المؤلفون: Gruzieva, O, Xu, CJ, Yousefi, P, Relton, C, Merid, SK, Breton, CV, Gao, L, Volk, HE, Feinberg, JI, Ladd-Acosta, C, Bakulski, K, Auffray, C, Lemonnier, N, Plusquin, M, Ghantous, A, Herceg, Z, Nawrot, TS, Pizzi, C, Richiardi, L, Rusconi, F, Vineis, P, Kogevinas, M, Felix, JF, Duijts, L, den Dekker, HT, Jaddoe, VWV, Ruiz, JL, Bustamante, M, Anto, JM, Sunyer, J, Vrijheid, M, Gutzkow, KB, Grazuleviciene, R, Hernandez-Ferrer, C, Annesi-Maesano, I, Lepeule, J, Bousquet, J, Bergstrom, A, Kull, I, Soderhall, C, Kere, J, Gehring, U, Brunekreef, B, Just, AC, Wright, RJ, Peng, C, Gold, DR, Kloog, I, DeMeo, DL, Pershagen, G, Koppelman, GH, London, SJ, Baccarelli, AA, Melen, E

المصدر: Environmental health perspectives. 127(5):57012

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:141116772Test

المؤلفون: Agha G., Mendelson M. M., Ward-Caviness C. K., Joehanes R., Huan T., Gondalia R., Salfati E., Brody J. A., Fiorito G., Bressler J., Chen B. H., Ligthart S., Guarrera S., Colicino E., Just A. C., Wahl S., Gieger C., Vandiver A. R., Tanaka T., Hernandez D. G., Pilling L. C., Singleton A. B., Sacerdote C., Krogh V., Panico S., Tumino R., Li Y., Zhang G., Stewart J. D., Floyd J. S., Wiggins K. L., Rotter J. I., Multhaup M., Bakulski K., Horvath S., Tsao P. S., Absher D. M., Vokonas P., Hirschhorn J., Fallin M. D., Liu C., Bandinelli S., Boerwinkle E., Dehghan A., Schwartz J. D., Psaty B. M., Feinberg A. P., Hou L., Ferrucci L., Sotoodehnia N., Matullo G., Peters A., Fornage M., Assimes T. L., Whitsel E. A., Levy D., Baccarelli A. A.

المساهمون: Agha G., Mendelson M.M., Ward-Caviness C.K., Joehanes R., Huan T., Gondalia R., Salfati E., Brody J.A., Fiorito G., Bressler J., Chen B.H., Ligthart S., Guarrera S., Colicino E., Just A.C., Wahl S., Gieger C., Vandiver A.R., Tanaka T., Hernandez D.G., Pilling L.C., Singleton A.B., Sacerdote C., Krogh V., Panico S., Tumino R., Li Y., Zhang G., Stewart J.D., Floyd J.S., Wiggins K.L., Rotter J.I., Multhaup M., Bakulski K., Horvath S., Tsao P.S., Absher D.M., Vokonas P., Hirschhorn J., Fallin M.D., Liu C., Bandinelli S., Boerwinkle E., Dehghan A., Schwartz J.D., Psaty B.M., Feinberg A.P., Hou L., Ferrucci L., Sotoodehnia N., Matullo G., Peters A., Fornage M., Assimes T.L., Whitsel E.A., Levy D., Baccarelli A.A.

مصطلحات موضوعية: coronary artery disease, coronary heart disease, epigenetic, gene expression regulation, genomics

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31424985; info:eu-repo/semantics/altIdentifier/wos/WOS:000484336700015; volume:140; issue:8; firstpage:645; lastpage:657; numberofpages:13; journal:CIRCULATION; http://hdl.handle.net/2318/1725865Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85071560527; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812683Test/

الإتاحة: https://doi.org/10.1161/CIRCULATIONAHA.118.039357Test
http://hdl.handle.net/2318/1725865Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812683Test/

