebert, S. (Sylvain)
Abstract: Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.
Published: 2022

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

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

17. The interplay of childhood maltreatment and lifetime stress with epigenetic age acceleration in psychiatric disease

Author: Yusupov, N., Sauer, S., Ködel, M., Rex-Haffner, M., Dieckmann, L., Kopf-Beck, J., BeCOME working group, T., OPTIMA working group, T., Brückl, T.M., Czamara, D., and Binder, E.B.
Published: 2022
Full Text: View/download PDF

18. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author: Dongen, J. Van, Hagenbeek, F.A., Suderman, M., Roetman, P.J., Sugden, K., Chiocchetti, A.G., Ismail, K., Mulder, R.H., Hafferty, J.D., Adams, M.J., Walker, R.M., Morris, S.W., Lahti, J., Küpers, L.K., Escaramis, G., Alemany, S., Bonder, M. Jan, Meijer, M., Ip, H.F., Jansen, R., Baselmans, B.M.L., Parmar, P., Lowry, E., Streit, F., Sirignano, L., Send, T.S., Frank, J., Jylhävä, J., Wang, Y., Mishra, P.P., Colins, O.F., Corcoran, D.L., Poulton, R., Mill, J., Hannon, E., Arseneault, L., Korhonen, T., Vuoksimaa, E., Felix, J.F., Bakermans-Kranenburg, M.J., Campbell, A., Czamara, D., Binder, E., Corpeleijn, E., Gonzalez, J.R., Grazuleviciene, R., Gutzkow, K.B., Evandt, J., Vafeiadi, M., Klein, M., Meer, D. van der, Ligthart, L., Kluft, C., Davies, G.E., Hakulinen, C., Keltikangas-Järvinen, L., Franke, B., Freitag, C.M., Konrad, K., Hervas, A., Fernández-Rivas, A., Vetro, A., Raitakari, O., Lehtimäki, T., Vermeiren, R., Strandberg, T., Räikkönen, K., Snieder, H., Witt, S.H., Deuschle, M., Pedersen, N.L., Hägg, S., Sunyer, J., Franke, L., Kaprio, J., Ollikainen, M., Moffitt, T.E., Tiemeier, H., van, I.M.H., Relton, C., Vrijheid, M., Sebert, S., Jarvelin, M.R., Caspi, A., Evans, K.L., McIntosh, A.M., Bartels, M., Boomsma, D.I., Dongen, J. Van, Hagenbeek, F.A., Suderman, M., Roetman, P.J., Sugden, K., Chiocchetti, A.G., Ismail, K., Mulder, R.H., Hafferty, J.D., Adams, M.J., Walker, R.M., Morris, S.W., Lahti, J., Küpers, L.K., Escaramis, G., Alemany, S., Bonder, M. Jan, Meijer, M., Ip, H.F., Jansen, R., Baselmans, B.M.L., Parmar, P., Lowry, E., Streit, F., Sirignano, L., Send, T.S., Frank, J., Jylhävä, J., Wang, Y., Mishra, P.P., Colins, O.F., Corcoran, D.L., Poulton, R., Mill, J., Hannon, E., Arseneault, L., Korhonen, T., Vuoksimaa, E., Felix, J.F., Bakermans-Kranenburg, M.J., Campbell, A., Czamara, D., Binder, E., Corpeleijn, E., Gonzalez, J.R., Grazuleviciene, R., Gutzkow, K.B., Evandt, J., Vafeiadi, M., Klein, M., Meer, D. van der, Ligthart, L., Kluft, C., Davies, G.E., Hakulinen, C., Keltikangas-Järvinen, L., Franke, B., Freitag, C.M., Konrad, K., Hervas, A., Fernández-Rivas, A., Vetro, A., Raitakari, O., Lehtimäki, T., Vermeiren, R., Strandberg, T., Räikkönen, K., Snieder, H., Witt, S.H., Deuschle, M., Pedersen, N.L., Hägg, S., Sunyer, J., Franke, L., Kaprio, J., Ollikainen, M., Moffitt, T.E., Tiemeier, H., van, I.M.H., Relton, C., Vrijheid, M., Sebert, S., Jarvelin, M.R., Caspi, A., Evans, K.L., McIntosh, A.M., Bartels, M., and Boomsma, D.I.
Abstract: Item does not contain fulltext, DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Published: 2021

19. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author: Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), Boomsma, D.I. (Dorret I.), Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), and Boomsma, D.I. (Dorret I.)
Abstract: DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48
Published: 2021
Full Text: View/download PDF

20. Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium

Author: Ronkainen, J. (Justiina), Heiskala, A. (Anni), Vehmeijer, F.O.L. (Florianne O.L.), Lowry, E. (Estelle), Caramaschi, D. (Doretta), Estrada Gutierrez, G. (Guadalupe), Heiss, J.A. (Jonathan A.), Hummel, N. (Nadine), Keikkala, E. (Elina), Kvist, T. (Tuomas), Kupsco, A. (Allison), Melton, P.E. (Phillip E.), Pesce, G. (Giancarlo), Soomro, M.H. (Munawar H.), Vives-Usano, M. (Marta), Baïz, N. (Nour), Binder, E.B. (Elisabeth), Czamara, D. (Darina), Guxens Junyent, M. (Mònica), Mustaniemi, S. (Sanna), London, S.J. (Stephanie J.), Rauschert, S. (Sebastian), Vääräsmäki, M. (Marja), Vrijheid, M. (Martine), Ziegler, A.-G. (Anette-G.), Annesi-Maesano, I. (Isabella), Bustamante, M. (Mariona), Huang, R.-C. (Rae-Chi), Hummel, S. (Sandra), Just, A.C. (Allan C.), Kajantie, E. (Eero), Lahti, J. (Jari), Lawlor, D. (Deborah), Räikkönen, K. (Katri), Järvelin, M.-R. (Marjo-Riitta), Felix, J.F. (Janine), Sebert, S. (Sylvain), Ronkainen, J. (Justiina), Heiskala, A. (Anni), Vehmeijer, F.O.L. (Florianne O.L.), Lowry, E. (Estelle), Caramaschi, D. (Doretta), Estrada Gutierrez, G. (Guadalupe), Heiss, J.A. (Jonathan A.), Hummel, N. (Nadine), Keikkala, E. (Elina), Kvist, T. (Tuomas), Kupsco, A. (Allison), Melton, P.E. (Phillip E.), Pesce, G. (Giancarlo), Soomro, M.H. (Munawar H.), Vives-Usano, M. (Marta), Baïz, N. (Nour), Binder, E.B. (Elisabeth), Czamara, D. (Darina), Guxens Junyent, M. (Mònica), Mustaniemi, S. (Sanna), London, S.J. (Stephanie J.), Rauschert, S. (Sebastian), Vääräsmäki, M. (Marja), Vrijheid, M. (Martine), Ziegler, A.-G. (Anette-G.), Annesi-Maesano, I. (Isabella), Bustamante, M. (Mariona), Huang, R.-C. (Rae-Chi), Hummel, S. (Sandra), Just, A.C. (Allan C.), Kajantie, E. (Eero), Lahti, J. (Jari), Lawlor, D. (Deborah), Räikkönen, K. (Katri), Järvelin, M.-R. (Marjo-Riitta), Felix, J.F. (Janine), and Sebert, S. (Sylvain)
Abstract: Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.
Published: 2021
Full Text: View/download PDF

21. DNA methylation signatures of aggression and closely related constructs:a meta-analysis of epigenome-wide studies across the lifespan

Author: van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), Boomsma, D. I. (Dorret, I), van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), and Boomsma, D. I. (Dorret, I)
Abstract: DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Published: 2021

22. Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation

Author: Czamara, D. (Darina), Dieckmann, L. (Linda), Röh, S. (Simone), Kraemer, S. (Sarah), Rancourt, R. C. (Rebecca C.), Sammallahti, S. (Sara), Kajantie, E. (Eero), Laivuori, H. (Hannele), Eriksson, J. G. (Johan G.), Räikkönen, K. (Katri), Henrich, W. (Wolfgang), Plagemann, A. (Andreas), Binder, E. B. (Elisabeth B.), Braun, T. (Thorsten), Entringer, S. (Sonja), Czamara, D. (Darina), Dieckmann, L. (Linda), Röh, S. (Simone), Kraemer, S. (Sarah), Rancourt, R. C. (Rebecca C.), Sammallahti, S. (Sara), Kajantie, E. (Eero), Laivuori, H. (Hannele), Eriksson, J. G. (Johan G.), Räikkönen, K. (Katri), Henrich, W. (Wolfgang), Plagemann, A. (Andreas), Binder, E. B. (Elisabeth B.), Braun, T. (Thorsten), and Entringer, S. (Sonja)
Abstract: Background: Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results: We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions: Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.
Published: 2021

23. Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Author: Sammallahti, S. (Sara), Cortes Hidalgo, A. P. (Andrea P.), Tuominen, S. (Samuli), Malmberg, A. (Anni), Mulder, R. H. (Rosa H.), Brunst, K. J. (Kelly J.), Alemany, S. (Silvia), McBride, N. S. (Nancy S.), Yousefi, P. (Paul), Heiss, J. A. (Jonathan A.), McRae, N. (Nia), Page, C. M. (Christian M.), Jin, J. (Jianping), Pesce, G. (Giancarlo), Caramaschi, D. (Doretta), Rifas-Shiman, S. L. (Sheryl L.), Koen, N. (Nastassja), Adams, C. D. (Charleen D.), Magnus, M. C. (Maria C.), Baiz, N. (Nour), Ratanatharathorn, A. (Andrew), Czamara, D. (Darina), Haberg, S. E. (Siri E.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Cardenas, A. (Andres), DeMeo, D. L. (Dawn L.), Lawlor, D. A. (Deborah A.), Relton, C. L. (Caroline L.), Felix, J. F. (Janine F.), van IJzendoorn, M. H. (Marinus H.), Bakermans-Kranenburg, M. J. (Marian J.), Kajantie, E. (Eero), Raikkonen, K. (Katri), Sunyer, J. (Jordi), Sharp, G. C. (Gemma C.), Houtepen, L. C. (Lotte C.), Nohr, E. A. (Ellen A.), Sorensen, T. I. (Thorkild I. A.), Tellez-Rojo, M. M. (Martha M.), Wright, R. O. (Robert O.), Annesi-Maesano, I. (Isabella), Wright, J. (John), Hivert, M.-F. (Marie-France), Wright, R. J. (Rosalind J.), Zar, H. J. (Heather J.), Stein, D. J. (Dan J.), London, S. J. (Stephanie J.), Cecil, C. A. (Charlotte A. M.), Tiemeier, H. (Henning), Lahti, J. (Jari), Sammallahti, S. (Sara), Cortes Hidalgo, A. P. (Andrea P.), Tuominen, S. (Samuli), Malmberg, A. (Anni), Mulder, R. H. (Rosa H.), Brunst, K. J. (Kelly J.), Alemany, S. (Silvia), McBride, N. S. (Nancy S.), Yousefi, P. (Paul), Heiss, J. A. (Jonathan A.), McRae, N. (Nia), Page, C. M. (Christian M.), Jin, J. (Jianping), Pesce, G. (Giancarlo), Caramaschi, D. (Doretta), Rifas-Shiman, S. L. (Sheryl L.), Koen, N. (Nastassja), Adams, C. D. (Charleen D.), Magnus, M. C. (Maria C.), Baiz, N. (Nour), Ratanatharathorn, A. (Andrew), Czamara, D. (Darina), Haberg, S. E. (Siri E.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Cardenas, A. (Andres), DeMeo, D. L. (Dawn L.), Lawlor, D. A. (Deborah A.), Relton, C. L. (Caroline L.), Felix, J. F. (Janine F.), van IJzendoorn, M. H. (Marinus H.), Bakermans-Kranenburg, M. J. (Marian J.), Kajantie, E. (Eero), Raikkonen, K. (Katri), Sunyer, J. (Jordi), Sharp, G. C. (Gemma C.), Houtepen, L. C. (Lotte C.), Nohr, E. A. (Ellen A.), Sorensen, T. I. (Thorkild I. A.), Tellez-Rojo, M. M. (Martha M.), Wright, R. O. (Robert O.), Annesi-Maesano, I. (Isabella), Wright, J. (John), Hivert, M.-F. (Marie-France), Wright, R. J. (Rosalind J.), Zar, H. J. (Heather J.), Stein, D. J. (Dan J.), London, S. J. (Stephanie J.), Cecil, C. A. (Charlotte A. M.), Tiemeier, H. (Henning), and Lahti, J. (Jari)
Abstract: Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.
Published: 2021

