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145 results on '"van der Vlies, Pieter"'

2. Shared DNA methylation signatures in childhood allergy: The MeDALL study

Author

Xu, Cheng-Jian, Gruzieva, Olena, Qi, Cancan, Esplugues, Ana, Gehring, Ulrike, Bergström, Anna, Mason, Dan, Chatzi, Leda, Porta, Daniela, Lodrup Carlsen, Karin C., Baïz, Nour, Madore, Anne-Marie, Alenius, Harri, van Rijkom, Bianca, Jankipersadsing, Soesma A., van der Vlies, Pieter, Kull, Inger, van Hage, Marianne, Bustamante, Mariona, Lertxundi, Aitana, Torrent, Matias, Santorelli, Gillian, Fantini, Maria Pia, Hovland, Vegard, Pesce, Giancarlo, Fyhrquist, Nanna, Laatikainen, Tiina, Nawijn, Martijn C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Bousquet, Jean, Anto, Josep M., Laprise, Catherine, Haahtela, Tari, Annesi-Maesano, Isabella, Carlsen, Kai-Håkon, Gori, Davide, Kogevinas, Manolis, Wright, John, Söderhäll, Cilla, Vonk, Judith M., Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H.

Published
2021
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3. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Neelon, Sara E Benjamin, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, and Nystad, Wenche

Subjects
Genetics, Pediatric, Human Genome, Tobacco, Tobacco Smoke and Health, Prevention, Aetiology, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Respiratory, Reproductive health and childbirth, Good Health and Well Being, Asthma, Child, Child, Preschool, Chromosome Mapping, Cleft Lip, Cleft Palate, DNA Methylation, Epigenesis, Genetic, Female, Genetic Association Studies, Humans, Infant, Infant, Newborn, Pregnancy, Smoking, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Published
2016

4. Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.

Author

Farlow, Janice L, Lin, Hai, Sauerbeck, Laura, Lai, Dongbing, Koller, Daniel L, Pugh, Elizabeth, Hetrick, Kurt, Ling, Hua, Kleinloog, Rachel, van der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A, Verweij, Bon H, Regli, Luca, Rinkel, Gabriel JE, Ruigrok, Ynte M, Doheny, Kimberly, Liu, Yunlong, Broderick, Joseph, Foroud, Tatiana, and FIA Study Investigators

Subjects
FIA Study Investigators, Humans, Intracranial Aneurysm, Genetic Predisposition to Disease, Membrane Proteins, Cohort Studies, Chromosome Mapping, Pedigree, Sequence Analysis, DNA, Computational Biology, Base Sequence, Phenotype, Molecular Sequence Data, Genetic Variation, Exome, Sequence Analysis, DNA, General Science & Technology
Abstract

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

Published
2015

5. DNA methylation in childhood asthma: an epigenome-wide meta-analysis

Author

Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A, Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J, Aguirre-Gamboa, Raul, de Jongste, Johan C, Smit, Henriette A, Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R C, Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, van der Vlies, Pieter, van Diemen, Cleo C, Li, Yang, Wijmenga, Cisca, Netea, Mihai G, Moffatt, Miriam F, Cookson, William O C M, Anto, Josep M, Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Håkon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manolis, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H

Published
2018
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6. Genetic and epigenetic regulation of YKL-40 in childhood

Author

Guerra, Stefano, Melén, Erik, Sunyer, Jordi, Xu, Cheng-Jian, Lavi, Iris, Benet, Marta, Bustamante, Mariona, Carsin, Anne-Elie, Dobaño, Carlota, Guxens, Mònica, Tischer, Christina, Vrijheid, Martine, Kull, Inger, Bergström, Anna, Kumar, Ashish, Söderhäll, Cilla, Gehring, Ulrike, Dijkstra, Dorieke J., van der Vlies, Pieter, Wickman, Magnus, Bousquet, Jean, Postma, Dirkje S., Anto, Josep M., and Koppelman, Gerard H.

Published
2018
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8. Data from A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

Author

Workel, Hagma H., primary, Lubbers, Joyce M., primary, Arnold, Roland, primary, Prins, Thalina M., primary, van der Vlies, Pieter, primary, de Lange, Kim, primary, Bosse, Tjalling, primary, van Gool, Inge C., primary, Eggink, Florine A., primary, Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, van der Slikke, Elisabeth C., primary, Creutzberg, Carien L., primary, Kol, Arjan, primary, Plat, Annechien, primary, Glaire, Mark, primary, Church, David N., primary, Nijman, Hans W., primary, and de Bruyn, Marco, primary

Published
2023
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9. Supplementary Table 7 from A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

