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146 results on '"Kielbasa, Szymon M."'

1. Cancer-Associated Fibroblasts Are Key Determinants of Cancer Cell Invasion in the Earliest Stage of Colorectal Cancer

Author

Dang, Hao, Harryvan, Tom J., Liao, Chen-Yi, Danen, Erik H.J., Spalburg, Vienna N.L.N., Kielbasa, Szymon M., Mei, Hailiang, Goeman, Jelle J., de Jonge-Muller, Eveline S., Janson, Stefanus G.T., van der Reijden, Johan J., Crobach, Stijn, Hardwick, James C.H., Boonstra, Jurjen J., de Miranda, Noel F.C.C., and Hawinkels, Lukas J.A.C.

Published
2023
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2. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Author

Richard, Melissa A, Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A, Brody, Jennifer A, Irvin, Marguerite R, Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E, Jia, Yucheng, Syme, Catriona, Salfati, Elias L, Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H, Bressler, Jan, Morrison, Alanna C, Liu, Chunyu, Mendelson, Michael M, Uitterlinden, André G, van Meurs, Joyce B, Consortium, BIOS, Heijmans, Bastiaan T, Hoen, Peter AC ’t, van Meurs, Joyce, Isaacs, Aaron, Jansen, Rick, Franke, Lude, Boomsma, Dorret I, Pool, René, van Dongen, Jenny, Hottenga, Jouke J, van Greevenbroek, Marleen MJ, Stehouwer, Coen DA, van der Kallen, Carla JH, Schalkwijk, Casper G, Wijmenga, Cisca, Zhernakova, Alexandra, Tigchelaar, Ettje F, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H, van den Berg, Leonard H, van Duijn, Cornelia M, Hofman, Albert, Jhamai, P Mila, Verbiest, Michael, Suchiman, H Eka D, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Zhernakova, Dasha V, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M, Swertz, Morris A, van Zwet, Erik W, Franco, Oscar H, Zhang, Guosheng, Li, Yun, Stewart, James D, Bis, Joshua C, Psaty, Bruce M, Chen, Yii-Der Ida, Kardia, Sharon LR, Zhao, Wei, Turner, Stephen T, Absher, Devin, Aslibekyan, Stella, Starr, John M, McRae, Allan F, Hou, Lifang, Just, Allan C, Schwartz, Joel D, Vokonas, Pantel S, Menni, Cristina, Spector, Tim D, Shuldiner, Alan, Damcott, Coleen M, Rotter, Jerome I, Palmas, Walter, Liu, Yongmei, and Paus, Tomáš

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Aged, Blood Pressure, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Genetic Variation, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Middle Aged, Nerve Tissue Proteins, Quantitative Trait Loci, Tetraspanins, BIOS Consortium, DNA methylation, Mendelian randomization, blood pressure, epigenome-wide association study, gene expression, sequence variation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p  30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Published
2017

3. Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression.

Author

de Bruin, Ruben G, Shiue, Lily, Prins, Jurriën, de Boer, Hetty C, Singh, Anjana, Fagg, W Samuel, van Gils, Janine M, Duijs, Jacques MGJ, Katzman, Sol, Kraaijeveld, Adriaan O, Böhringer, Stefan, Leung, Wai Y, Kielbasa, Szymon M, Donahue, John P, van der Zande, Patrick HJ, Sijbom, Rick, van Alem, Carla MA, Bot, Ilze, van Kooten, Cees, Jukema, J Wouter, Van Esch, Hilde, Rabelink, Ton J, Kazan, Hilal, Biessen, Erik AL, Ares, Manuel, van Zonneveld, Anton Jan, and van der Veer, Eric P

Subjects
Monocytes, Macrophages, Foam Cells, Animals, Humans, Mice, RNA-Binding Proteins, RNA, Messenger, Cell Differentiation, Gene Expression Regulation, RNA Splicing, Models, Biological, Models, Genetic, Atherosclerosis, Genetics, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, RNA, Messenger, Models, Biological, Genetic
Abstract

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.

Published
2016

4. Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults

Author

Heijmans, Bastiaan T., ’t Hoen, Peter A.C., van Meurs, Joyce, Isaacs, Aaron, Jansen, Rick, Franke, Lude, Boomsma, Dorret I., Pool, René, van Dongen, Jenny, Hottenga, Jouke J., van Greevenbroek, Marleen M.J., Stehouwer, Coen D.A., van der Kallen, Carla J.H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., Hof, Peter van ’t, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Hoen, Peter-Bram ’t, Zilhão, Nuno R., Sugden, Karen, Hannon, Eilis J., Mill, Jonathan, Caspi, Avshalom, Agnew-Blais, Jessica, Arseneault, Louise, Corcoran, David L., Moffitt, Terrie E., Poulton, Richie, and Franke, Barbara

Published
2019
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7. Correction: Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge

Author

Voskamp, Astrid L., primary, Tak, Tamar, additional, Gerdes, Maarten L., additional, Menafra, Roberta, additional, Duijster, Ellen, additional, Jochems, Simon P., additional, Kielbasa, Szymon M., additional, Kormelink, Tom Groot, additional, Stam, Koen A., additional, van Hengel, Oscar R.J., additional, de Jong, Nicolette W., additional, Hendriks, Rudi W., additional, Kloet, Susan L., additional, Yazdanbakhsh, Maria, additional, de Jong, Esther C., additional, Gerth van Wijk, Roy, additional, and Smits, Hermelijn H., additional

Published
2023
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8. Acquisition of a Glycosylated B-Cell Receptor Drives Follicular Lymphoma Towards a Dark Zone Phenotype

Author

Van Bergen, Cornelis A.M., primary, Kloet, Susan L., additional, Quinten, Edwin, additional, Sepúlveda Yáñez, Julieta Haydee, additional, Menafra, Roberta, additional, Griffioen, Marieke, additional, Jansen, Patty M, additional, Koning, Marvyn T., additional, Knijnenburg, Jeroen, additional, Navarrete, Marcelo A, additional, Kielbasa, Szymon M., additional, and Veelken, Hendrik, additional

Published
2023
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9. Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge

Author

Voskamp, Astrid L., primary, Tak, Tamar, additional, Gerdes, Maarten L., additional, Menafra, Roberta, additional, Duijster, Ellen, additional, Jochems, Simon P., additional, Kielbasa, Szymon M., additional, Kormelink, Tom Groot, additional, Stam, Koen A., additional, van Hengel, Oscar R.J., additional, de Jong, Nicolette W., additional, Hendriks, Rudi W., additional, Kloet, Susan L., additional, Yazdanbakhsh, Maria, additional, de Jong, Esther C., additional, Gerth van Wijk, Roy, additional, and Smits, Hermelijn H., additional

Published
2023
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10. Eleven grand challenges in single-cell data science

Author

Lähnemann, David, Köster, Johannes, Szczurek, Ewa, McCarthy, Davis J., Hicks, Stephanie C., Robinson, Mark D., Vallejos, Catalina A., Campbell, Kieran R., Beerenwinkel, Niko, Mahfouz, Ahmed, Pinello, Luca, Skums, Pavel, Stamatakis, Alexandros, Attolini, Camille Stephan-Otto, Aparicio, Samuel, Baaijens, Jasmijn, Balvert, Marleen, Barbanson, Buys de, Cappuccio, Antonio, Corleone, Giacomo, Dutilh, Bas E., Florescu, Maria, Guryev, Victor, Holmer, Rens, Jahn, Katharina, Lobo, Thamar Jessurun, Keizer, Emma M., Khatri, Indu, Kielbasa, Szymon M., Korbel, Jan O., Kozlov, Alexey M., Kuo, Tzu-Hao, Lelieveldt, Boudewijn P.F., Mandoiu, Ion I., Marioni, John C., Marschall, Tobias, Mölder, Felix, Niknejad, Amir, Rączkowska, Alicja, Reinders, Marcel, Ridder, Jeroen de, Saliba, Antoine-Emmanuel, Somarakis, Antonios, Stegle, Oliver, Theis, Fabian J., Yang, Huan, Zelikovsky, Alex, McHardy, Alice C., Raphael, Benjamin J., Shah, Sohrab P., and Schönhuth, Alexander