24. Characteristics of epigenetic aging across gestational and perinatal tissues

Author: Dieckmann, L. (Linda), Lahti-Pulkkinen, M. (Marius), Kvist, T. (Tuomas), Lahti, J. (Jari), DeWitt, P. E. (Peter E.), Cruceanu, C. (Cristiana), Laivuori, H. (Hannele), Sammallahti, S. (Sara), Villa, P. M. (Pia M.), Suomalainen-König, S. (Sanna), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), Czamara, D. (Darina), Dieckmann, L. (Linda), Lahti-Pulkkinen, M. (Marius), Kvist, T. (Tuomas), Lahti, J. (Jari), DeWitt, P. E. (Peter E.), Cruceanu, C. (Cristiana), Laivuori, H. (Hannele), Sammallahti, S. (Sara), Villa, P. M. (Pia M.), Suomalainen-König, S. (Sanna), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), and Czamara, D. (Darina)
Abstract: Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself
Published: 2021

25. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.

Author: UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, Alarcón-Riquelme, Marta, UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, and Alarcón-Riquelme, Marta
Abstract: Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
Published: 2021

26. 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

27. 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
Full Text: View/download PDF

28. Cord blood DNA methylation reflects cord blood C-reactive protein levels but not maternal levels: a longitudinal study and meta-analysis

Author: Yeung, E.H. (Edwina H.), Guan, W. (Weihua), Zeng, X. (Xuehuo), Salas, L.A. (Lucas A.), Mumford, S.L. (Sunni L.), de Prado Bert, P. (Paula), Meel, E.R. (Evelien) van, Malmberg, A. (Anni), Sunyer, J. (Jordi), Duijts, L. (Liesbeth), Felix, J.F. (Janine), Czamara, D. (Darina), Hämäläinen, E. (Esa), Binder, E.B. (Elisabeth), Räikkönen, K. (Katri), Lahti, J. (Jari), London, S.J. (Stephanie J.), Silver, R.M. (Robert M.), Schisterman, E.F. (Enrique F.), Yeung, E.H. (Edwina H.), Guan, W. (Weihua), Zeng, X. (Xuehuo), Salas, L.A. (Lucas A.), Mumford, S.L. (Sunni L.), de Prado Bert, P. (Paula), Meel, E.R. (Evelien) van, Malmberg, A. (Anni), Sunyer, J. (Jordi), Duijts, L. (Liesbeth), Felix, J.F. (Janine), Czamara, D. (Darina), Hämäläinen, E. (Esa), Binder, E.B. (Elisabeth), Räikkönen, K. (Katri), Lahti, J. (Jari), London, S.J. (Stephanie J.), Silver, R.M. (Robert M.), and Schisterman, E.F. (Enrique F.)
Abstract: BACKGROUND: Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. RESULTS: Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in cord blood. The t
Published: 2020
Full Text: View/download PDF

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

Author: Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Melén, E. (Erik), Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), and Melén, E. (Erik)
Abstract: BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
Published: 2020
Full Text: View/download PDF