Author

Workel, Hagma H., primary, Lubbers, Joyce M., primary, Arnold, Roland, primary, Prins, Thalina M., primary, van der Vlies, Pieter, primary, de Lange, Kim, primary, Bosse, Tjalling, primary, van Gool, Inge C., primary, Eggink, Florine A., primary, Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, van der Slikke, Elisabeth C., primary, Creutzberg, Carien L., primary, Kol, Arjan, primary, Plat, Annechien, primary, Glaire, Mark, primary, Church, David N., primary, Nijman, Hans W., primary, and de Bruyn, Marco, primary

Published
2023
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10. Supplementary Tables 1-6, 8 from A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

Author

Workel, Hagma H., primary, Lubbers, Joyce M., primary, Arnold, Roland, primary, Prins, Thalina M., primary, van der Vlies, Pieter, primary, de Lange, Kim, primary, Bosse, Tjalling, primary, van Gool, Inge C., primary, Eggink, Florine A., primary, Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, van der Slikke, Elisabeth C., primary, Creutzberg, Carien L., primary, Kol, Arjan, primary, Plat, Annechien, primary, Glaire, Mark, primary, Church, David N., primary, Nijman, Hans W., primary, and de Bruyn, Marco, primary

Published
2023
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11. Supplementary Figures from A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

Author

Workel, Hagma H., primary, Lubbers, Joyce M., primary, Arnold, Roland, primary, Prins, Thalina M., primary, van der Vlies, Pieter, primary, de Lange, Kim, primary, Bosse, Tjalling, primary, van Gool, Inge C., primary, Eggink, Florine A., primary, Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, van der Slikke, Elisabeth C., primary, Creutzberg, Carien L., primary, Kol, Arjan, primary, Plat, Annechien, primary, Glaire, Mark, primary, Church, David N., primary, Nijman, Hans W., primary, and de Bruyn, Marco, primary

Published
2023
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19. RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture

Author

Kleinloog, Rachel, Verweij, Bon H., van der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., de Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, van der Zwan, Albert, Berkelbach van der Sprenkel, Jan W., Han, K. Sen, Gosselaar, Peter, van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J.E., Veldink, Jan H., and Ruigrok, Ynte M.

Published
2016
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20. Shared DNA methylation signatures in childhood allergy: The MeDALL study

Author

Medicina preventiva y salud pública, Prebentzio medikuntza eta osasun publikoa, Xu, Cheng-Jian, Gruzieva, Olena, Qi, Cancan, Esplugues, Ana, Gehring, Ulrike, Bergström, Anna, Mason, Dan, Chatzi, Leda, Porta, Daniela, Lodrup Carlsen, Karin C., Baïz, Nour, Madore, Anne-Marie, Alenius, Harri, Van Rijkom, Bianca, Jankipersadsing, Soesma A., Van der Vlies, Pieter, Kull, Inger, Van Hage, Marianne, Bustamante, Mariona, Lertxundi Manterola, Aitana, Torrent, Matias, Santore, Gillian, Fantini, Maria Pia, Hovland, Vegard, Pesce, Giancarlo, BIOS Consortium, Fyhrquist, Nanna, Laatikainen, Tiina, Nawijn, Martijn C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Bousquet, Jean, Anto, Josep M., Laprise, Catherine, Haahtela, Tari, Annesi-Maesano, Isabella, Carlsen, Kai-Håkon, Gori, Davide, Kogevinas, Manolis, Wright, John, Söderhäll, Cilla, Vonk, Judith M., Sunyer, Jordi, Melén, Erik, Koppelman, Gerard H., Medicina preventiva y salud pública, Prebentzio medikuntza eta osasun publikoa, Xu, Cheng-Jian, Gruzieva, Olena, Qi, Cancan, Esplugues, Ana, Gehring, Ulrike, Bergström, Anna, Mason, Dan, Chatzi, Leda, Porta, Daniela, Lodrup Carlsen, Karin C., Baïz, Nour, Madore, Anne-Marie, Alenius, Harri, Van Rijkom, Bianca, Jankipersadsing, Soesma A., Van der Vlies, Pieter, Kull, Inger, Van Hage, Marianne, Bustamante, Mariona, Lertxundi Manterola, Aitana, Torrent, Matias, Santore, Gillian, Fantini, Maria Pia, Hovland, Vegard, Pesce, Giancarlo, BIOS Consortium, Fyhrquist, Nanna, Laatikainen, Tiina, Nawijn, Martijn C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Bousquet, Jean, Anto, Josep M., Laprise, Catherine, Haahtela, Tari, Annesi-Maesano, Isabella, Carlsen, Kai-Håkon, Gori, Davide, Kogevinas, Manolis, Wright, John, Söderhäll, Cilla, Vonk, Judith M., Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H.

Abstract

BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylationprofilesassociated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses. RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium. CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.