Published
2020
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11. Supplemental Methods, Supplementary Figures 1-4, Supplementary Table 1 from Integrated Whole Genome and Transcriptome Analysis Identified a Therapeutic Minor Histocompatibility Antigen in a Splice Variant of ITGB2

Author

Pont, Margot J., primary, van der Lee, Dyantha I., primary, van der Meijden, Edith D., primary, van Bergen, Cornelis A.M., primary, Kester, Michel G.D., primary, Honders, Maria W., primary, Vermaat, Martijn, primary, Eefting, Matthias, primary, Marijt, Erik W.A., primary, Kielbasa, Szymon M., primary, Hoen, Peter A.C. 't, primary, Falkenburg, J.H. Frederik, primary, and Griffioen, Marieke, primary

Published
2023
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13. Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas

Author

Kleiburg, Fleur, Heijmen, Linda, Gelderblom, Hans, Kielbasa, Szymon M., Bovée, Judith Vmg, and de Geus-Oei, L.F.

Abstract

Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor prognosis due to limited response rates to chemotherapy. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may offer a new perspective. PSMA is a type II transmembrane glycoprotein which is present in all prostatic tissue and overexpressed in prostate cancer. Despite the name, PSMA is not prostate-specific. PSMA expression is also found in a multitude of non-prostatic diseases including a subgroup of sarcomas, mostly in its neovascular endothelial cells. On PET/CT imaging, multiple sarcomas have also shown intense PSMA-tracer accumulation. PSMA expression and PSMA-tracer uptake seem to be highest in patients with aggressive and advanced sarcomas, who are also in highest need of new therapeutic options. Although these results provide a good rationale for the future use of PSMA-targeted radioligand therapy in a selection of sarcoma patients, more research is needed to gain insight into optimal patient selection methods, PSMA-targeting antibodies and tracers, administered doses of radioligand therapy, and their efficacy and tolerability. In this review, mRNA expression of the FOLH1 gene which encodes PSMA, PSMA immunohistochemistry, PSMA-targeted imaging and PSMA-targeted therapy in sarcomas will be discussed.

Published
2023

16. Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model

Author

Toonen, Lodewijk J. A., Overzier, Maurice, Evers, Melvin M., Leon, Leticia G., van der Zeeuw, Sander A. J., Mei, Hailiang, Kielbasa, Szymon M., Goeman, Jelle J., Hettne, Kristina M., Magnusson, Olafur Th., Poirel, Marion, Seyer, Alexandre, ‘t Hoen, Peter A. C., and van Roon-Mom, Willeke M. C.

Published
2018
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17. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Author

Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Johannesson, Magnus, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chris, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, Day, Felix R., Mills, M. C., Tropf, F. C., Brazel, D. M., van Zuydam, N., Vaez, A., Agbessi, M., Ahsan, H., Alves, I., Andiappan, A. K., Arindrarto, W., Awadalla, P., Battle, A., Beutner, F., Jan Bonder, M., Boomsma, D. I., Christiansen, M. W., Claringbould, A., Deelen, P., Esko, T., Fave, M. -J., Franke, L., Frayling, T., Gharib, S. A., Gibson, G., Heijmans, B. T., Hemani, G., Jansen, R., Kahonen, M., Kalnapenkis, A., Kasela, S., Kettunen, J., Kim, Y., Kirsten, H., Kovacs, P., Krohn, K., Kronberg, J., Kukushkina, V., Kutalik, Z., Lee, B., Lehtimaki, T., Loeffler, M., Marigorta, U. M., Mei, H., Milani, L., Montgomery, G. W., Muller-Nurasyid, M., Nauck, M., Nivard, M. G., Penninx, B. W. J. H., Perola, M., Pervjakova, N., Pierce, B. L., Powell, J., Prokisch, H., Psaty, B. M., Raitakari, O. T., Ripatti, S., Rotzschke, O., Rueger, S., Saha, A., Scholz, M., Schramm, K., Seppala, I., Slagboom, E. P., Stehouwer, C. D. A., Stumvoll, M., Sullivan, P., 't Hoen, P. A. C., Teumer, A., Thiery, J., Tong, L., Tonjes, A., van Dongen, J., van Iterson, M., van Meurs, J., Veldink, J. H., Verlouw, J., Visscher, P. M., Volker, U., Vosa, U., Westra, H. -J., Wijmenga, C., Yaghootkar, H., Yang, J., Zeng, B., Zhang, F., van Greevenbroek, M. M. J., Schalkwijk, C. G., Deelen, J., van Heemst, D., van Duijn, C. M., Hofman, B. A., Isaacs, A., Uitterlinden, A. G., Verbiest, M., Suchiman, H. E. D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Bot, J., Zhernakova, D. V., Luijk, R., Bonder, M. J., Swertz, M. A., van Zwet, E. W., Akimova, E. T., Bergmann, S., Boardman, J. D., Buring, J. E., Cesarini, D., Chasman, D. I., Chavarro, J. E., Cocca, M., Concas, M. P., Davey-Smith, G., Davies, G., Deary, I. J., Gaskins, A. J., de Geus, E. J. C., Gieger, C., Girotto, G., Grabe, H. J., Gunderson, E. P., Harris, K. M., Hartwig, F. P., He, C., Homuth, G., Horta, B. L., Jan Hottenga, J., Huang, H., Hyppӧnen, E., Ikram, M. A., Johannesson, M., Kamali, Z., Kavousi, M., Kraft, P., Kuhnel, B., Langenberg, C., Study, L. C., Lind, P. A., Luan, J., Magi, R., Magnusson, P. K. E., Mahajan, A., Martin, N. G., Mbarek, H., Mccarthy, M. I., Mcmahon, G., Mcqueen, M. B., Medland, S. E., Meitinger, T., Metspalu, A., Mihailov, E., Missmer, S. A., Mollegaard, S., Mook-Kanamori, D. O., Morgan, A., van der Most, P. J., de Mutsert, R., Noordam, R., Power, C., Redmond, P., Rich-Edwards, J. W., Ridker, P. M., Rietveld, C. A., Ring, S. M., Rose, L. M., Rueedi, R., Stefansson, K., Stockl, D., Strauch, K., Thurik, A. R., Timpson, N. J., Turman, C., Wareham, N. J., Willemsen, G., Zhao, J. H., Pers, T. H., Snieder, H., Perry, J. R. B., Ong, K. K., den Hoed, M., Barban, N., Day, F. R., Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Hyppӧnen, Elina, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Consortium, eQTLGen, Consortium, BIOS, Consortium, Human Reproductive Behaviour, Mahajan, A, McCarthy, MI, Mills, Melinda C., Tropf, Felix C., Brazel, David M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Marku, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Jori, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthij, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Ikram, M. Arfan, Johannesson, Magnu, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thoma, Metspalu, Andre, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chri, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Dori, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Perry, John R. B., Ong, Ken K., Day, Felix R., Sociology [until 2010], Biological Psychology, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Management and Organisation, Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Neurology, Applied Economics, and Life Course Epidemiology (LCE)

Subjects
Male, demography, genetic variants, reproductive biology, externalising behavior, environmental effects, Disease, Genome-wide association studies, Behavioral Neuroscience, 0302 clinical medicine, genetics, media_common, fertility, 0303 health sciences, Reproduction, Incidence (epidemiology), Coitus, Age Factors, Longevity, sexual intercourse, health, Spermatid differentiation, Single Nucleotide, Reproduction/genetics, 3. Good health, Behavioural genetics, Parturition/genetics, Female, infertility, Infertility, genetic variant, Adolescent, Social Psychology, media_common.quotation_subject, Experimental and Cognitive Psychology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Reproductive biology, medicine, Humans, Polymorphism, behavioural genetics, first sexual intercourse, Genetic Association Studies, Demography, 030304 developmental biology, Parturition, Coitus/physiology, medicine.disease, externalising behaviour, Sexual intercourse, Fertility, age, 030217 neurology & neurosurgery, first birth
Abstract

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Published
2021

19. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Author

Hop, Paul J., Zwamborn, Ramona A. J., Hannon, Eilis, Shireby, Gemma L., Nabais, Marta F., Walker, Emma M., van Rheenen, Wouter, van Vugt, Joke J. F. A., Dekker, Annelot M., Westeneng, Henk-Jan, Tazelaar, Gijs H. P., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, Andre G., van Eijk, Kristel R., van Meurs, Joyce, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, Moisse, Matthieu, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., Jansen, Rick, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, t Hoen, Peter A. C., Heijmans, Bastiaan T., Moed, Matthijs, Baird, Denis, Franke, Lude, Vermaat, Martijn, Luijk, Rene, Jan Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Al Khleifat, Ahmad, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik W., Al-Chalabi, Ammar, Wray, Naomi R., Bensimon, Gilbert, Hardiman, Orla, Iacoangeli, Alfredo, Chio, Adriano, Smith, George Davey, Mill, Jonathan, Ticozzi, Nicola, Ratti, Antonia, Cooper-Knock, Jonathan, Morrison, Karen E., Shaw, Pamela J., Basak, A. Nazli, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Canosa, Antonio, Brunetti, Maura, Grassano, Maurizio, Gotkine, Marc, Lerner, Yossef, Zabari, Michal, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Mora Pardina, Jesus S., Salas, Teresa, Dion, Patrick, Ross, Jay P., Henderson, Robert D., Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Nicholson, Garth, Rowe, Dominic B., Pamphlett, Roger, Mather, Karen A., Sachdev, Perminder S., Furlong, Sarah, Garton, Fleur C., Henders, Anjali K., Lin, Tian, Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Williams, Kelly L., Neto, Miguel Mitne, Cauchi, Ruben J., Blair, Ian P., Kiernan, Matthew C., Drory, Vivian, Povedano, Monica, Carvalho, Mamede, Pinto, Susana, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Landers, John E., Shaw, Christopher E., Andersen, Peter M., McRae, Allan F., van Es, Michael A., Pasterkamp, R. Jeroen, McLaughlin, Russell L., Kenna, Kevin P., Tsai, Ellen, Runz, Heiko, Van Damme, Philip, Boomsma, Dorret I., Pool, Rene, van Dongen, Jenny, Hottenga, Joukje J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D.A., van der Kallen, Carla J.H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Laboratory Medicine, APH - Mental Health, Internal Medicine, Epidemiology, and Repositório da Universidade de Lisboa

Subjects
Cholesterol, Amyotrophic Lateral Sclerosis, Humans, Neurodegenerative Diseases, General Medicine, DNA Methylation, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Article, Epigenesis, Genetic, Genome-Wide Association Study
Abstract

Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works., Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions., The research reported in this publication was supported by grants from The Dutch Research Council (NWO) (VENI scheme grant 09150161810018 to W.v.R.) and Prinses Beatrix Spierfond (neuromuscular fellowship grant W.F19-03 to W.v.R.), The Prinses Beatrix Spierfonds (W.OR20-08 to J.J.F.A.v.V. and J.H.V.), The Canadian Institutes of Health Research (FRN 159279 to J.P.R.), The Dutch Research Council (NWO) (VIDI grant 91719350 to K.P.K.), The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 772376-EScORIAL to J.H.V.), the Swedish Brain Foundation (grant nos. 2012-0262, 2012-0305, 2013-0279, 2016-0303, 2018-0310, and 2020-0353 to P.M.A.), the Swedish Research Council (grant nos. 2012-3167 and 2017-03100 to P.M.A.), the Knut and Alice Wallenberg Foundation (grant nos. 2012.0091, 2014.0305, and 2020.0232 to P.M.A.), the Ulla-Carin Lindquist Foundation and the Västerbotten County Council (grant no. 56103-7002829 to P.M.A.), and King Gustaf V’s and Queen Victoria’s Freemason’s Foundation. This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND (www.jpnd.eu) [United Kingdom, Medical Research Council (MR/L501529/1; MR/R024804/1) and Economic and Social Research Council (ES/L008238/1)] and through the Motor Neurone Disease Association (MNDA). This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. A.A.-C. is supported by an NIHR Senior Investigator Award. Samples used in this research were entirely/in part obtained from the U.K. National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. We would like to thank people with MND and their families for their participation in this project. We acknowledge sample management undertaken by Biobanking Solutions funded by the Medical Research Council at the Centre for Integrated Genomic Medical Research, University of Manchester. R.J.P. is funded through the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (BRAINSCAPES). G.L.S. was supported by a PhD studentship from the Alzheimer’s Society. S.T.N. acknowledges support through a FightMND Mid-Career Fellowship. V.S. is supported by the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. A.A.K. is funded by the MNDA and NIHR Maudsley Biomedical Research Centre. D.B., E.T., and H.R. are employees of Biogen. L.H.v.d.B. reports grants from the Netherlands ALS Foundation, grants from The Netherlands Organization for Health Research and Development (Vici scheme), grants from The European Community’s Health Seventh Framework Programme [grant agreement no. 259867 (EuroMOTOR) to L.H.v.d.B.], and grants from The Netherlands Organization for Health Research and Development (the STRENGTH project, funded through the EU Joint Programme–Neurodegenerative Disease Research, JPND), during the conduct of the study. Project MinE Belgium was supported by a grant from IWT (no. 140935), the ALS Liga België, the National Lottery of Belgium, and the KU Leuven Opening the Future Fund. P.V.D. holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België, and the KU Leuven funds “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek”, and the “Valéry Perrier Race against ALS Fund”. This work was supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, grant RF-2016-02362405 to A. Chiò), the Progetti di Rilevante Interesse Nazionale program of the Ministry of Education, University and Research (grant 2017SNW5MB to A. Chiò); the European Commission’s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867 to A. Chiò), and the Joint Programme–Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by Italian Ministry of Education, University, and Research. This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the “Rita Levi Montalcini” Department of Neuroscience, University of Torino, Italy. We acknowledge funding from the Australian National Health and Medical Research (NHMRC) Council: 1151854, 1083187, 1173790, 1078901, 1113400, 1095215, and 1176913 Enabling Grant #402703 to N.R.W. Additional funding was provided by the Motor Neurone Disease Research Institute of Australia Ice Bucket Challenge grant for the SALSA-SGC consortium. The OATS (used for controls) was facilitated through Twins Research Australia, a national resource in part supported by a Centre for Research Excellence from the Australian NHMRC Council (NHMRC 1079102 to N.R.W.). Funding for this study was awarded by the (NHMRC)/Australian Research Council Strategic Award (grant 401162 to N.R.W.) and NHMRC grants (1405325, 1024224, 1025243, 1045325, 1085606, 568969, and 1093083 to N.R.W.). The collaboration project is cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This study was supported by the ALS Foundation Netherlands. This work was sponsored by NWO Domain Science for the use of the national computer facilities. A.N.B. is grateful to the Suna and Inan Kirac Foundation and Koc University for the excellent research environment created and for financial support. G.A.R. is supported by the Canadian Institutes of Health. Several authors of this publication are members of the Netherlands Neuromuscular Center (NL-NMD) and the European Reference Network for rare neuromuscular diseases EURO-NMD. French ALS patients of the Pitié-Salpêtrière hospital (Paris) have been collected with ARSla funding support.

Published
2022

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

Author

van Dongen, Jenny, Hagenbeek, Fiona A., Suderman, Matthew, Roetman, Peter J., Sugden, Karen, Chiocchetti, Andreas G., Ismail, Khadeeja, Mulder, Rosa H., Hafferty, Jonathan D., Adams, Mark J., Walker, Rosie M., Morris, Stewart W., Lahti, Jari, Küpers, Leanne K., Escaramis, Georgia, Alemany, Silvia, Jan Bonder, Marc, Meijer, Mandy, Ip, Hill F., Jansen, Rick, Baselmans, Bart M. L., Parmar, Priyanka, Lowry, Estelle, Streit, Fabian, Sirignano, Lea, Send, Tabea S., Frank, Josef, Jylhävä, Juulia, Wang, Yunzhang, Mishra, Pashupati Prasad, Colins, Olivier F., Corcoran, David L., Poulton, Richie, Mill, Jonathan, Hannon, Eilis, Arseneault, Louise, Korhonen, Tellervo, Vuoksimaa, Eero, Felix, Janine F., Bakermans-Kranenburg, Marian J., Campbell, Archie, Czamara, Darina, Binder, Elisabeth, Corpeleijn, Eva, Gonzalez, Juan R., Grazuleviciene, Regina, Gutzkow, Kristine B., Evandt, Jorunn, Vafeiadi, Marina, Klein, Marieke, van der Meer, Dennis, Ligthart, Lannie, Heijmans, Bastiaan T., ’t Hoen, Peter A. C., van Meurs, Joyce, Franke, Lude, Boomsma, Dorret I., Pool, René, Hottenga, Jouke J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D. A., van der Kallen, Carla J. H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., ’t Hoen, Peter-Bram, Kluft, Cornelis, Davies, Gareth E., Hakulinen, Christian, Keltikangas-Järvinen, Liisa, Franke, Barbara, Freitag, Christine M., Konrad, Kerstin, Hervas, Amaia, Fernández-Rivas, Aranzazu, Vetro, Agnes, Raitakari, Olli, Lehtimäki, Terho, Vermeiren, Robert, Strandberg, Timo, Räikkönen, Katri, Snieder, Harold, Witt, Stephanie H., Deuschle, Michael, Pedersen, Nancy L., Hägg, Sara, Sunyer, Jordi, Kaprio, Jaakko, Ollikainen, Miina, Moffitt, Terrie E., Tiemeier, Henning, van IJzendoorn, Marinus H., Relton, Caroline, Vrijheid, Martine, Sebert, Sylvain, Jarvelin, Marjo-Riitta, Caspi, Avshalom, Evans, Kathryn L., McIntosh, Andrew M., Bartels, Meike, Child and Adolescent Psychiatry / Psychology, Pediatrics, Internal Medicine, Urology, Epidemiology, Orthopedics and Sports Medicine, Clinical Child and Family Studies, van der Kallen, Carla J. H., Schalkwijk, Casper G., Wijmenga, Cisca, Franke, Lude, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., van Meurs, Joyce, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., Jansen, Rick, van 't Hof, Peter, Deelen, Patrick, Nooren, Irene, 't Hoen, Peter A. C., Heijmans, Bastiaan T., Moed, Matthijs, Vermaat, Martijn, Luijk, René, Jan Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik W., 't Hoen, Peter-Bram, Boomsma, Dorret I., Pool, René, van Dongen, Jenny, Hottenga, Jouke J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D. A., Institute for Molecular Medicine Finland, University of Helsinki, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Faculty of Medicine, Tellervo Korhonen / Principal Investigator, Genetic Epidemiology, Faculty Common Matters (Faculty of Medicine), Cognitive and Brain Aging, Helsinki Inequality Initiative (INEQ), Psychosocial factors and health, Faculty Common Matters (Faculty of Education), Medicum, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, Geriatrian yksikkö, Reproductive Origins of Adult Health and Disease (ROAHD), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Pediatric surgery, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), APH - Personalized Medicine, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Tampere University, Health Sciences, Department of Clinical Chemistry, Clinical Medicine, RS: MHeNs - R2 - Mental Health, and Psychiatrie & Neuropsychologie

Subjects
0301 basic medicine, Molecular biology, ADN, Physiology, CHILDREN, 3124 Neurology and psychiatry, Epigenesis, Genetic, Epigenome, 0302 clinical medicine, Child, RISK, ASSOCIATION, Middle Aged, Justice and Strong Institutions, Aggression, Psychiatry and Mental health, Schizophrenia, TWINS, Meta-analysis, Cord blood, Child, Preschool, DNA methylation, HEALTH, medicine.symptom, SMOKING, Adult, SDG 16 - Peace, Adolescent, 515 Psychology, Longevity, Biology, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Genetics, Humans, ddc:610, EXPOSURE, ABUSE, Genetic association, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], SDG 16 - Peace, Justice and Strong Institutions, 3112 Neurosciences, GENOME-WIDE, DNA Methylation, Epigenètica, medicine.disease, 3141 Health care science, 030104 developmental biology, COHORT PROFILE, 1182 Biochemistry, cell and molecular biology, CpG Islands, 3111 Biomedicine, Metaanàlisi, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Molecular psychiatry 26(6), 2148-2162 (2021). doi:10.1038/s41380-020-00987-x, Published by Macmillan, London

Published
2021

21. "Snapshotting" Somatic Hypermutation in Single Follicular Lymphoma Cells

Author

Sepulveda-Yanez, Juleta H., primary, Alvarez-Saravia, Diego, additional, Quinten, Edwin, additional, Menafra, Roberta, additional, Kloet, Susan L., additional, Monajemi, Ramin, additional, Kielbasa, Szymon M., additional, Navarrete Signorile, Marcelo, additional, van Bergen, Cornelis A.M., additional, and Veelken, Hendrik, additional

Published
2021
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22. Hippocampal glucocorticoid target genes associated with enhancement of memory consolidation

Author

Buurstede, Jacobus C., primary, van Weert, Lisa T.C.M., additional, Colucci, Paola, additional, Gentenaar, Max, additional, Viho, Eva M.G., additional, Koorneef, Lisa L., additional, Schoonderwoerd, Robin A., additional, Lanooij, Suzanne D., additional, Moustakas, Ioannis, additional, Balog, Judit, additional, Mei, Hailiang, additional, Kielbasa, Szymon M., additional, Campolongo, Patrizia, additional, Roozendaal, Benno, additional, and Meijer, Onno C., additional

Published
2021
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23. Hippocampal glucocorticoid target genes associated with enhancement of memory consolidation.

Author

Buurstede, Jacobus C., van Weert, Lisa T.C.M., Colucci, Paola, Gentenaar, Max, Viho, Eva M.G., Koorneef, Lisa L., Schoonderwoerd, Robin A., Lanooij, Suzanne D., Moustakas, Ioannis, Balog, Judit, Mei, Hailiang, Kielbasa, Szymon M., Campolongo, Patrizia, Roozendaal, Benno, and Meijer, Onno C.

Subjects
GLUCOCORTICOIDS, GLUCOCORTICOID receptors, LONG-term memory, HIPPOCAMPUS (Brain), MEMORY
Abstract

Glucocorticoids enhance memory consolidation of emotionally arousing events via largely unknown molecular mechanisms. This glucocorticoid effect on the consolidation process also requires central noradrenergic neurotransmission. The intracellular pathways of these two stress mediators converge on two transcription factors: the glucocorticoid receptor (GR) and phosphorylated cAMP response element‐binding protein (pCREB). We therefore investigated, in male rats, whether glucocorticoid effects on memory are associated with genomic interactions between the GR and pCREB in the hippocampus. In a two‐by‐two design, object exploration training or no training was combined with post‐training administration of a memory‐enhancing dose of corticosterone or vehicle. Genomic effects were studied by chromatin immunoprecipitation followed by sequencing (ChIP‐seq) of GR and pCREB 45 min after training and transcriptome analysis after 3 hr. Corticosterone administration induced differential GR DNA‐binding and regulation of target genes within the hippocampus, largely independent of training. Training alone did not result in long‐term memory nor did it affect GR or pCREB DNA‐binding and gene expression. No strong evidence was found for an interaction between GR and pCREB. Combination of the GR DNA‐binding and transcriptome data identified a set of novel, likely direct, GR target genes that are candidate mediators of corticosterone effects on memory consolidation. Cell‐specific expression of the identified target genes using single‐cell expression data suggests that the effects of corticosterone reflect in part non‐neuronal cells. Together, our data identified new GR targets associated with memory consolidation that reflect effects in both neuronal and non‐neuronal cells. [ABSTRACT FROM AUTHOR]

Published
2022
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24. Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens

Author

Fuchs, Kyra J., Honders, M. Willy, van der Meijden, Edith D., Adriaans, Alwin E., van der Lee, Dyantha I., Pont, Margot J., Monajemi, Ramin, Kielbasa, Szymon M., ’t Hoen, Peter A. C., van Bergen, Cornelis A. M., Falkenburg, J. H. Frederik, and Griffioen, Marieke

Subjects
Medizinische Fakultät, ddc:610
Abstract

Patients undergoing allogeneic stem cell transplantation as treatment for hematological diseases face the risk of Graft-versus-Host Disease as well as relapse. Graft-versus-Host Disease and the favorable Graft-versus-Leukemia effect are mediated by donor T cells recognizing polymorphic peptides, which are presented on the cell surface by HLA molecules and result from single nucleotide polymorphism alleles that are disparate between patient and donor. Identification of polymorphic HLA-binding peptides, designated minor histocompatibility antigens, has been a laborious procedure, and the number and scope for broad clinical use of these antigens therefore remain limited. Here, we present an optimized whole genome association approach for discovery of HLA class I minor histocompatibility antigens. T cell clones isolated from patients who responded to donor lymphocyte infusions after HLA-matched allogeneic stem cell transplantation were tested against a panel of 191 EBV-transformed B cells, which have been sequenced by the 1000 Genomes Project and selected for expression of seven common HLA class I alleles (HLA-A∗01:01, A∗02:01, A∗03:01, B∗07:02, B∗08:01, C∗07:01, and C∗07:02). By including all polymorphisms with minor allele frequencies above 0.01, we demonstrated that the new approach allows direct discovery of minor histocompatibility antigens as exemplified by seven new antigens in eight different HLA class I alleles including one antigen in HLA-A∗24:02 and HLA-A∗23:01, for which the method has not been originally designed. Our new whole genome association strategy is expected to rapidly augment the repertoire of HLA class I-restricted minor histocompatibility antigens that will become available for donor selection and clinical use to predict, follow or manipulate Graft-versus-Leukemia effect and Graft-versus-Host Disease after allogeneic stem cell transplantation.

Published
2020

25. Nasal systems immunology identifies inflammatory and tolerogenic myeloid cells that determine allergic outcome following challenge

Author

Voskamp, Astrid L., primary, Gerdes, Maarten L., additional, Menafra, Roberta, additional, Duijster, Ellen, additional, Kielbasa, Szymon M., additional, Kormelink, Tom Groot, additional, Tak, Tamar, additional, Stam, Koen A., additional, de Jong, Nicolette W., additional, Hendriks, Rudi W., additional, Kloet, Suzanne L., additional, Yazdanbakhsh, Maria, additional, de Jong, Esther C., additional, Gerth van Wijk, Roy, additional, and Smits, Hermelijn H., additional

Published
2020
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26. Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies

Author

Hammerschlag, Anke R., primary, Byrne, Enda M., additional, Bartels, Meike, additional, Wray, Naomi R., additional, Middeldorp, Christel M., additional, Agbessi, Mawussé, additional, Ahsan, Habibul, additional, Alves, Isabel, additional, Andiappan, Anand, additional, Arindrarto, Wibowo, additional, Awadalla, Philip, additional, Battle, Alexis, additional, Beutner, Frank, additional, Bonder, Marc Jan, additional, Boomsma, Dorret I., additional, Christiansen, Mark, additional, Claringbould, Annique, additional, Deelen, Patrick, additional, Esko, Tõnu, additional, Favé, Marie-Julie, additional, Franke, Lude, additional, Frayling, Timothy, additional, Gharib, Sina A., additional, Gibson, Gregory, additional, Heijmans, Bastiaan T., additional, Hemani, Gibran, additional, Jansen, Rick, additional, Kähönen, Mika, additional, Kalnapenkis, Anette, additional, Kasela, Silva, additional, Kettunen, Johannes, additional, Kim, Yungil, additional, Kirsten, Holger, additional, Kovacs, Peter, additional, Krohn, Knut, additional, Kronberg-Guzman, Jaanika, additional, Kukushkina, Viktorija, additional, Kutalik, Zoltan, additional, Lee, Bernett, additional, Lehtimäki, Terho, additional, Loeffler, Markus, additional, Marigorta, Urko M., additional, Mei, Hailang, additional, Milani, Lili, additional, Montgomery, Grant W., additional, Müller-Nurasyid, Martina, additional, Nauck, Matthias, additional, Nivard, Michel, additional, Penninx, Brenda, additional, Perola, Markus, additional, Pervjakova, Natalia, additional, Pierce, Brandon L., additional, Powell, Joseph, additional, Prokisch, Holger, additional, Psaty, Bruce M., additional, Raitakari, Olli T., additional, Ripatti, Samuli, additional, Rotzschke, Olaf, additional, Rüeger, Sina, additional, Saha, Ashis, additional, Scholz, Markus, additional, Schramm, Katharina, additional, Seppälä, Ilkka, additional, Slagboom, Eline P., additional, Stehouwer, Coen D.A., additional, Stumvoll, Michael, additional, Sullivan, Patrick, additional, ‘t Hoen, Peter A.C., additional, Teumer, Alexander, additional, Thiery, Joachim, additional, Tong, Lin, additional, Tönjes, Anke, additional, van Dongen, Jenny, additional, van Iterson, Maarten, additional, van Meurs, Joyce, additional, Veldink, Jan H., additional, Verlouw, Joost, additional, Visscher, Peter M., additional, Völker, Uwe, additional, Võsa, Urmo, additional, Westra, Harm-Jan, additional, Wijmenga, Cisca, additional, Yaghootkar, Hanieh, additional, Yang, Jian, additional, Zeng, Biao, additional, Zhang, Futao, additional, Isaacs, Aaron, additional, Pool, René, additional, Hottenga, Jouke J., additional, van Greevenbroek, Marleen MJ., additional, van der Kallen, Carla J.H., additional, Schalkwijk, Casper G., additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje F., additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, van Heemst, Diana, additional, van den Berg, Leonard H., additional, van Duijn, Cornelia M., additional, Hofman, Bert A., additional, Uitterlinden, André G., additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H.Eka D., additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Daria V., additional, Hof, Peter van ‘t, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, van Dijk, Freerk, additional, Kielbasa, Szymon M., additional, Swertz, Morris A., additional, van Zwet, Erik. W., additional, and Hoen, Peter-Bram ‘t, additional

Published
2020
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27. Optimized Whole Genome Association Scanning for Discovery of HLA Class I-Restricted Minor Histocompatibility Antigens

Author

Fuchs, Kyra J., primary, Honders, M. Willy, additional, van der Meijden, Edith D., additional, Adriaans, Alwin E., additional, van der Lee, Dyantha I., additional, Pont, Margot J., additional, Monajemi, Ramin, additional, Kielbasa, Szymon M., additional, ’t Hoen, Peter A. C., additional, van Bergen, Cornelis A. M., additional, Falkenburg, J. H. Frederik, additional, and Griffioen, Marieke, additional

Published
2020
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28. High-Throughput BCR Sequencing and Single-Cell Transcriptomics Reveal Distinct Transcriptional Profiles Associated with Subclonal Evolution of Follicular Lymphoma

Author

van Bergen, Cornelis A.M., primary, Koning, Marvyn T., primary, Quinten, Edwin, primary, Mykowiecka, Agnieszka, primary, Sepulveda, Julieta, primary, Monajemi, Ramin, primary, De Groen, Ruben A.L., primary, Vermaat, Joost, primary, Kloet, Susan L., primary, Kielbasa, Szymon M., primary, Navarrete, Marcelo A., primary, Górecki, Pawel, primary, and Veelken, Hendrik, primary

Published
2019
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29. Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults

Author

van Dongen, Jenny, primary, Zilhão, Nuno R., additional, Sugden, Karen, additional, Hannon, Eilis J., additional, Mill, Jonathan, additional, Caspi, Avshalom, additional, Agnew-Blais, Jessica, additional, Arseneault, Louise, additional, Corcoran, David L., additional, Moffitt, Terrie E., additional, Poulton, Richie, additional, Franke, Barbara, additional, Boomsma, Dorret I., additional, Heijmans, Bastiaan T., additional, ’t Hoen, Peter A.C., additional, van Meurs, Joyce, additional, Isaacs, Aaron, additional, Jansen, Rick, additional, Franke, Lude, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke J., additional, van Greevenbroek, Marleen M.J., additional, Stehouwer, Coen D.A., additional, van der Kallen, Carla J.H., additional, Schalkwijk, Casper G., additional, Wijmenga, Cisca, additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje F., additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, van Heemst, Diana, additional, Veldink, Jan H., additional, van den Berg, Leonard H., additional, van Duijn, Cornelia M., additional, Hofman, Bert A., additional, Uitterlinden, André G., additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H. Eka D., additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, Mei, Hailiang, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Dasha V., additional, Hof, Peter van ’t, additional, Deelen, Patrick, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, Bonder, Marc Jan, additional, van Dijk, Freerk, additional, Arindrarto, Wibowo, additional, Kielbasa, Szymon M., additional, Swertz, Morris A., additional, van Zwet, Erik. W., additional, and Hoen, Peter-Bram ’t, additional

Published
2019
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33. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

Author

Tobi, Elmar W., Slieker, Roderick C., Luijk, René, Dekkers, Koen F., Stein, Aryeh D., Xu, Kate M., Slagboom, P.E., Van Zwet, Erik W., Lumey, L.H., Heijmans, Bastiaan T., T'Hoen, Peter A., Pool, René, Van Greevenbroek, Marleen M., Stehouwer, Coen D., Van Der Kallen, Carla J., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan H., Van Den Berg, Leonard H., Van Duijn, Cornelia M., Hofman, Albert, Uitterlinden, André G., Jhamai, P.M., Verbiest, Michael, Verkerk, Marijn, Van Der Breggen, Ruud, Van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, Bot, Jan, Zhernakova, Dasha V., Van 't Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Jan Bonder, Marc, Van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., Isaacs, Aaron, Franke, Lude, Epidemiology and Data Science, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, Laboratory Medicine, RS-Theme Biopsychology of Learning, and Department FEEEL

Subjects
0301 basic medicine, BLOOD, Physiology, Genome-wide association study, Diseases and Disorders, Body Mass Index, 0302 clinical medicine, Pregnancy, Risk Factors, Medicine, MATERNAL SMOKING, EPIGENETIC REGULATION, Research Articles, 2. Zero hunger, Multidisciplinary, SciAdv r-articles, Middle Aged, DATA RESOURCE, EPIGENETIC EPIDEMIOLOGY, Metabolism disorder, 030220 oncology & carcinogenesis, Prenatal Exposure Delayed Effects, DNA methylation, Female, TXNIP, Research Article, Adult, FAMINE EXPOSURE, IN-UTERO, HUNGER WINTER FAMILIES, 03 medical and health sciences, BMI, AGE, SDG 3 - Good Health and Well-being, Metabolic Diseases, DUTCH FAMINE, Life Science, Humans, Epigenetics, EXPOSURE, Triglycerides, EPIGENOME-WIDE ASSOCIATION, Global Nutrition, Wereldvoeding, business.industry, dNaM, Human Genetics, DNA Methylation, medicine.disease, GENE, BODY-MASS INDEX, 030104 developmental biology, Starvation, business, Body mass index, Genome-Wide Association Study
Abstract

DNA methylation mediates the association of prenatal famine exposure with higher adult BMI and serum triglyceride levels., Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis. DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing β cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-term metabolic health. The specific mechanism awaits elucidation.

Published
2018

34. A SNP panel for identification of DNA and RNA specimens

Author

Yousefi, Soheil, Abbassi-Daloii, Tooba, Kraaijenbrink, Thirsa, Vermaat, Martijn, Mei, Hailiang, van't Hof, Peter, van Iterson, Maarten, Zhernakova, Daria V., Claringbould, Annique, Franke, Lude, 't Hart, Leen M., Slieker, Roderick C., van der Heijden, Amber, de Knijff, Peter, 't Hoen, Peter A. C., Jansen, R., van Meurs, J., Heijmans, B.T., Boomsma, D.I., van Dongen, J., Hottenga, Jouke-Jan, Slagboom, P.E., Suchiman, H. Eka D., van Zwet, Erik W., 't Hoen, P., Pool, R., van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, C., Zhernakova, A., Tigchelaar, E.F., Beekman, M, Deelen, J, van Heemst, D., Veldink, J H., van den Berg, L.H., van Duijn, C.M., Hofman, B. A., Uitterlinden, A. G., Jhamai, P. Mila, Verbiest, M., Verkerk, M., van der Breggen, Ruud, van Rooij, J., Lakenberg, N., Mei, H., Bot, J., Zhernakova, D. V., Van't Hof, P., Deelen, P., Nooren, I., Moed, M., Vermaat, M., Bonder, M.J., van Dijk, F., van Galen, M., Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., Isaacs, A., Franke, L., Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology and Data Science, APH - Aging & Later Life, General practice, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Interne Geneeskunde, MUMC+: HVC Pieken Maastricht Studie (9), and MUMC+: MA Interne Geneeskunde (3)

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), BLOOD, INDIVIDUAL IDENTIFICATION, Individuality, Linkage Disequilibrium, 0302 clinical medicine, Gene Frequency, MARKERS, Genotype, Ethnicity, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Mix up samples, Genetics, education.field_of_study, CODIS CORE LOCI, High-Throughput Nucleotide Sequencing, 16. Peace & justice, Justice and Strong Institutions, DNA profiling, POPULATIONS, DNA microarray, MESSENGER-RNA, Biotechnology, Research Article, Biobanking, Patient Identification Systems, SDG 16 - Peace, lcsh:QH426-470, lcsh:Biotechnology, Population, UNITED-STATES, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, VALIDATION, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, lcsh:TP248.13-248.65, Journal Article, SNP, Humans, 030216 legal & forensic medicine, Genetic Testing, Genetic variation, education, Genotyping, Forensics, SDG 16 - Peace, Justice and Strong Institutions, DNA, DNA Fingerprinting, Minor allele frequency, FORENSIC IDENTIFICATION, lcsh:Genetics, 030104 developmental biology, Genetics, Population, RNA, MULTIPLEX, Sample tracking, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Abstract

Background SNP panels that uniquely identify an individual are useful for genetic and forensic research. Previously recommended SNP panels are based on DNA profiles and mostly contain intragenic SNPs. With the increasing interest in RNA expression profiles, we aimed for establishing a SNP panel for both DNA and RNA-based genotyping. Results To determine a small set of SNPs with maximally discriminative power, genotype calls were obtained from DNA and blood-derived RNA sequencing data belonging to healthy, geographically dispersed, Dutch individuals. SNPs were selected based on different criteria like genotype call rate, minor allele frequency, Hardy–Weinberg equilibrium and linkage disequilibrium. A panel of 50 SNPs was sufficient to identify an individual uniquely: the probability of identity was 6.9 × 10− 20 when assuming no family relations and 1.2 × 10− 10 when accounting for the presence of full sibs. The ability of the SNP panel to uniquely identify individuals on DNA and RNA level was validated in an independent population dataset. The panel is applicable to individuals from European descent, with slightly lower power in non-Europeans. Whereas most of the genes containing the 50 SNPs are expressed in various tissues, our SNP panel needs optimization for other tissues than blood. Conclusions This first DNA/RNA SNP panel will be useful to identify sample mix-ups in biomedical research and for assigning DNA and RNA stains in crime scenes to unique individuals. Electronic supplementary material The online version of this article (10.1186/s12864-018-4482-7) contains supplementary material, which is available to authorized users.

Published
2018

35. Whole Transcriptome RNA Sequencing As a Comprehensive Diagnostic Tool for Acute Myeloid Leukemia

Author

Griffioen, Marieke, primary, Arindrarto, Wibowo, additional, Borras, Daniel M., additional, Locher, Irene J., additional, van Diessen, Saskia A.M.E., additional, van der Holst, Rosalie, additional, van der Meijden, Edith D., additional, Honders, M. Willy, additional, de Leeuw, Rick H., additional, Jedema, Inge, additional, Kroes, Wilma G.M., additional, Knijnenburg, Jeroen, additional, Vermaat, Joost, additional, Valk, Peter, additional, Janssen, Bart, additional, de Knijff, Peter, additional, van Bergen, Cornelis A.M., additional, van den Akker, Erik B., additional, 't Hoen, Peter A.C., additional, Kielbasa, Szymon M., additional, Laros, Jeroen F.J., additional, and Veelken, Hendrik, additional

Published
2018
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36. The Effect of Corticosteroids on Human Choroidal Endothelial Cells: A Model to Study Central Serous Chorioretinopathy

Author

Brinks, Joost, primary, van Dijk, Elon H. C., additional, Habeeb, Mahmoud, additional, Nikolaou, Aikaterini, additional, Tsonaka, Roula, additional, Peters, Hendrika A. B., additional, Sips, Hetty C. M., additional, van de Merbel, Arjanneke F., additional, de Jong, Eiko K., additional, Notenboom, Robbert G. E., additional, Kielbasa, Szymon M., additional, van der Maarel, Silvère M., additional, Quax, Paul H. A., additional, Meijer, Onno C., additional, and Boon, Camiel J. F., additional

Published
2018
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37. Primary Cutaneous Follicle Center Lymphomas (PCFCL) Express Heavily Mutated B-Cell Receptors with Acquired N-Glycosylation Motifs and Lack Ongoing Somatic Hypermutation

Author

Koning, Marvyn T., primary, Quinten, Edwin, additional, Zoutman, Willem H., additional, van der Zeeuw, Sander A.J., additional, Kielbasa, Szymon M., additional, Mei, Hailang, additional, van Bergen, Cornelis A.M., additional, Jansen, Patty M., additional, Willemze, Rein, additional, Schmidt, Christian, additional, Vermeer, Maarten, additional, Tensen, Cornelis P., additional, and Veelken, Hendrik, additional

Published
2018
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38. Selective glucocorticoid receptor modulation prevents and reverses non-alcoholic fatty liver disease in male mice

Author

Koorneef, Lisa L, primary, van den Heuvel, José K, additional, Kroon, Jan, additional, Boon, Mariëtte R, additional, ’t Hoen, Peter A C, additional, Hettne, Kristina M, additional, van de Velde, Nienke M, additional, Kolenbrander, Kelsey B, additional, Streefland, Trea C M, additional, Mol, Isabel M, additional, Sips, Hetty C M, additional, Kielbasa, Szymon M, additional, Mei, Hailiang, additional, Belanoff, Joseph K, additional, Pereira, Alberto M, additional, Oosterveer, Maaike H, additional, Hunt, Hazel, additional, Rensen, Patrick C N, additional, and Meijer, Onno C, additional

Published
2018
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39. Measuring similarities between transcription factor binding sites

Author

Gonze Didier, Kielbasa Szymon M, and Herzel Hanspeter

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Collections of transcription factor binding profiles (Transfac, Jaspar) are essential to identify regulatory elements in DNA sequences. Subsets of highly similar profiles complicate large scale analysis of transcription factor binding sites. Results We propose to identify and group similar profiles using two independent similarity measures: χ2 distances between position frequency matrices (PFMs) and correlation coefficients between position weight matrices (PWMs) scores. Conclusion We show that these measures complement each other and allow to associate Jaspar and Transfac matrices. Clusters of highly similar matrices are identified and can be used to optimise the search for regulatory elements. Moreover, the application of the measures is illustrated by assigning E-box matrices of a SELEX experiment and of experimentally characterised binding sites of circadian clock genes to the Myc-Max cluster.

Published
2005
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40. Disease variants alter transcription factor levels and methylation of their binding sites

Author

Bonder, Marc Jan, Luijk, René, Zhernakova, Daria V, Moed, Matthijs, Deelen, Patrick, Vermaat, Martijn, van Iterson, Maarten, van Dijk, Freerk, van Galen, Michiel, Bot, Jan, Slieker, Roderick C, Jhamai, P Mila, Verbiest, Michael, Suchiman, H Eka D, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Arindrarto, Wibowo, Kielbasa, Szymon M, Jonkers, Iris, van 't Hof, Peter, Nooren, Irene, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Zhernakova, Alexandra, Tigchelaar, Ettje F, Swertz, Morris A, Hofman, Albert, Uitterlinden, André G, Pool, René, van Dongen, Jenny, Hottenga, Jouke J, Stehouwer, Coen D A, van der Kallen, Carla J H, Schalkwijk, Casper G, van den Berg, Leonard H, van Zwet, Erik W, Mei, Hailiang, Li, Yang, Lemire, Mathieu, Hudson, Thomas J, Slagboom, P Eline, Wijmenga, Cisca, Veldink, Jan H, van Greevenbroek, Marleen M J, van Duijn, Cornelia M, Boomsma, Dorret I, Isaacs, Aaron, and BIOS Consortium

Subjects
Journal Article
Abstract

Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. Here we show that disease-associated variants have widespread effects on DNA methylation in trans that likely reflect differential occupancy of trans binding sites by cis-regulated transcription factors. Using multiple omics data sets from 3,841 Dutch individuals, we identified 1,907 established trait-associated SNPs that affect the methylation levels of 10,141 different CpG sites in trans (false discovery rate (FDR) < 0.05). These included SNPs that affect both the expression of a nearby transcription factor (such as NFKB1, CTCF and NKX2-3) and methylation of its respective binding site across the genome. Trans methylation QTLs effectively expose the downstream effects of disease-associated variants.

Published
2017

43. Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing

Author

Arindrarto, Wibowo, Borràs, Daniel M., de Groen, Ruben A. L., van den Berg, Redmar R., Locher, Irene J., van Diessen, Saskia A. M. E., van der Holst, Rosalie, van der Meijden, Edith D., Honders, M. Willy, de Leeuw, Rick H., Verlaat, Wina, Jedema, Inge, Kroes, Wilma G. M., Knijnenburg, Jeroen, van Wezel, Tom, Vermaat, Joost S. P., Valk, Peter J. M., Janssen, Bart, de Knijff, Peter, van Bergen, Cornelis A. M., van den Akker, Erik B., Hoen, Peter A. C. ’t, Kielbasa, Szymon M., Laros, Jeroen F. J., Griffioen, Marieke, and Veelken, Hendrik

Abstract

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics. We developed HAMLET (Human AML Expedited Transcriptomics) as bioinformatics pipeline for simultaneous detection of fusion genes, small variants, tandem duplications, and gene expression with all information assembled in an annotated, user-friendly output file. Whole transcriptome RNA sequencing was performed on 100 AML cases and HAMLET results were validated by reference assays and targeted resequencing. The data showed that HAMLET accurately detected all fusion genes and overexpression of EVI1irrespective of 3q26 aberrations. In addition, small variants in 13 genes that are often mutated in AML were called with 99.2% sensitivity and 100% specificity, and tandem duplications in FLT3and KMT2Awere detected by a novel algorithm based on soft-clipped reads with 100% sensitivity and 97.1% specificity. In conclusion, HAMLET has the potential to provide accurate comprehensive diagnostic information relevant for AML classification, risk assessment and targeted therapy on a single technology platform.

Published
2021
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44. Quaking Promotes Monocyte Differentiation Into Pro-Atherogenic Macrophages By Controlling Pre-Mrna Splicing And Gene Expression

Author

de Bruin, Ruben G., Shiue, Lily, Prins, Jurrien, de Boer, Hetty C., Singh, Anjana, Fagg, W. Samuel, van Gils, Janine M., Duijs, Jacques M. G. J., Katzman, Sol, Kraaijeveld, Adriaan O., Bohringer, Stefan, Leung, Wai Y., Kielbasa, Szymon M., Donahue, John P., van der Zande, Patrick H. J., Sijbom, Rick, van Alem, Carla M. A., Bot, Ilze, van Kooten, Cees, and Jukema, J. Wouter

Abstract

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.

Published
2016

45. Identification of context-dependent expression quantitative trait loci in whole blood

Author

Zhernakova, Daria V, primary, Deelen, Patrick, additional, Vermaat, Martijn, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Arindrarto, Wibowo, additional, van 't Hof, Peter, additional, Mei, Hailiang, additional, van Dijk, Freerk, additional, Westra, Harm-Jan, additional, Bonder, Marc Jan, additional, van Rooij, Jeroen, additional, Verkerk, Marijn, additional, Jhamai, P Mila, additional, Moed, Matthijs, additional, Kielbasa, Szymon M, additional, Bot, Jan, additional, Nooren, Irene, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke J, additional, Stehouwer, Coen D A, additional, van der Kallen, Carla J H, additional, Schalkwijk, Casper G, additional, Zhernakova, Alexandra, additional, Li, Yang, additional, Tigchelaar, Ettje F, additional, de Klein, Niek, additional, Beekman, Marian, additional, Deelen, Joris, additional, van Heemst, Diana, additional, van den Berg, Leonard H, additional, Hofman, Albert, additional, Uitterlinden, André G, additional, van Greevenbroek, Marleen M J, additional, Veldink, Jan H, additional, Boomsma, Dorret I, additional, van Duijn, Cornelia M, additional, Wijmenga, Cisca, additional, Slagboom, P Eline, additional, Swertz, Morris A, additional, Isaacs, Aaron, additional, van Meurs, Joyce B J, additional, Jansen, Rick, additional, Heijmans, Bastiaan T, additional, 't Hoen, Peter A C, additional, and Franke, Lude, additional

Published
2016
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46. Primary Mediastinal Large B-Cell Lymphoma Exhibits Autonomous BCR Signaling and Responds to the Second Generation BTK Inhibitor Acalabrutinib

Author

Koning, Marvyn T., primary, Übelhart, Rudolf, additional, van der Zeeuw, Sander A.J., additional, Kluin, Philip, additional, Griffioen, Marieke, additional, Drexler, Hans G., additional, Kielbasa, Szymon M., additional, Navarrete, Marcelo A., additional, Jumaa, Hassan, additional, and Veelken, Hendrik, additional

Published
2016
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47. Antigen-Independent, Autonomous B-Cell Receptor Signaling As a Dominant Candidate Oncogenic Mechanism in ABC DLBCL

Author

Koning, Marvyn T., primary, Übelhart, Rudolf, additional, Cleven, Arjen H.G., additional, Zoutman, Willem H., additional, van der Zeeuw, Sander A.J., additional, Kluin, Philip, additional, Griffioen, Marieke, additional, Tensen, Cornelis P., additional, Vermeer, Maarten H., additional, Willemze, Rein, additional, Kielbasa, Szymon M., additional, Navarrete, Marcelo A., additional, Jumaa, Hassan, additional, and Veelken, Hendrik, additional

Published
2016
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48. New function of the myostatin/activin type I receptor (ALK4) as a mediator of muscle atrophy and muscle regeneration

Author

Pasteuning‐Vuhman, Svitlana, primary, Boertje‐van der Meulen, Johanna W., additional, Putten, Maaike Van, additional, Overzier, Maurice, additional, Dijke, Peter, additional, Kielbasa, Szymon M., additional, Arindrarto, Wibowo, additional, Wolterbeek, Ron, additional, Lezhnina, Ksenia V., additional, Ozerov, Ivan V., additional, Aliper, Aleksandr M., additional, Hoogaars, Willem M., additional, Aartsma‐Rus, Annemieke, additional, and Loomans, Cindy J. M., additional

Published
2016
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49. Integrated Whole Genome and Transcriptome Analysis Identified a Therapeutic Minor Histocompatibility Antigen in a Splice Variant of ITGB2

Author

Pont, Margot J., primary, van der Lee, Dyantha I., additional, van der Meijden, Edith D., additional, van Bergen, Cornelis A.M., additional, Kester, Michel G.D., additional, Honders, Maria W., additional, Vermaat, Martijn, additional, Eefting, Matthias, additional, Marijt, Erik W.A., additional, Kielbasa, Szymon M., additional, Hoen, Peter A.C. 't, additional, Falkenburg, J.H. Frederik, additional, and Griffioen, Marieke, additional

Published
2016
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50. Abstract LB-012: Autonomous, antigen-independent B-cell receptor signalling as a novel pathogenetic mechanism in non-GCB DLBCL

Author

Koning, Marvyn T., primary, Übelhart, Rudolf, additional, Cleven, Arjen H.G., additional, Zoutman, Willem H., additional, van der Zeeuw, Sander A.J., additional, Kluin, Philip, additional, Griffioen, Marieke, additional, Drexler, Hans G., additional, Tensen, Cornelis P., additional, Vermeer, Maarten H., additional, Willemze, Rein, additional, Kielbasa, Szymon M., additional, Navarrete, Marcelo A., additional, Jumaa, Hassan, additional, and Veelken, Hendrik, additional

Published
2016
Full Text
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