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

Author: Merid, SK, Novoloaca, A, Sharp, GC, Kupers, LK, Kho, AT, Roy, R, Gao, L, Annesi-Maesano, I, Jain, P, Plusquin, M, Kogevinas, M, Allard, C, Vehmeijer, FO, Kazmi, N, Salas, LA, Rezwan, FI, Zhang, H, Sebert, S, Czamara, D, Rifas-Shiman, SL, Melton, PE, Lawlor, DA, Pershagen, G, Breton, CV, Huen, K, Baiz, N, Gagliardi, L, Nawrot, TS, Corpeleijn, E, Perron, P, Duijts, L, Nohr, EA, Bustamante, M, Ewart, SL, Karmaus, W, Zhao, S, Page, CM, Herceg, Z, Jarvelin, M-R, Lahti, J, Baccarelli, AA, Anderson, D, Kachroo, P, Relton, CL, Bergstrom, A, Eskenazi, B, Soomro, MH, Vineis, P, Snieder, H, Bouchard, L, Jaddoe, VW, Sorensen, TIA, Vrijheid, M, Arshad, SH, Holloway, JW, Haberg, SE, Magnus, P, Dwyer, T, Binder, EB, DeMeo, DL, Vonk, JM, Newnham, J, Tantisira, KG, Kull, I, Wiemels, JL, Heude, B, Sunyer, J, Nystad, W, Munthe-Kaas, MC, Raikkonen, K, Oken, E, Huang, R-C, Weiss, ST, Anto, JM, Bousquet, J, Kumar, A, Soderhall, C, Almqvist, C, Cardenas, A, Gruzieva, O, Xu, C-J, Reese, SE, Kere, J, Brodin, P, Solomon, O, Wielscher, M, Holland, N, Ghantous, A, Hivert, M-F, Felix, JF, Koppelman, GH, London, SJ, Melen, E, Merid, SK, Novoloaca, A, Sharp, GC, Kupers, LK, Kho, AT, Roy, R, Gao, L, Annesi-Maesano, I, Jain, P, Plusquin, M, Kogevinas, M, Allard, C, Vehmeijer, FO, Kazmi, N, Salas, LA, Rezwan, FI, Zhang, H, Sebert, S, Czamara, D, Rifas-Shiman, SL, Melton, PE, Lawlor, DA, Pershagen, G, Breton, CV, Huen, K, Baiz, N, Gagliardi, L, Nawrot, TS, Corpeleijn, E, Perron, P, Duijts, L, Nohr, EA, Bustamante, M, Ewart, SL, Karmaus, W, Zhao, S, Page, CM, Herceg, Z, Jarvelin, M-R, Lahti, J, Baccarelli, AA, Anderson, D, Kachroo, P, Relton, CL, Bergstrom, A, Eskenazi, B, Soomro, MH, Vineis, P, Snieder, H, Bouchard, L, Jaddoe, VW, Sorensen, TIA, Vrijheid, M, Arshad, SH, Holloway, JW, Haberg, SE, Magnus, P, Dwyer, T, Binder, EB, DeMeo, DL, Vonk, JM, Newnham, J, Tantisira, KG, Kull, I, Wiemels, JL, Heude, B, Sunyer, J, Nystad, W, Munthe-Kaas, MC, Raikkonen, K, Oken, E, Huang, R-C, Weiss, ST, Anto, JM, Bousquet, J, Kumar, A, Soderhall, C, Almqvist, C, Cardenas, A, Gruzieva, O, Xu, C-J, Reese, SE, Kere, J, Brodin, P, Solomon, O, Wielscher, M, Holland, N, Ghantous, A, Hivert, M-F, Felix, JF, Koppelman, GH, London, SJ, and Melen, E
Abstract: BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
Published: 2020

31. Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression

Author: Hagenaars, SP, Coleman, JR, Choi, SW, Gaspar, H, Adams, MJ, Howard, DM, Hodgson, K, Traylor, M, Air, TM, Andlauer, TFM, Arolt, V, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Campbell, A, Cearns, M, Czamara, D, Dannlowski, U, Domschke, K, de Geus, EJC, Hamilton, SP, Hayward, C, Hickie, IB, Hottenga, JJ, Ising, M, Jones, I, Jones, L, Kutalik, Z, Lucae, S, Martin, NG, Milaneschi, Y, Mueller-Myhsok, B, Owen, MJ, Padmanabhan, S, Penninx, BWJH, Pistis, G, Porteous, DJ, Preisig, M, Ripke, S, Shyn, S, Sullivan, PF, Whitfield, JB, Wray, NR, McIntosh, AM, Deary, IJ, Breen, G, Lewis, CM, Hagenaars, SP, Coleman, JR, Choi, SW, Gaspar, H, Adams, MJ, Howard, DM, Hodgson, K, Traylor, M, Air, TM, Andlauer, TFM, Arolt, V, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Campbell, A, Cearns, M, Czamara, D, Dannlowski, U, Domschke, K, de Geus, EJC, Hamilton, SP, Hayward, C, Hickie, IB, Hottenga, JJ, Ising, M, Jones, I, Jones, L, Kutalik, Z, Lucae, S, Martin, NG, Milaneschi, Y, Mueller-Myhsok, B, Owen, MJ, Padmanabhan, S, Penninx, BWJH, Pistis, G, Porteous, DJ, Preisig, M, Ripke, S, Shyn, S, Sullivan, PF, Whitfield, JB, Wray, NR, McIntosh, AM, Deary, IJ, Breen, G, and Lewis, CM
Abstract: It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.
Published: 2020

32. 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

33. 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

34. 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

35. Cord blood DNA methylation reflects cord blood C-reactive protein levels but not maternal levels: a longitudinal study and meta-analysis

Author: Yeung, EWH, Guan, WH, Zeng, XH, Salas, LA, Mumford, SL, Bert, PD, van Meel, ER, Malmberg, A, Sunyer, J, Duijts, Liesbeth, Felix, Janine, Czamara, D, Hamalainen, E, Binder, EB, Raikkonen, K, Lahti, J, London, SJ, Silver, RM, Schisterman, EF, Yeung, EWH, Guan, WH, Zeng, XH, Salas, LA, Mumford, SL, Bert, PD, van Meel, ER, Malmberg, A, Sunyer, J, Duijts, Liesbeth, Felix, Janine, Czamara, D, Hamalainen, E, Binder, EB, Raikkonen, K, Lahti, J, London, SJ, Silver, RM, and Schisterman, EF
Published: 2020

36. 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

37. 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

38. 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

39. Polygenic Risk Score Approaches for Methylation Data in Multi-Ethnic Populations

Author: Huels, A., primary, Gatev, E., additional, Czamara, D., additional, Conneely, K.N., additional, Koen, N., additional, Zar, H.J., additional, Stein, D.J., additional, Epstein, M.P., additional, and Kobor, M.S., additional
Published: 2020
Full Text: View/download PDF

40. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns:Findings From the Pregnancy and Childhood Epigenetics Consortium

Author: Kazmi, N, Sharp, GC, Reese, SE, Vehmeijer, FO, Lahti, J, Page, CM, Zhang, WM, Rifas-Shiman, SL, Rezwan, FI, Simpkin, AJ, Burrows, K, Richardson, TG, Ferreira, D L S, Fraser, A, Harmon, QE, Zhao, SS, Jaddoe, Vincent, Czamara, D, Binder, EB, Magnus, MC, Haberg, SE, Nystad, W, Nohr, EA, Starling, AP, Kechris, KJ, Yang, IV, DeMeo, DL, Litonjua, AA, Baccarelli, A, Oken, E, Holloway, JW, Karmaus, W, Arshad, SH, Dabelea, D, Sorensen, TIA, Laivuori, H, Raikkonen, K, Felix, Janine, London, SJ, Hivert, MF, Gaunt, TR, Lawlor, DA, Relton, CL, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Developmental Psychology Research Group, Helsinki Collegium for Advanced Studies, University of Helsinki, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Pregnancy and Genes, University Management, Department of Medical and Clinical Genetics, Helsinki Institute of Life Science HiLIFE, Faculty of Medicine, Epidemiology, Erasmus MC other, and Pediatrics
Subjects: Adult, pre-eclampsia, hypertension, BIRTH, HYPOMETHYLATION, VASOPRESSIN, BLOOD-PRESSURE, Gestational Age, Epigenesis, Genetic, preeclampsia, Cohort Studies, Hypertension, Pregnancy-Induced/diagnosis, Pregnancy, gestational hypertension, Humans, COHORT, gestational age, METAANALYSIS, ASSOCIATIONS, DNA methylation, epigenetics, NORWEGIAN MOTHER, Infant, Newborn, Pregnancy Outcome, DNA, ALSPAC, Fetal Blood, cardiovascular diseases, 3121 General medicine, internal medicine and other clinical medicine, GENERATION R, FETAL-GROWTH, Female, methylation, DNA-Binding Proteins/genetics, Infant, Premature, Genome-Wide Association Study, DNA Methylation/genetics
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 (R-2=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