المؤلفون: Choudhary, P., Monasso, G., Karhunen, V., Ronkainen, J., Mancano, G., Howe, C., Niu, Z., Zeng, X., Guan, W., Dou, J., Feinberg, J., Mordaunt, C., Pesce, G., Baiz, N., Alfano, R., Martens, D., Wang, C., Isaevska, E., Keikkala, E., Mustaniemi, S., Thio, C., Fraszczyk, E., Tobi, E., Starling, A., Cosin-Tomas, M., Urquiza, J., Roeder, S., Hoang, T., Page, C., Jima, D., House, J., Maguire, R., Ott, R., Pawlow, X., Sirignano, L., Zillich, L., Malmberg, A., Rauschert, S., Melton, P., Gong, T., Karlsson, R., Fore, R., Perng, W., Laubach, Z., Czamara, D., Sharp, G., Breton, C., Schisterman, E., Yeung, E., Mumford, S., Fallin, M., Lasalle, J., Schmidt, R., Bakulski, K., Annesi-Maesano, I., Heude, B., Nawrot, T., Plusquin, M., Ghantous, A., Herceg, Z., Nistico, L., Vafeiadi, M., Kogevinas, M., Vaeaeraesmaeki, M., Kajantie, E., Snieder, H., Corpeleijn, E., Steegers-Theunissen, R., Yang, I., Dabelea, D., Fossati, S., Zenclussen, A., Herberth, G., Magnus, M., Haberg, S., London, S., Munthe-Kaas, M., Murphy, S., Hoyo, C., Ziegler, A., Hummel, S., Witt, S., Streit, F., Frank, J., Raeikkoenen, K., Lahti, J., Huang, R., Almqvist, C., Hivert, M., Jaddoe, V., Jaervelin, M., Kantomaa, M., Felix, J., Sebert, S.

المصدر: MOLECULAR PSYCHIATRY

الوصف: 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.

العلاقة: http://hdl.handle.net/21.11116/0000-000E-3F64-CTest

الإتاحة: https://doi.org/10.1038/s41380-023-02331-5Test
http://hdl.handle.net/21.11116/0000-000E-3F64-CTest

المؤلفون: Kadalayil, L., Alam, M., White, C., Ghantous, A., Walton, E., Gruzieva, O., Merid, S., Kumar, A., Roy, R., Solomon, O., Huen, K., Eskenazi, B., Rzehak, P., Grote, V., Langhendries, J., Verduci, E., Ferre, N., Gruszfeld, D., Gao, L., Guan, W., Zeng, X., Schisterman, E., Dou, J., Bakulski, K., Feinberg, J., Soomro, M., Pesce, G., Baiz, N., Isaevska, E., Plusquin, M., Vafeiadi, M., Roumeliotaki, T., Langie, S., Standaert, A., Allard, C., Perron, P., Bouchard, L., van Meel, E., Felix, J., Jaddoe, V., Yousefi, P., Ramlau-Hansen, C., Relton, C., Tobi, E., Starling, A., Yang, I., Llambrich, M., Santorelli, G., Lepeule, J., Salas, L., Bustamante, M., Ewart, S., Zhang, H., Karmaus, W., Roeder, S., Zenclussen, A., Jin, J., Nystad, W., Page, C., Magnus, M., Jima, D., Hoyo, C., Maguire, R., Kvist, T., Czamara, D., Raikkonen, K., Gong, T., Ullemar, V., Rifas-Shiman, S., Oken, E., Almqvist, C., Karlsson, R., Lahti, J., Murphy, S., Haberg, S., London, S., Herberth, G., Arshad, H., Sunyer, J., Grazuleviciene, R., Dabelea, D., Steegers-Theunissen, R., Nohr, E., Sorensen, T., Duijts, L., Hivert, M., Nelen, V., Popovic, M., Kogevinas, M., Nawrot, T., Herceg, Z., Annesi-Maesano, I., Fallin, M., Yeung, E., Breton, C., Koletzko, B., Holland, N., Wiemels, J., Melen, E., Sharp, G., Silver, M., Rezwan I, F., Holloway, J.

المصدر: CLINICAL EPIGENETICS

الوصف: Background Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. Results We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (>= 50 degrees N), lower (< 50 degrees 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 degrees N). Conclusions In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations ...

العلاقة: http://hdl.handle.net/21.11116/0000-000D-DEC6-ATest

الإتاحة: https://doi.org/10.1186/s13148-023-01542-5Test
http://hdl.handle.net/21.11116/0000-000D-DEC6-ATest

المؤلفون: Ruehlmann, A., Sammallahti, S., Hidalgo, A., Bakulski, K., Binder, E., Campbell, M., Caramaschi, D., Cecil, C., Colicino, E., Cruceanu, C., Czamara, D., Dieckmann, L., Dou, J., Felix, J., Frank, J., Haberg, S., Herberth, G., Hoang, T., Houtepen, L., Huls, A., Koen, N., London, S., Magnus, M., Mancano, G., Mulder, R., Page, C., Raikkonen, K., Roeder, S., Schmidt, R., Send, T., Sharp, G., Stein, D., Streit, F., Tuhkanen, J., Witt, S., Zar, H., Zenclussen, A., Zhang, Y., Zillich, L., Wright, R., Lahti, J., Brunst, K.

المصدر: MOLECULAR PSYCHIATRY

الوصف: Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (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.

العلاقة: http://hdl.handle.net/21.11116/0000-000D-0743-0Test

الإتاحة: https://doi.org/10.1038/s41380-023-02010-5Test
http://hdl.handle.net/21.11116/0000-000D-0743-0Test

المؤلفون: Kupers L. K., Monnereau C., Sharp G. C., Yousefi P., Salas L. A., Ghantous A., Page C. M., Reese S. E., Wilcox A. J., Czamara D., Starling A. P., Novoloaca A., Lent S., Roy R., Hoyo C., Breton C. V., Allard C., Just A. C., Bakulski K. M., Holloway J. W., Everson T. M., Xu C. -J., Huang R. -C., van der Plaat D. A., Wielscher M., Merid S. K., Ullemar V., Rezwan F. I., Lahti J., van Dongen J., Langie S. A. S., Richardson T. G., Magnus M. C., Nohr E. A., Xu Z., Duijts L., Zhao S., Zhang W., Plusquin M., DeMeo D. L., Solomon O., Heimovaara J. H., Jima D. D., Gao L., Bustamante M., Perron P., Wright R. O., Hertz-Picciotto I., Zhang H., Karagas M. R., Gehring U., Marsit C. J., Beilin L. J., Vonk J. M., Jarvelin M. -R., Bergstrom A., Ortqvist A. K., Ewart S., Villa P. M., Moore S. E., Willemsen G., Standaert A. R. L., Haberg S. E., Sorensen T. I. A., Taylor J. A., Raikkonen K., Yang I. V., Kechris K., Nawrot T. S., Silver M. J., Gong Y. Y., Richiardi L., Kogevinas M., Litonjua A. A., Eskenazi B., Huen K., Mbarek H., Maguire R. L., Dwyer T., Vrijheid M., Bouchard L., Baccarelli A. A., Croen L. A., Karmaus W., Anderson D., de Vries M., Sebert S., Kere J., Karlsson R., Arshad S. H., Hamalainen E., Routledge M. N., Boomsma D. I., Feinberg A. P., Newschaffer C. J., Govarts E., Moisse M., Fallin M. D., Melen E., Prentice A. M., Kajantie E., Almqvist C., Oken E., Dabelea D., Boezen H. M., Melton P. E., Wright R. J., Koppelman G. H., Trevisi L., Hivert M. -F., Sunyer J., Munthe-Kaas M. C., Murphy S. K., Corpeleijn E., Wiemels J., Holland N., Herceg Z., Binder E. B., Davey Smith G., Jaddoe V. W. V., Lie R. T., Nystad W., London S. J., Lawlor D. A., Relton C. L., Snieder H., Felix J. F.

المساهمون: Kupers L.K., Monnereau C., Sharp G.C., Yousefi P., Salas L.A., Ghantous A., Page C.M., Reese S.E., Wilcox A.J., Czamara D., Starling A.P., Novoloaca A., Lent S., Roy R., Hoyo C., Breton C.V., Allard C., Just A.C., Bakulski K.M., Holloway J.W., Everson T.M., Xu C.-J., Huang R.-C., van der Plaat D.A., Wielscher M., Merid S.K., Ullemar V., Rezwan F.I., Lahti J., van Dongen J., Langie S.A.S., Richardson T.G., Magnus M.C., Nohr E.A., Xu Z., Duijts L., Zhao S., Zhang W., Plusquin M., DeMeo D.L., Solomon O., Heimovaara J.H., Jima D.D., Gao L., Bustamante M., Perron P., Wright R.O., Hertz-Picciotto I., Zhang H., Karagas M.R., Gehring U., Marsit C.J., Beilin L.J., Vonk J.M., Jarvelin M.-R., Bergstrom A., Ortqvist A.K., Ewart S., Villa P.M., Moore S.E., Willemsen G., Standaert A.R.L., Haberg S.E., Sorensen T.I.A., Taylor J.A., Raikkonen K., Yang I.V., Kechris K., Nawrot T.S., Silver M.J., Gong Y.Y., Richiardi L., Kogevinas M., Litonjua A.A., Eskenazi B., Huen K., Mbarek H., Maguire R.L., Dwyer T., Vrijheid M., Bouchard L., Baccarelli A.A., Croen L.A., Karmaus W., Anderson D., de Vries M., Sebert S., Kere J., Karlsson R., Arshad S.H., Hamalainen E., Routledge M.N., Boomsma D.I., Feinberg A.P., Newschaffer C.J., Govarts E., Moisse M., Fallin M.D., Melen E., Prentice A.M.

مصطلحات موضوعية: Adolescent, Adult, Birth Weight, Body Mass Index, Child, CpG Island, DNA, DNA Methylation, Female, Fetal Development, Fetu, Folic Acid, Genome-Wide Association Study, Human, Infant, Newborn, Male, Pregnancy, Prenatal Exposure Delayed Effect, Smoking, Epigenesis, Genetic, Genome

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31015461; info:eu-repo/semantics/altIdentifier/wos/WOS:000465201900010; volume:10; issue:1; firstpage:1893; lastpage:1903; numberofpages:11; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2318/1716092Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85064924412; http://www.nature.com/ncomms/index.htmlTest

الإتاحة: https://doi.org/10.1038/s41467-019-09671-3Test
http://hdl.handle.net/2318/1716092Test
http://www.nature.com/ncomms/index.htmlTest

المؤلفون: 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.)

مصطلحات موضوعية: DNA methylation, Epidemiology, Epigenetics, Paediatric research

الوصف: 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.

وصف الملف: application/pdf

الإتاحة: http://urn.fi/urn:nbn:fi-fe2020042822771Test

المؤلفون: Bakulski, K. M., Dou, J., Lin, N., London, S. J., Colacino, J. A.

المساهمون: U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences, U.S. Department of Health & Human Services | NIH | National Institute on Aging

المصدر: Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Smoking impacts DNA methylation genome-wide in blood of newborns from maternal smoking during pregnancy and adults from personal smoking. We compared smoking-related DNA methylation in lung adenocarcinoma (61 never smokers, 91 current smokers, and 238 former smokers) quantified with the Illumina450k BeadArray in The Cancer Genome Atlas with published large consortium meta-analyses of newborn and adult blood. We assessed whether CpG sites related to smoking in blood from newborns and adults were enriched in the lung adenocarcinoma methylation signal. Testing CpGs differentially methylated by smoke exposure, we identified 296 in lung adenocarcinoma meeting a P < 10 −4 cutoff, while previous meta-analyses identified 3,042 in newborn blood, and 8,898 in adult blood meeting the same P < 10 −4 cutoff. Lung signals were highly enriched for those seen in newborn (24 overlapping CpGs, P enrichment = 1.2 × 10 −18 ) and adult blood (66 overlapping CpGs, P enrichment = 1.2 × 10 −48 ). The 105 genes annotated to CpGs differentially methylated in lung tumors, but not blood, were enriched for RNA processing ontologies. Some epigenetic alterations associated with cigarette smoke exposure are tissue specific, but others are common across tissues. These findings support the value of blood-based methylation biomarkers for assessing exposure effects in target tissues.

الإتاحة: https://doi.org/10.1038/s41598-019-40963-2Test
https://www.nature.com/articles/s41598-019-40963-2.pdfTest
https://www.nature.com/articles/s41598-019-40963-2Test

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

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pissn/0300-5771; info:eu-repo/semantics/altIdentifier/eissn/1464-3685

الإتاحة: http://urn.fi/urn:nbn:fi-fe201804136540Test

المؤلفون: Ligthart S., Marzi C., Aslibekyan S., Mendelson M. M., Conneely K. N., Tanaka T., Colicino E., Waite L. L., Joehanes R., Guan W., Brody J. A., Elks C., Marioni R., Jhun M. A., Agha G., Bressler J., Ward-Caviness C. K., Chen B. H., Huan T., Bakulski K., Salfati E. L., Fiorito G., Wahl S., Schramm K., Sha J., Hernandez D. G., Just A. C., Smith J. A., Sotoodehnia N., Pilling L. C., Pankow J. S., Tsao P. S., Liu C., Zhao W., Guarrera S., Michopoulos V. J., Smith A. K., Peters M. J., Melzer D., Vokonas P., Fornage M., Prokisch H., Bis J. C., Chu A. Y., Herder C., Grallert H., Yao C., Shah S., McRae A. F., Lin H., Horvath S., Fallin D., Hofman A., Wareham N. J., Wiggins K. L., Feinberg A. P., Starr J. M., Visscher P. M., Murabito J. M., Kardia S. L. R., Absher D. M., Binder E. B., Singleton A. B., Bandinelli S., Peters A., Waldenberger M., Matullo G., Schwartz J. D., Demerath E. W., Uitterlinden A. G., Meurs J. B. J., Franco O. H., Chen Y. -D. I., Levy D., Turner S. T., Deary I. J., Ressler K. J., Dupuis J., Ferrucci L., Ong K. K., Assimes T. L., Boerwinkle E., Koenig W., Arnett D. K., Baccarelli A. A., Benjamin E. J., Dehghan A.

المساهمون: Ligthart, S., Marzi, C., Aslibekyan, S., Mendelson, M. M., Conneely, K. N., Tanaka, T., Colicino, E., Waite, L. L., Joehanes, R., Guan, W., Brody, J. A., Elks, C., Marioni, R., Jhun, M. A., Agha, G., Bressler, J., Ward-Caviness, C. K., Chen, B. H., Huan, T., Bakulski, K., Salfati, E. L., Fiorito, G., Wahl, S., Schramm, K., Sha, J., Hernandez, D. G., Just, A. C., Smith, J. A., Sotoodehnia, N., Pilling, L. C., Pankow, J. S., Tsao, P. S., Liu, C., Zhao, W., Guarrera, S., Michopoulos, V. J., Smith, A. K., Peters, M. J., Melzer, D., Vokonas, P., Fornage, M., Prokisch, H., Bis, J. C., Chu, A. Y., Herder, C., Grallert, H., Yao, C., Shah, S., Mcrae, A. F., Lin, H., Horvath, S., Fallin, D., Hofman, A., Wareham, N. J., Wiggins, K. L., Feinberg, A. P., Starr, J. M., Visscher, P. M., Murabito, J. M., Kardia, S. L. R., Absher, D. M., Binder, E. B., Singleton, A. B., Bandinelli, S., Peters, A., Waldenberger, M., Matullo, G., Schwartz, J. D., Demerath, E. W., Uitterlinden, A. G., Meurs, J. B. J., Franco, O. H., Chen, Y. -D. I., Levy, D., Turner, S. T., Deary, I. J., Ressler, K. J., Dupuis, J., Ferrucci, L., Ong, K. K., Assimes, T. L., Boerwinkle, E., Koenig, W., Arnett, D. K., Baccarelli, A. A., Benjamin, E. J., Dehghan, A.

مصطلحات موضوعية: Body mass index, C-reactive protein, Coronary heart disease, Diabete, DNA methylation, Epigenome-wide association study, Inflammation

الوصف: Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10-7) in the discovery panel of European ancestry and replicated (P < 2.29 × 10-4) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10-5), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10-3), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10-5). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants. Conclusion: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000390199000001; volume:17; issue:1; journal:GENOME BIOLOGY; http://hdl.handle.net/11388/245439Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85003550816

الإتاحة: https://doi.org/10.1186/s13059-016-1119-5Test
http://hdl.handle.net/11388/245439Test