Published
2021

21. Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD+ in medium-chain acyl-CoA dehydrogenase knockout mice

Author

LS Pathobiologie, dPB RMSC, Martines, Anne-Claire M F, Gerding, Albert, Stolle, Sarah, Vieira-Lara, Marcel A, Wolters, Justina C, Jurdzinski, Angelika, Bongiovanni, Laura, de Bruin, Alain, van der Vlies, Pieter, van der Vries, Gerben, Bloks, Vincent W, Derks, Terry G J, Reijngoud, Dirk-Jan, Bakker, Barbara M, LS Pathobiologie, dPB RMSC, Martines, Anne-Claire M F, Gerding, Albert, Stolle, Sarah, Vieira-Lara, Marcel A, Wolters, Justina C, Jurdzinski, Angelika, Bongiovanni, Laura, de Bruin, Alain, van der Vlies, Pieter, van der Vries, Gerben, Bloks, Vincent W, Derks, Terry G J, Reijngoud, Dirk-Jan, and Bakker, Barbara M

Published
2019

22. Genetic regulation ofmethylation and IL1RL1-a protein levels in asthma

Author

Dijk, F Nicole, Xu, Chengjian, Melén, Erik, Carsin, Anne-Elie, Kumar, Asish, Nolte, Ilja M, Gruzieva, Olena, Pershagen, Goran, Grotenboer, Neomi S, Savenije, Olga E M, Antó, Josep Maria, Lavi, Iris, Dobaño, Carlota, Bousquet, Jean, van der Vlies, Pieter, van der Valk, Ralf J P, de Jongste, Johan C, Nawijn, Martijn C, Guerra, Stefano, Postma, Dirkje S, Koppelman, Gerard H, Life Course Epidemiology (LCE), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
VARIANT FORM, CYTOKINE, AIRWAY INFLAMMATION, PROMOTER, HUMAN ST2 GENE, Journal Article, IL-33, GENOME-WIDE ASSOCIATION, RECEPTOR-LIKE 1, POLYMORPHISMS, METAANALYSIS, respiratory tract diseases
Abstract

Interleukin-1 receptor-like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation ofIL1RL1protein expression has not been established. We assessed the association betweenIL1RL1single nucleotide polymorphisms (SNPs),IL1RL1methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations ofIL1RL1SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNAIL1RL1methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association ofIL1RL1CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101).IL1RL1asthma-risk SNPs strongly associated withIL1RL1methylation (rs1420101; p=3.7×10-16) and serum IL1RL1-a levels (p=2.8×10-56).IL1RL1methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associatedIL1RL1SNPs strongly regulateIL1RL1methylation and serum IL1RL1-a levels, yet neither theseIL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.

Published
2018

23. A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

Author

Workel, Hagma H., primary, Lubbers, Joyce M., additional, Arnold, Roland, additional, Prins, Thalina M., additional, van der Vlies, Pieter, additional, de Lange, Kim, additional, Bosse, Tjalling, additional, van Gool, Inge C., additional, Eggink, Florine A., additional, Wouters, Maartje C.A., additional, Komdeur, Fenne L., additional, van der Slikke, Elisabeth C., additional, Creutzberg, Carien L., additional, Kol, Arjan, additional, Plat, Annechien, additional, Glaire, Mark, additional, Church, David N., additional, Nijman, Hans W., additional, and de Bruyn, Marco, additional

Published
2019
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24. DNA methylation in childhood asthma : an epigenome-wide meta-analysis

Author

Xu, Cheng Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C.Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Brunekreef, Bert, the BIOS Consortium, Xu, Cheng Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C.Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Brunekreef, Bert, and the BIOS Consortium

Published
2018

25. DNA methylation in childhood asthma: an epigenome-wide meta-analysis

Author

One Health Chemisch, dIRAS RA-2, Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A, Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J, Aguirre-Gamboa, Raul, de Jongste, Johan C, Smit, Henriette A, Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R C, Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, the BIOS Consortium, van der Vlies, Pieter, van Diemen, Cleo C, Li, Yang, Wijmenga, Cisca, Netea, Mihai G, Moffatt, Miriam F, Cookson, William O C M, Anto, Josep M, Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Hakon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manolis, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, Koppelman, Gerard H, One Health Chemisch, dIRAS RA-2, Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A, Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J, Aguirre-Gamboa, Raul, de Jongste, Johan C, Smit, Henriette A, Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R C, Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, the BIOS Consortium, van der Vlies, Pieter, van Diemen, Cleo C, Li, Yang, Wijmenga, Cisca, Netea, Mihai G, Moffatt, Miriam F, Cookson, William O C M, Anto, Josep M, Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Hakon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manolis, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H

Published
2018

26. Genetic and epigenetic regulation of YKL-40 in childhood

Author

One Health Chemisch, dIRAS RA-2, Guerra, Stefano, Melén, Erik, Sunyer, Jordi, Xu, Cheng-Jian, Lavi, Iris, Benet, Marta, Bustamante, Mariona, Carsin, Anne-Elie, Dobaño, Carlota, Guxens, Mònica, Tischer, Christina, Vrijheid, Martine, Kull, Inger, Bergström, Anna, Kumar, Ashish, Söderhäll, Cilla, Gehring, Ulrike, Dijkstra, Dorieke J, van der Vlies, Pieter, Wickman, Magnus, Bousquet, Jean, Postma, Dirkje S, Anto, Josep M, Koppelman, Gerard H, One Health Chemisch, dIRAS RA-2, Guerra, Stefano, Melén, Erik, Sunyer, Jordi, Xu, Cheng-Jian, Lavi, Iris, Benet, Marta, Bustamante, Mariona, Carsin, Anne-Elie, Dobaño, Carlota, Guxens, Mònica, Tischer, Christina, Vrijheid, Martine, Kull, Inger, Bergström, Anna, Kumar, Ashish, Söderhäll, Cilla, Gehring, Ulrike, Dijkstra, Dorieke J, van der Vlies, Pieter, Wickman, Magnus, Bousquet, Jean, Postma, Dirkje S, Anto, Josep M, and Koppelman, Gerard H

Published
2018

27. DNA methylation in childhood asthma: an epigenome-wide meta-analysis

Author

Public Health Epidemiologie, Circulatory Health, Child Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Infectieziekten, Epi Infectieziekten Team 3, Xu, Cheng Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C.Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Brunekreef, Bert, the BIOS Consortium, Public Health Epidemiologie, Circulatory Health, Child Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Infectieziekten, Epi Infectieziekten Team 3, Xu, Cheng Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C.Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Brunekreef, Bert, and the BIOS Consortium

Published
2018

28. The emerging landscape of dynamic DNA methylation in early childhood

Author

Xu, Cheng-Jian, Bonder, Marc Jan, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gehring, Ulrike, Jankipersadsing, Soesma A, Van Der Vlies, Pieter, van Diemen, Cleo C, van Rijkom, Bianca, Just, Jocelyne, Kull, Inger, Kere, Juha, Antó, Josep Maria, Bousquet, Jean, Zhernakova, Alexandra, Wijmenga, Cisca, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, Li, Yang, Postma, Dirkje S, Koppelman, Gerard H, LS IRAS EEPI ME (Milieu epidemiologie), dIRAS RA-2, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Research Programs Unit, Juha Kere / Principal Investigator, LS IRAS EEPI ME (Milieu epidemiologie), dIRAS RA-2, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Epigenomics, 0301 basic medicine, Aging, Methylation quatitative trait loci, ADN, DISEASE, Methylation quantitative trait loci, Epigenesis, Genetic, Child Development, Pregnancy, Non-U.S. Gov't, Child, POPULATION, Maternal smoking, Genetics, DNA methylation, NEWBORNS, Research Support, Non-U.S. Gov't, Smoking, 1184 Genetics, developmental biology, physiology, Environmental exposure, Methylation, 3. Good health, D-ASPARTATE, Maternal Exposure, Child, Preschool, Prenatal Exposure Delayed Effects, Female, Metilació, PROJECT, Research Article, Infància, Biotechnology, Quantitative Trait Loci, Genomics, Quantitative trait locus, Biology, Research Support, 03 medical and health sciences, AGE, Genetic, MICROARRAY, Journal Article, Humans, Genetic Predisposition to Disease, COHORT, Epigenetics, Preschool, Gene, METAANALYSIS, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Infant, Newborn, Genetic Variation, Infant, DNA, DNA Methylation, Newborn, Childhood, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, ASTHMA, CpG Islands, 3111 Biomedicine, Epigenesis, Genome-Wide Association Study
Abstract

Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. Results: By analysing 538 paired DNA blood samples from children at birth and at 4–5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p

Published
2017
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29. Differences in gene expression related to the results of obesity treatment, peak oxygen uptake and fatty acid metabolism measured in a cardiopulmonary exercise test

Author

Gruchała-Niedoszytko, Marta, primary, van der Vlies, Pieter, additional, Niedoszytko, Piotr, additional, Sanjabi, Bahram, additional, Niedoszytko, Marek, additional, Kaczkan, Małgorzata, additional, Pieszko, Magdalena, additional, Gierat-Haponiuk, Katarzyna, additional, Śliwińska, Aleksandra, additional, Szalewska, Dominika, additional, and Małgorzewicz, Sylwia, additional

Published
2018
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30. Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma

Author

Dijk, F. Nicole, primary, Xu, Chengjian, additional, Melén, Erik, additional, Carsin, Anne-Elie, additional, Kumar, Asish, additional, Nolte, Ilja M., additional, Gruzieva, Olena, additional, Pershagen, Goran, additional, Grotenboer, Neomi S., additional, Savenije, Olga E.M., additional, Antó, Josep Maria, additional, Lavi, Iris, additional, Dobaño, Carlota, additional, Bousquet, Jean, additional, van der Vlies, Pieter, additional, van der Valk, Ralf J.P., additional, de Jongste, Johan C., additional, Nawijn, Martijn C., additional, Guerra, Stefano, additional, Postma, Dirkje S., additional, and Koppelman, Gerard H., additional

Published
2018
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31. The emerging landscape of dynamic DNA methylation in early childhood

Author

LS IRAS EEPI ME (Milieu epidemiologie), dIRAS RA-2, Xu, Cheng-Jian, Bonder, Marc Jan, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gehring, Ulrike, Jankipersadsing, Soesma A, Van Der Vlies, Pieter, van Diemen, Cleo C, van Rijkom, Bianca, Just, Jocelyne, Kull, Inger, Kere, Juha, Antó, Josep Maria, Bousquet, Jean, Zhernakova, Alexandra, Wijmenga, Cisca, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, Li, Yang, Postma, Dirkje S, Koppelman, Gerard H, LS IRAS EEPI ME (Milieu epidemiologie), dIRAS RA-2, Xu, Cheng-Jian, Bonder, Marc Jan, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gehring, Ulrike, Jankipersadsing, Soesma A, Van Der Vlies, Pieter, van Diemen, Cleo C, van Rijkom, Bianca, Just, Jocelyne, Kull, Inger, Kere, Juha, Antó, Josep Maria, Bousquet, Jean, Zhernakova, Alexandra, Wijmenga, Cisca, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, Li, Yang, Postma, Dirkje S, and Koppelman, Gerard H

Published
2017

32. Running-wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post-transcriptional mechanism

Author

Stolle, Sarah, primary, Ciapaite, Jolita, additional, Reijne, Aaffien C., additional, Talarovicova, Alzbeta, additional, Wolters, Justina C., additional, Aguirre-Gamboa, Raúl, additional, van der Vlies, Pieter, additional, de Lange, Kim, additional, Neerincx, Pieter B., additional, van der Vries, Gerben, additional, Deelen, Patrick, additional, Swertz, Morris A., additional, Li, Yang, additional, Bischoff, Rainer, additional, Permentier, Hjalmar P., additional, Horvatovitch, Peter L., additional, Groen, Albert K., additional, van Dijk, Gertjan, additional, Reijngoud, Dirk-Jan, additional, and Bakker, Barbara M., additional

Published
2017
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34. RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture

Author

Celbiologie, Sub Cell Biology, Kleinloog, Rachel, Verweij, Bon H., Van Der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., De Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, Van Der Zwan, Albert, Van Der Sprenkel, Jan W. Berkelbach, Han, K. Sen, Gosselaar, Peter, Van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Celbiologie, Sub Cell Biology, Kleinloog, Rachel, Verweij, Bon H., Van Der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., De Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, Van Der Zwan, Albert, Van Der Sprenkel, Jan W. Berkelbach, Han, K. Sen, Gosselaar, Peter, Van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J.E., Veldink, Jan H., and Ruigrok, Ynte M.

Published
2016

35. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, London, Stephanie J, dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, and London, Stephanie J

Published
2016

36. RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture

Author

Cell Biology, Neurobiology and Biophysics, Sub Cell Biology, Kleinloog, Rachel, Verweij, Bon H., Van Der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., De Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, Van Der Zwan, Albert, Van Der Sprenkel, Jan W. Berkelbach, Han, K. Sen, Gosselaar, Peter, Van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Cell Biology, Neurobiology and Biophysics, Sub Cell Biology, Kleinloog, Rachel, Verweij, Bon H., Van Der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., De Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, Van Der Zwan, Albert, Van Der Sprenkel, Jan W. Berkelbach, Han, K. Sen, Gosselaar, Peter, Van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J.E., Veldink, Jan H., and Ruigrok, Ynte M.

Published
2016

37. RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture

Author

ZL Cerebrovasculaire Ziekten Medisch, Brain, Neurogenetica, ZL Algemene en Acute Nec Medisch, Opleiding Neurochirurgie, Zorglijn FNE Medisch, Neurologie, Circulatory Health, Hersenen-Medisch 2, ZL Neuromusculaire Ziekten Medisch, Kleinloog, Rachel, Verweij, Bon H., Van Der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., De Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, Van Der Zwan, Albert, Van Der Sprenkel, Jan W Berkelbach, Sen Han, K., Gosselaar, Peter, Van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J E, Veldink, Jan H., Ruigrok, Ynte M., ZL Cerebrovasculaire Ziekten Medisch, Brain, Neurogenetica, ZL Algemene en Acute Nec Medisch, Opleiding Neurochirurgie, Zorglijn FNE Medisch, Neurologie, Circulatory Health, Hersenen-Medisch 2, ZL Neuromusculaire Ziekten Medisch, Kleinloog, Rachel, Verweij, Bon H., Van Der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., De Muynck, Louis, Van Damme, Philip, Giuliani, Fabrizio, Regli, Luca, Van Der Zwan, Albert, Van Der Sprenkel, Jan W Berkelbach, Sen Han, K., Gosselaar, Peter, Van Rijen, Peter C., Korkmaz, Emine, Post, Jan A., Rinkel, Gabriel J E, Veldink, Jan H., and Ruigrok, Ynte M.

Published
2016

39. Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Author

Farlow, Janice L., Lin, Hai, Sauerbeck, Laura, Lai, Dongbing, Koller, Daniel L., Pugh, Elizabeth, Hetrick, Kurt, Ling, Hua, Kleinloog, Rachel, van der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., Verweij, Bon H., Regli, Luca, Rinkel, Gabriel J. E., Ruigrok, Ynte M., Doheny, Kimberly, Liu, Yunlong, Broderick, Joseph, Foroud, Tatiana, FIA Study Investigators, Farlow, Janice L., Lin, Hai, Sauerbeck, Laura, Lai, Dongbing, Koller, Daniel L., Pugh, Elizabeth, Hetrick, Kurt, Ling, Hua, Kleinloog, Rachel, van der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., Verweij, Bon H., Regli, Luca, Rinkel, Gabriel J. E., Ruigrok, Ynte M., Doheny, Kimberly, Liu, Yunlong, Broderick, Joseph, Foroud, Tatiana, and FIA Study Investigators

Published
2015

40. Whole blood gene expression profiles of patients with a past aneurysmal subarachnoid hemorrhage

Author

Brain, Circulatory Health, Hersenen-Medisch 2, ZL Cerebrovasculaire Ziekten Medisch, ZL Neuromusculaire Ziekten Medisch, Van't Hof, Femke N G, Ruigrok, Ynte M., Medic, Jelena, Sanjabi, Bahram, Van Der Vlies, Pieter, Rinkel, Gabriel J E, Veldink, Jan H., Etminan, Nima, Brain, Circulatory Health, Hersenen-Medisch 2, ZL Cerebrovasculaire Ziekten Medisch, ZL Neuromusculaire Ziekten Medisch, Van't Hof, Femke N G, Ruigrok, Ynte M., Medic, Jelena, Sanjabi, Bahram, Van Der Vlies, Pieter, Rinkel, Gabriel J E, Veldink, Jan H., and Etminan, Nima

Published
2015

41. Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Author

ZL Cerebrovasculaire Ziekten Medisch, Brain, Circulatory Health, Neurologie, Farlow, Janice L., Lin, Hai, Sauerbeck, Laura, Lai, Dongbing, Koller, Daniel L., Pugh, Elizabeth, Hetrick, Kurt, Ling, Hua, Kleinloog, Rachel, van der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., Verweij, Bon H., Regli, Luca, Rinkel, Gabriel J. E., Ruigrok, Ynte M., Doheny, Kimberly, Liu, Yunlong, Broderick, Joseph, Foroud, Tatiana, FIA Study Investigators, ZL Cerebrovasculaire Ziekten Medisch, Brain, Circulatory Health, Neurologie, Farlow, Janice L., Lin, Hai, Sauerbeck, Laura, Lai, Dongbing, Koller, Daniel L., Pugh, Elizabeth, Hetrick, Kurt, Ling, Hua, Kleinloog, Rachel, van der Vlies, Pieter, Deelen, Patrick, Swertz, Morris A., Verweij, Bon H., Regli, Luca, Rinkel, Gabriel J. E., Ruigrok, Ynte M., Doheny, Kimberly, Liu, Yunlong, Broderick, Joseph, Foroud, Tatiana, and FIA Study Investigators

Published
2015

43. Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism.

Author

Stolle, Sarah, Ciapaite, Jolita, Reijne, Aaffien C., Talarovicova, Alzbeta, Wolters, Justina C., Aguirre‐Gamboa, Raúl, van der Vlies, Pieter, de Lange, Kim, Neerincx, Pieter B., van der Vries, Gerben, Deelen, Patrick, Swertz, Morris A., Li, Yang, Bischoff, Rainer, Permentier, Hjalmar P., Horvatovitch, Peter L., Groen, Albert K., van Dijk, Gertjan, Reijngoud, Dirk‐Jan, and Bakker, Barbara M.

Subjects
MITOCHONDRIAL pathology, SKELETAL muscle, EXERCISE physiology, MUSCLE metabolism, MUSCLE weakness, DISEASES
Abstract

Summary: Loss of mitochondrial respiratory flux is a hallmark of skeletal muscle aging, contributing to a progressive decline of muscle strength. Endurance exercise alleviates the decrease in respiratory flux, both in humans and in rodents. Here, we dissect the underlying mechanism of mitochondrial flux decline by integrated analysis of the molecular network. Mice were given a lifelong ad libitum low‐fat or high‐fat sucrose diet and were further divided into sedentary and running‐wheel groups. At 6, 12, 18 and 24 months, muscle weight, triglyceride content and mitochondrial respiratory flux were analysed. Subsequently, transcriptome was measured by RNA‐Seq and proteome by targeted LC‐MS/MS analysis with 13C‐labelled standards. In the sedentary groups, mitochondrial respiratory flux declined with age. Voluntary running protected the mitochondrial respiratory flux until 18 months of age. Beyond this time point, all groups converged. Regulation Analysis of flux, proteome and transcriptome showed that the decline of flux was equally regulated at the proteomic and at the metabolic level, while regulation at the transcriptional level was marginal. Proteomic regulation was most prominent at the beginning and at the end of the pathway, namely at the pyruvate dehydrogenase complex and at the synthesis and transport of ATP. Further proteomic regulation was scattered across the entire pathway, revealing an effective multisite regulation. Finally, reactions regulated at the protein level were highly overlapping between the four experimental groups, suggesting a common, post‐transcriptional mechanism of muscle aging. [ABSTRACT FROM AUTHOR]

Published
2018
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46. Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome

Author

Damman, Jeffrey, primary, Bloks, Vincent W., additional, Daha, Mohamed R., additional, van der Most, Peter J., additional, Sanjabi, Bahram, additional, van der Vlies, Pieter, additional, Snieder, Harold, additional, Ploeg, Rutger J., additional, Krikke, Christina, additional, Leuvenink, Henri G.D., additional, and Seelen, Marc A., additional

Published
2015
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47. The emerging landscape of dynamic DNA methylation in early childhood.

Author

Cheng-Jian Xu, Bonder, Marc Jan, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gehring, Ulrike, Jankipersadsing, Soesma A., van der Vlies, Pieter, van Diemen, Cleo C., van Rijkom, Bianca, Just, Jocelyne, Kull, Inger, Kere, Juha, Antó, Josep Maria, Bousquet, Jean, Zhernakova, Alexandra, Wijmenga, Cisca, Annesi-Maesano, Isabella, Sunyer, Jordi, and Melén, Erik

Subjects
DNA methylation, GENETIC transcription, GENE expression, PHYSIOLOGICAL effects of tobacco, EPIGENETICS, CHILD development
Abstract

Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenomewide significance of p <1.14 x 10-7. Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease. Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life. [ABSTRACT FROM AUTHOR]

Published
2017
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48. Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD+ in medium-chain acyl-CoA dehydrogenase knockout mice.

Author

Martines, Anne-Claire M. F., Gerding, Albert, Stolle, Sarah, Vieira-Lara, Marcel A., Wolters, Justina C., Jurdzinski, Angelika, Bongiovanni, Laura, de Bruin, Alain, van der Vlies, Pieter, van der Vries, Gerben, Bloks, Vincent W., Derks, Terry G. J., Reijngoud, Dirk-Jan, and Bakker, Barbara M.

Subjects
TRANSCRIPTOMES, COENZYME A, DEHYDROGENASES, ENZYME deficiency, LABORATORY mice
Abstract

During fasting, mitochondrial fatty-acid β-oxidation (mFAO) is essential for the generation of glucose by the liver. Children with a loss-of-function deficiency in the mFAO enzyme medium-chain acyl-Coenzyme A dehydrogenase (MCAD) are at serious risk of life-threatening low blood glucose levels during fasting in combination with intercurrent disease. However, a subset of these children remains asymptomatic throughout life. In MCAD-deficient (MCAD-KO) mice, glucose levels are similar to those of wild-type (WT) mice, even during fasting. We investigated if metabolic adaptations in the liver may underlie the robustness of this KO mouse. WT and KO mice were given a high- or low-fat diet and subsequently fasted. We analyzed histology, mitochondrial function, targeted mitochondrial proteomics, and transcriptome in liver tissue. Loss of MCAD led to a decreased capacity to oxidize octanoyl-CoA. This was not compensated for by altered protein levels of the short- and long-chain isoenzymes SCAD and LCAD. In the transcriptome, we identified subtle adaptations in the expression of genes encoding enzymes catalyzing CoA- and NAD(P)(H)-involving reactions and of genes involved in detoxification mechanisms. We discuss how these processes may contribute to robustness in MCAD-KO mice and potentially also in asymptomatic human subjects with a complete loss of MCAD activity. [ABSTRACT FROM AUTHOR]

Published
2019
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49. DNA methylation in childhood asthma

Author

Mariona Bustamante, Francesco Forastiere, Henriette A. Smit, Petter Mowinckel, Marjan Kerkhof, Tari Haahtela, Martijn C. Nawijn, Raul Aguirre-Gamboa, Dan Mason, Mihai G. Netea, Cisca Wijmenga, Raf Azad, Vegard Hovland, John Wright, Josep M. Antó, Cilla Söderhäll, Pieter van der Vlies, William O.C.M. Cookson, Bianca van Rijkom, Lovisa E. Reinius, Soesma A Jankipersadsing, Leda Chatzi, Nour Baïz, Erik Melén, Daniela Porta, Olena Gruzieva, Juha Kere, Isabella Annesi-Maesano, Maties Torrent, Charles Auffray, Cleo C. van Diemen, Manolis Kogevinas, Davide Gori, Johann Pellet, Jose Ramon Bilbao, Harri Alenius, Göran Pershagen, Sabrina Llop, Miriam F. Moffatt, Nathanaël Lemonnier, Ashok Kumar, Simon Kebede Merid, Nanna Fyhrquist, Stephane Ballereau, Tiina Laatikainen, Cheng-Jian Xu, Johan C. de Jongste, Marc Jan Bonder, Judith Garcia-Aymerich, Karin C. Lødrup Carlsen, J Sunyer, Mikel Basterrechea, Dario Greco, Yang Li, Jean Bousquet, Ulrike Gehring, Catherine Laprise, Maria Pia Fantini, Rosemary R. C. McEachan, Bert Brunekreef, Stefano Guerra, Gerard H. Koppelman, Cornelis J. Vermeulen, Andréanne Morin, Carmen Iñiguez, Kai-Håkon Carlsen, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], University of Helsinki, King‘s College London, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stockholm County Council, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Keck School of Medicine [Los Angeles], University of Southern California (USC), Azienda Sanitaria Locale [ROMA] (ASL), McGill University and Genome Quebec Innovation Centre, Département des Sciences Fondamentales [Chicoutimi] (DSF), Université du Québec à Chicoutimi (UQAC), European Institute for Systems Biology and Medicine (EISBM), Arizona Respiratory Center, Radboud University Medical Center [Nijmegen], Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Dermatology, Allergology and Venereology, Clinicum, Medicum, Department of Bacteriology and Immunology, HUS Inflammation Center, One Health Chemisch, dIRAS RA-2, Pediatrics, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Matie, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charle, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Håkon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manoli, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C., Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H.

Subjects
Male, 0301 basic medicine, Allergy, Cytotoxic, T-Lymphocytes, [SDV]Life Sciences [q-bio], Respiratory System, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], CHILDREN, Immunoglobulin E, Epigenesis, Genetic, Child, POPULATION, education.field_of_study, biology, Methylation, 3. Good health, CpG site, Child, Preschool, DNA methylation, Female, BIOS Consortium, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, Population, PHENOTYPES, IMMUNITY, 03 medical and health sciences, Critical Care Medicine, Genetic, General & Internal Medicine, medicine, Humans, COHORT, Epigenetics, IGE, EXPOSURE, Preschool, education, Asthma, Science & Technology, business.industry, RHINITIS, DNA, DNA Methylation, medicine.disease, Eosinophils, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, Immunology, biology.protein, GENOMEWIDE ASSOCIATION, CpG Islands, business, COLLECTION, T-Lymphocytes, Cytotoxic, Epigenesis, Genome-Wide Association Study
Abstract

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p

Published
2018
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50. A Transcriptionally Distinct CXCL13 + CD103 + CD8 + T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer.

Author

Workel HH, Lubbers JM, Arnold R, Prins TM, van der Vlies P, de Lange K, Bosse T, van Gool IC, Eggink FA, Wouters MCA, Komdeur FL, van der Slikke EC, Creutzberg CL, Kol A, Plat A, Glaire M, Church DN, Nijman HW, and de Bruyn M

Subjects
Antigens, Neoplasm immunology, Female, Humans, Antigens, CD immunology, B-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Chemokine CXCL13 immunology, Integrin alpha Chains immunology, Ovarian Neoplasms immunology, Receptors, Transforming Growth Factor beta immunology
Abstract

The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation of tertiary lymphoid structures (TLSs). TLSs are thought to support antitumor immunity and are associated with improved prognosis. However, it remains unknown whether TLSs are formed in response to the general inflammatory character of the tumor microenvironment, or rather, are induced by (neo)antigen-specific adaptive immunity. We here report on the finding that the TGFβ-dependent CD103 + CD8 + tumor-infiltrating T-cell (TIL) subpopulation expressed and produced CXCL13. Accordingly, CD8 + T cells from peripheral blood activated in the presence of TGFβ upregulated CD103 and secreted CXCL13. Conversely, inhibition of TGFβ receptor signaling abrogated CXCL13 production. CXCL13 + CD103 + CD8 + TILs correlated with B-cell recruitment, TLSs, and neoantigen burden in six cohorts of human tumors. Altogether, our findings indicated that TGFβ plays a noncanonical role in coordinating immune responses against human tumors and suggest a potential role for CXCL13 + CD103 + CD8 + TILs in mediating B-cell recruitment and TLS formation in human tumors., (©2019 American Association for Cancer Research.)

Published
2019
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