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

Author: Czamara, D, Eraslan, G, Page, CM, Laivuori, H, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University
Subjects: Genetiikka, kehitysbiologia, fysiologia - Genetics, developmental biology, physiology
Published: 2019

42. 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
Full Text: View/download PDF

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

Author: Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna 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 Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), 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., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), 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.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), 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. (Jürgen), Willemsen, G.A.H.M. (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., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), 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., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), Binder, E.B. (Elisabeth), Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna 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 Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), 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., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), 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.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), 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. (Jürgen), Willemsen, G.A.H.M. (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., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), 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., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), and Binder, E.B. (Elisabeth)
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
Full Text: View/download PDF

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

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

45. 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

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

Author: Kazmi, N, Sharp, GC, Reese, SE, Vehmeijer, FO, Lahti, J, Page, CM, Zhang, WM, Rifas-Shiman, SL, Rezwan, FI, Simpkin, AJ, Burrows, K, Richardson, TG, Ferreira, D L S, Fraser, A, Harmon, QE, Zhao, SS, Jaddoe, Vincent, Czamara, D, Binder, EB, Magnus, MC, Haberg, SE, Nystad, W, Nohr, EA, Starling, AP, Kechris, KJ, Yang, IV, DeMeo, DL, Litonjua, AA, Baccarelli, A, Oken, E, Holloway, JW, Karmaus, W, Arshad, SH, Dabelea, D, Sorensen, TIA, Laivuori, H, Raikkonen, K, Felix, Janine, London, SJ, Hivert, MF, Gaunt, TR, Lawlor, DA, Relton, CL, Kazmi, N, Sharp, GC, Reese, SE, Vehmeijer, FO, Lahti, J, Page, CM, Zhang, WM, Rifas-Shiman, SL, Rezwan, FI, Simpkin, AJ, Burrows, K, Richardson, TG, Ferreira, D L S, Fraser, A, Harmon, QE, Zhao, SS, Jaddoe, Vincent, Czamara, D, Binder, EB, Magnus, MC, Haberg, SE, Nystad, W, Nohr, EA, Starling, AP, Kechris, KJ, Yang, IV, DeMeo, DL, Litonjua, AA, Baccarelli, A, Oken, E, Holloway, JW, Karmaus, W, Arshad, SH, Dabelea, D, Sorensen, TIA, Laivuori, H, Raikkonen, K, Felix, Janine, London, SJ, Hivert, MF, Gaunt, TR, Lawlor, DA, and Relton, CL
Published: 2019

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

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

48. Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma

Author: Becker, J., May, A., Gerges, C., Anders, M., Veits, L., Weise, K., Czamara, D., Lyros, O., Manner, H., Terheggen, G., Venerito, M., Noder, T., Mayershofer, R., Hofer, J., Karch, H., Ahlbrand, C., Arras, M., Hofer, S., Mangold, E., Heilmann-Heimbach, S., Heinrichs, S., Hess, T., Kiesslich, R., Izbicki, J., Hoelscher, A., Bollschweiler, E., Malfertheiner, P., Lang, H., Moehler, M., Lorenz, D., Müller-Myhsok, B., Ott, K., Schmidt, T., Whiteman, D., Vaughan, T., Noethen, M., Hackelsberger, A., Schumacher, B., Pech, O., Vashist, Y., Vieth, M., Weismueller, J., Neuhaus, H., Roesch, T., Ell, C., Gockel, I., and Schumacher, J.
Subjects: Adult, Male, esophageal adenocarcinoma, Adolescent, Esophageal Neoplasms, Genotype, FOXP1, Adenocarcinoma, BARX1, Polymorphism, Single Nucleotide, Young Adult, Odds Ratio, Humans, Genetic Predisposition to Disease, FOXF1, Alleles, Genetic Association Studies, Cancer Biology, Homeodomain Proteins, Forkhead Transcription Factors, Repressor Proteins, Genetic Loci, genetic association study, Case-Control Studies, Female, Genome-Wide Association Study, Transcription Factors
Abstract: The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P< 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P
Published: 2015

49. Polygenic risk for immuno-metabolic markers and specific depressive symptoms: A multi-sample network analysis study

Author: Kappelmann, N., Czamara, D., Rost, N., Moser, S., Schmoll, V., Trastulla, L., Stochl, J., Lucae, S., CHARGE inflammation working group, Binder, E.B., Khandaker, G.M., and Arloth, J.
Published: 2021
Full Text: View/download PDF

50. FoxO1, A2M, and TGF-β1:three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses

Author: Cattaneo, A. (Annamaria), Cattane, N. (Nadia), Malpighi, C. (Chiara), Czamara, D. (Darina), Suarez, A. (Anna), Mariani, N. (Nicole), Kajantie, E. (Eero), Luoni, A. (Alessia), Eriksson, J. G. (Johan G.), Lahti, J. (Jari), Mondelli, V. (Valeria), Dazzan, P. (Paola), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), Riva, M. A. (Marco A.), Pariante, C. M. (Carmine M.), Cattaneo, A. (Annamaria), Cattane, N. (Nadia), Malpighi, C. (Chiara), Czamara, D. (Darina), Suarez, A. (Anna), Mariani, N. (Nicole), Kajantie, E. (Eero), Luoni, A. (Alessia), Eriksson, J. G. (Johan G.), Lahti, J. (Jari), Mondelli, V. (Valeria), Dazzan, P. (Paola), Räikkönen, K. (Katri), Binder, E. B. (Elisabeth B.), Riva, M. A. (Marco A.), and Pariante, C. M. (Carmine M.)
Abstract: To date, gene-environment (GxE) interaction studies in depression have been limited to hypothesis-based candidate genes, since genome-wide (GWAS)-based GxE interaction studies would require enormous datasets with genetics, environmental, and clinical variables. We used a novel, cross-species and cross-tissues “omics” approach to identify genes predicting depression in response to stress in GxE interactions. We integrated the transcriptome and miRNome profiles from the hippocampus of adult rats exposed to prenatal stress (PNS) with transcriptome data obtained from blood mRNA of adult humans exposed to early life trauma, using a stringent statistical analyses pathway. Network analysis of the integrated gene lists identified the Forkhead box protein O1 (FoxO1), Alpha-2-Macroglobulin (A2M), and Transforming Growth Factor Beta 1 (TGF-β1) as candidates to be tested for GxE interactions, in two GWAS samples of adults either with a range of childhood traumatic experiences (Grady Study Project, Atlanta, USA) or with separation from parents in childhood only (Helsinki Birth Cohort Study, Finland). After correction for multiple testing, a meta-analysis across both samples confirmed six FoxO1 SNPs showing significant GxE interactions with early life emotional stress in predicting depressive symptoms. Moreover, in vitro experiments in a human hippocampal progenitor cell line confirmed a functional role of FoxO1 in stress responsivity. In secondary analyses, A2M and TGF-β1 showed significant GxE interactions with emotional, physical, and sexual abuse in the Grady Study. We therefore provide a successful ‘hypothesis-free’ approach for the identification and prioritization of candidate genes for GxE interaction studies that can be investigated in GWAS datasets.
Published: 2018

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

214 results on '"Czamara, D"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources