Search

Your search keyword '"Bonder, Marc Jan"' showing total 338 results
Start Over Author "Bonder, Marc Jan"
338 results on '"Bonder, Marc Jan"'

3. Assembly of 43 human Y chromosomes reveals extensive complexity and variation

Author

Hallast, Pille, Ebert, Peter, Loftus, Mark, Yilmaz, Feyza, Audano, Peter A., Logsdon, Glennis A., Bonder, Marc Jan, Zhou, Weichen, Höps, Wolfram, Kim, Kwondo, Li, Chong, Hoyt, Savannah J., Dishuck, Philip C., Porubsky, David, Tsetsos, Fotios, Kwon, Jee Young, Zhu, Qihui, Munson, Katherine M., Hasenfeld, Patrick, Harvey, William T., Lewis, Alexandra P., Kordosky, Jennifer, Hoekzema, Kendra, O’Neill, Rachel J., Korbel, Jan O., Tyler-Smith, Chris, Eichler, Evan E., Shi, Xinghua, Beck, Christine R., Marschall, Tobias, Konkel, Miriam K., and Lee, Charles

Published
2023
Full Text
View/download PDF

6. Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics.

Author

Bonder, Marc Jan, Smail, Craig, Gloudemans, Michael J, Frésard, Laure, Jakubosky, David, D'Antonio, Matteo, Li, Xin, Ferraro, Nicole M, Carcamo-Orive, Ivan, Mirauta, Bogdan, Seaton, Daniel D, Cai, Na, Vakili, Dara, Horta, Danilo, Zhao, Chunli, Zastrow, Diane B, Bonner, Devon E, HipSci Consortium, iPSCORE consortium, Undiagnosed Diseases Network, PhLiPS consortium, Wheeler, Matthew T, Kilpinen, Helena, Knowles, Joshua W, Smith, Erin N, Frazer, Kelly A, Montgomery, Stephen B, and Stegle, Oliver

Subjects
HipSci Consortium, iPSCORE consortium, Undiagnosed Diseases Network, PhLiPS consortium, Cell Line, Humans, Bardet-Biedl Syndrome, Cerebellar Ataxia, Rare Diseases, Proteins, Calcium Channels, Sequence Analysis, RNA, DNA Methylation, Gene Expression, Regulatory Sequences, Nucleic Acid, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genetic Variation, Induced Pluripotent Stem Cells, Whole Genome Sequencing, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Human Genome, Stem Cell Research - Embryonic - Human, Regenerative Medicine, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human, Stem Cell Research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Generic health relevance, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases.

Published
2021

7. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author

Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I, Raygoza Garay, Juan Antonio, Finnicum, Casey T, Liu, Xingrong, Zhernakova, Daria V, Bonder, Marc Jan, Hansen, Tue H, Frost, Fabian, Rühlemann, Malte C, Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A, Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D, Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T, Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I, Burk, Robert D, Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E, van Duijn, Cornelia M, Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A, Ijzerman, Richard G, Jackson, Matthew A, Jaddoe, Vincent WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, Moll, Henriette A, Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J, Steves, Claire J, Thorsen, Jonathan, Timpson, Nicholas J, Tito, Raul Y, Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H, Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U, Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, Meyer, Katie A, Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C, Spector, Tim D, Uitterlinden, Andre G, Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M, Franke, Lude, Sanna, Serena, D’Amato, Mauro, and Pedersen, Oluf

Subjects
Microbiology, Biological Sciences, Genetics, Human Genome, Biotechnology, Clinical Research, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adolescent, Adult, Bifidobacterium, Child, Child, Preschool, Cohort Studies, Female, Gastrointestinal Microbiome, Genetic Variation, Genome-Wide Association Study, Humans, Lactase, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Metabolism, Quantitative Trait Loci, RNA, Ribosomal, 16S, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P

Published
2021

8. Properties of structural variants and short tandem repeats associated with gene expression and complex traits.

Author

Jakubosky, David, D'Antonio, Matteo, Bonder, Marc Jan, Smail, Craig, Donovan, Margaret KR, Young Greenwald, William W, Matsui, Hiroko, i2QTL Consortium, D'Antonio-Chronowska, Agnieszka, Stegle, Oliver, Smith, Erin N, Montgomery, Stephen B, DeBoever, Christopher, and Frazer, Kelly A

Subjects
i2QTL Consortium, Cell Line, Humans, Microsatellite Repeats, Multifactorial Inheritance, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genetic Variation, Genome-Wide Association Study, Genetics, Human Genome, Generic health relevance
Abstract

Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we identify genomic features of SV classes and STRs that are associated with gene expression and complex traits, including their locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We identify a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and show that they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that are associated with gene expression and human traits.

Published
2020

9. Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease.

Author

D'Antonio, Matteo, Reyna, Joaquin, Jakubosky, David, Donovan, Margaret Kr, Bonder, Marc-Jan, Matsui, Hiroko, Stegle, Oliver, Nariai, Naoki, D'Antonio-Chronowska, Agnieszka, and Frazer, Kelly A

Subjects
Humans, Cystic Fibrosis, Genetic Predisposition to Disease, HLA Antigens, Chromosome Mapping, Major Histocompatibility Complex, Haplotypes, Polymorphism, Single Nucleotide, Alleles, Quantitative Trait Loci, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, RNA-Seq, HLA types, computational biology, eQTLs, gene expression, genetics, genomics, human, major histocompatibility complex, systems biology, Biochemistry and Cell Biology
Abstract

The MHC region is highly associated with autoimmune and infectious diseases. Here we conduct an in-depth interrogation of associations between genetic variation, gene expression and disease. We create a comprehensive map of regulatory variation in the MHC region using WGS from 419 individuals to call eight-digit HLA types and RNA-seq data from matched iPSCs. Building on this regulatory map, we explored GWAS signals for 4083 traits, detecting colocalization for 180 disease loci with eQTLs. We show that eQTL analyses taking HLA type haplotypes into account have substantially greater power compared with only using single variants. We examined the association between the 8.1 ancestral haplotype and delayed colonization in Cystic Fibrosis, postulating that downregulation of RNF5 expression is the likely causal mechanism. Our study provides insights into the genetic architecture of the MHC region and pinpoints disease associations that are due to differential expression of HLA genes and non-HLA genes.

Published
2019

11. Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses

Author

Rodríguez-Ubreva, Javier, Arutyunyan, Anna, Bonder, Marc Jan, Del Pino-Molina, Lucía, Clark, Stephen J., de la Calle-Fabregat, Carlos, Garcia-Alonso, Luz, Handfield, Louis-François, Ciudad, Laura, Andrés-León, Eduardo, Krueger, Felix, Català-Moll, Francesc, Rodríguez-Cortez, Virginia C., Polanski, Krzysztof, Mamanova, Lira, van Dongen, Stijn, Kiselev, Vladimir Yu., Martínez-Saavedra, María T., Heyn, Holger, Martín, Javier, Warnatz, Klaus, López-Granados, Eduardo, Rodríguez-Gallego, Carlos, Stegle, Oliver, Kelsey, Gavin, Vento-Tormo, Roser, and Ballestar, Esteban

Published
2022
Full Text
View/download PDF

12. 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

14. ONCO-FETAL REPROGRAMMING DRIVES HIGH-RISK JUVENILE MYELOMONOCYTIC LEUKEMIA, WHICH CAN BE TARGETED BY ANTI-CD52 TREATMENT

Author

Hartmann, Mark, primary, Schönung, Maximilian, additional, Rajak, Jovana, additional, Hey, Joschka, additional, Maurer, Valentin, additional, Hai, Ling, additional, Staeble, Sina, additional, Langstein, Jens, additional, Bauer, Katharina, additional, Hakobyan, Mariam, additional, Jardine, Laura, additional, Bohler, Sheila, additional, Vonficht, Dominik, additional, Maag, Abdul-Habib, additional, Lebrecht, Dirk, additional, Bernt, Katrin M., additional, Roelz, Roland, additional, Boch, Tobias, additional, Khabirova, Eleonora, additional, Lutsik, Pavlo, additional, Haas, Simon, additional, Haniffa, Muzlifah, additional, Behjati, Sam, additional, Mallm, Jan-Philipp, additional, Buske, Christian, additional, Milsom, Michael D., additional, Fröhling, Stefan, additional, Bonder, Marc-Jan, additional, Niemeyer, Charlotte, additional, Flotho, Christian, additional, Plass, Christoph, additional, Erlacher, Miriam, additional, Schlesner, Matthias, additional, and Lipka, Daniel B., additional

Published
2023
Full Text
View/download PDF

15. Oncogenic RAS-Pathway Activation Drives Oncofetal Reprogramming and Creates Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia

Author

Hartmann, Mark, primary, Schoenung, Maximilian, additional, Rajak, Jovana, additional, Maurer, Valentin, additional, Hai, Ling, additional, Bauer, Katharina, additional, Hakobyan, Mariam, additional, Staeble, Sina, additional, Langstein, Jens, additional, Jardine, Laura, additional, Roelz, Roland, additional, Bohler, Sheila, additional, Khabirova, Eleonora, additional, Maag, Abdul-Habib, additional, Vonficht, Dominik, additional, Lebrecht, Dirk, additional, Bernt, Katrin M., additional, Tan, Kai, additional, Chen, Changya, additional, Alikarami, Fatemeh, additional, Boch, Tobias, additional, Flore, Viktoria, additional, Lutsik, Pavlo, additional, Milsom, Michael D., additional, Raffel, Simon, additional, Buske, Christian, additional, Haas, Simon, additional, Haniffa, Muzlifah, additional, Mallm, Jan-Philipp, additional, Behjati, Sam, additional, Bonder, Marc-Jan, additional, Froehling, Stefan, additional, Niemeyer, Charlotte M., additional, Hey, Joschka, additional, Flotho, Christian, additional, Plass, Christoph, additional, Erlacher, Miriam, additional, Schlesner, Matthias, additional, and Lipka, Daniel B., additional

Published
2023
Full Text
View/download PDF

16. 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
Full Text
View/download PDF

17. Expression profiling of cerebrospinal fluid identifies dysregulated antiviral mechanisms in multiple sclerosis.

Author

Ban, Maria, Bredikhin, Danila, Huang, Yuanhua, Bonder, Marc Jan, Katarzyna, Kania, Oliver, Amanda J, Wilson, Nicola K, Coupland, Paul, Hadfield, James, Göttgens, Berthold, Madissoon, Elo, Stegle, Oliver, and Sawcer, Stephen

Subjects
GENE expression, MULTIPLE sclerosis, CEREBROSPINAL fluid, LOCUS (Genetics), AUTOIMMUNE diseases, RNA splicing
Abstract

Despite the overwhelming evidence that multiple sclerosis is an autoimmune disease, relatively little is known about the precise nature of the immune dysregulation underlying the development of the disease. Reasoning that the CSF from patients might be enriched for cells relevant in pathogenesis, we have completed a high-resolution single-cell analysis of 96 732 CSF cells collected from 33 patients with multiple sclerosis (n = 48 675) and 48 patients with other neurological diseases (n = 48 057). Completing comprehensive cell type annotation, we identified a rare population of CD8+ T cells, characterized by the upregulation of inhibitory receptors, increased in patients with multiple sclerosis. Applying a Multi-Omics Factor Analysis to these single-cell data further revealed that activity in pathways responsible for controlling inflammatory and type 1 interferon responses are altered in multiple sclerosis in both T cells and myeloid cells. We also undertook a systematic search for expression quantitative trait loci in the CSF cells. Of particular interest were two expression quantitative trait loci in CD8+ T cells that were fine mapped to multiple sclerosis susceptibility variants in the viral control genes ZC3HAV1 (rs10271373) and IFITM2 (rs1059091). Further analysis suggests that these associations likely reflect genetic effects on RNA splicing and cell-type specific gene expression respectively. Collectively, our study suggests that alterations in viral control mechanisms might be important in the development of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

18. S206: ONCO-FETAL REPROGRAMMING DRIVES HIGH-RISK JUVENILE MYELOMONOCYTIC LEUKEMIA, WHICH CAN BE TARGETED BY ANTI-CD52 TREATMENT

Author

Hartmann, Mark, primary, Schönung, Maximilian, additional, Rajak, Jovana, additional, Hey, Joschka, additional, Maurer, Valentin, additional, Hai, Ling, additional, Staeble, Sina, additional, Langstein, Jens, additional, Bauer, Katharina, additional, Hakobyan, Mariam, additional, Jardine, Laura, additional, Bohler, Sheila, additional, Vonficht, Dominik, additional, Maag, Abdul-Habib, additional, Lebrecht, Dirk, additional, Bernt, Kathrin, additional, Rölz, Roland, additional, Boch, Tobias, additional, Khabirova, Eleonora, additional, Lutsik, Pavlo, additional, Haas, Simon, additional, Haniffa, Muzlifah, additional, Behjati, Sam, additional, Mallm, Jan-Philipp, additional, Buske, Christian, additional, Milsom, Michael, additional, Fröhling, Stefan, additional, Bonder, Marc-Jan, additional, Plass, Christoph, additional, Niemeyer, Charlotte, additional, Flotho, Christian, additional, Erlacher, Miriam, additional, Schlesner, Matthias, additional, and Lipka, Daniel B., additional

Published
2023
Full Text
View/download PDF

19. 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
Full Text
View/download PDF

21. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA.

Author

Fehrmann, Rudolf SN, Jansen, Ritsert C, Veldink, Jan H, Westra, Harm-Jan, Arends, Danny, Bonder, Marc Jan, Fu, Jingyuan, Deelen, Patrick, Groen, Harry JM, Smolonska, Asia, Weersma, Rinse K, Hofstra, Robert MW, Buurman, Wim A, Rensen, Sander, Wolfs, Marcel GM, Platteel, Mathieu, Zhernakova, Alexandra, Elbers, Clara C, Festen, Eleanora M, Trynka, Gosia, Hofker, Marten H, Saris, Christiaan GJ, Ophoff, Roel A, van den Berg, Leonard H, van Heel, David A, Wijmenga, Cisca, Te Meerman, Gerard J, and Franke, Lude

Subjects
Monocytes, Humans, HLA Antigens, Chromosome Mapping, Gene Expression Profiling, Gene Expression Regulation, Genotype, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genetic Variation, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these variants cause these phenotypes. Knowledge of these intermediate steps is crucial to understand pathogenesis, while also providing leads for potential pharmacological intervention. Here we relied upon natural human genetic variation to identify effects of these variants on trans-gene expression (expression quantitative trait locus mapping, eQTL) in whole peripheral blood from 1,469 unrelated individuals. We looked at 1,167 published trait- or disease-associated SNPs and observed trans-eQTL effects on 113 different genes, of which we replicated 46 in monocytes of 1,490 different individuals and 18 in a smaller dataset that comprised subcutaneous adipose, visceral adipose, liver tissue, and muscle tissue. HLA single-nucleotide polymorphisms (SNPs) were 10-fold enriched for trans-eQTLs: 48% of the trans-acting SNPs map within the HLA, including ulcerative colitis susceptibility variants that affect plausible candidate genes AOAH and TRBV18 in trans. We identified 18 pairs of unlinked SNPs associated with the same phenotype and affecting expression of the same trans-gene (21 times more than expected, P

Published
2011

22. OC 34 - ONCO-FETAL REPROGRAMMING DRIVES HIGH-RISK JUVENILE MYELOMONOCYTIC LEUKEMIA, WHICH CAN BE TARGETED BY ANTI-CD52 TREATMENT

Author

Hartmann, Mark, Schönung, Maximilian, Rajak, Jovana, Hey, Joschka, Maurer, Valentin, Hai, Ling, Staeble, Sina, Langstein, Jens, Bauer, Katharina, Hakobyan, Mariam, Jardine, Laura, Bohler, Sheila, Vonficht, Dominik, Maag, Abdul-Habib, Lebrecht, Dirk, Bernt, Katrin M., Roelz, Roland, Boch, Tobias, Khabirova, Eleonora, Lutsik, Pavlo, Haas, Simon, Haniffa, Muzlifah, Behjati, Sam, Mallm, Jan-Philipp, Buske, Christian, Milsom, Michael D., Fröhling, Stefan, Bonder, Marc-Jan, Niemeyer, Charlotte, Flotho, Christian, Plass, Christoph, Erlacher, Miriam, Schlesner, Matthias, and Lipka, Daniel B.

Published
2023
Full Text
View/download PDF

23. Single cell DNA methylation ageing in mouse blood

Author

Bonder, Marc Jan, primary, Clark, Stephen, additional, Krueger, Felix, additional, Luo, Siyuan, additional, Agostinho de Sousa, Joao, additional, Hashtroud, Aida M, additional, Stubbs, Thomas M, additional, Stark, Anne-Katrien, additional, Rulands, Steffen, additional, Stegle, Oliver, additional, Reik, Wolf, additional, and von Meyenn, Ferdinand, additional

Published
2023
Full Text
View/download PDF

24. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

Author

Zhernakova, Alexandra, Kurilshikov, Alexander, Bonder, Marc Jan, Tigchelaar, Ettje F., Schirmer, Melanie, Vatanen, Tommi, Mujagic, Zlatan, Vila, Arnau Vich, Falony, Gwen, Vieira-Silva, Sara, Wang, Jun, Imhann, Floris, Brandsma, Eelke, Jankipersadsing, Soesma A., Joossens, Marie, Cenit, Maria Carmen, Deelen, Patrick, Swertz, Morris A., study, LifeLines cohort, Weersma, Rinse K., Feskens, Edith J. M., Netea, Mihai G., Gevers, Dirk, Jonkers, Daisy, Franke, Lude, Aulchenko, Yurii S., Huttenhower, Curtis, Raes, Jeroen, Hofker, Marten H., Xavier, Ramnik J., Wijmenga, Cisca, and Fu, Jingyuan

Published
2016

25. Population-level analysis of gut microbiome variation

Author

Falony, Gwen, Joossens, Marie, Vieira-Silva, Sara, Wang, Jun, Darzi, Youssef, Faust, Karoline, Kurilshikov, Alexander, Bonder, Marc Jan, Valles-Colomer, Mireia, Vandeputte, Doris, Tito, Raul Y., Chaffron, Samuel, Rymenans, Leen, Verspecht, Chloë, De Sutter, Lise, Lima-Mendez, Gipsi, D'hoe, Kevin, Jonckheere, Karl, Homola, Daniel, Garcia, Roberto, Tigchelaar, Ettje F., Eeckhaudt, Linda, Fu, Jingyuan, Henckaerts, Liesbet, Zhernakova, Alexandra, Wijmenga, Cisca, and Raes, Jeroen

Published
2016

28. Multi-Omics Profiling of JMML HSPCs Reveals Onco-Fetal Reprogramming and Identifies Novel Prognostic Biomarkers and Therapeutic Targets in High-Risk JMML

Author

Hartmann, Mark, primary, Hai, Ling, additional, Hey, Joschka, additional, Schönung, Maximilian, additional, Maurer, Valentin, additional, Rajak, Jovana, additional, Staeble, Sina, additional, Langstein, Jens, additional, Bauer, Katharina, additional, Hakobyan, Mariam, additional, Jardine, Laura, additional, Bohler, Sheila, additional, Vonficht, Dominik, additional, Maag, Abdul-Habib, additional, Lebrecht, Dirk, additional, Bernt, Kathrin M., additional, Roelz, Roland, additional, Boch, Tobias, additional, Khabirova, Eleonora, additional, Lutsik, Pavlo, additional, Stegle, Oliver, additional, Haas, Simon, additional, Haniffa, Muzlifah, additional, Behjati, Sam, additional, Mallm, Jan-Philipp, additional, Buske, Christian, additional, Fröhling, Stefan, additional, Plass, Christoph, additional, Niemeyer, Charlotte M., additional, Flotho, Christian, additional, Bonder, Marc Jan, additional, Erlacher, Miriam, additional, Schlesner, Matthias, additional, and Lipka, Daniel B., additional

Published
2022
Full Text
View/download PDF

31. The effect of host genetics on the gut microbiome

Author

Bonder, Marc Jan, Kurilshikov, Alexander, Tigchelaar, Ettje F, Mujagic, Zlatan, Imhann, Floris, Vila, Arnau Vich, Deelen, Patrick, Vatanen, Tommi, Schirmer, Melanie, Smeekens, Sanne P, Zhernakova, Daria V, Jankipersadsing, Soesma A, Jaeger, Martin, Oosting, Marije, Cenit, Maria Carmen, Masclee, Ad A M, Swertz, Morris A, Li, Yang, Kumar, Vinod, Joosten, Leo, Harmsen, Hermie, Weersma, Rinse K, Franke, Lude, Hofker, Marten H, Xavier, Ramnik J, Jonkers, Daisy, Netea, Mihai G, Wijmenga, Cisca, Fu, Jingyuan, and Zhernakova, Alexandra

Published
2016
Full Text
View/download PDF

32. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease

Author

Imhann, Floris, Vich Vila, Arnau, Bonder, Marc Jan, Fu, Jingyuan, Gevers, Dirk, Visschedijk, Marijn C, Spekhorst, Lieke M, Alberts, Rudi, Franke, Lude, van Dullemen, Hendrik M, Ter Steege, Rinze W F, Huttenhower, Curtis, Dijkstra, Gerard, Xavier, Ramnik J, Festen, Eleonora A M, Wijmenga, Cisca, Zhernakova, Alexandra, and Weersma, Rinse K

Published
2018
Full Text
View/download PDF

33. Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative

Author

Wang, Jun, Kurilshikov, Alexander, Radjabzadeh, Djawad, Turpin, Williams, Croitoru, Kenneth, Bonder, Marc Jan, Jackson, Matthew A., Medina-Gomez, Carolina, Frost, Fabian, Homuth, Georg, Rühlemann, Malte, Hughes, David, Kim, Han-na, MiBioGen Consortium Initiative, Spector, Tim D., Bell, Jordana T., Steves, Claire J., Timpson, Nicolas, Franke, Andre, Wijmenga, Cisca, Meyer, Katie, Kacprowski, Tim, Franke, Lude, Paterson, Andrew D., Raes, Jeroen, Kraaij, Robert, and Zhernakova, Alexandra

Published
2018
Full Text
View/download PDF

34. DNA methylation signatures of educational attainment

Author

van Dongen, Jenny, Bonder, Marc Jan, Dekkers, Koen F., Nivard, Michel G., van Iterson, Maarten, Willemsen, Gonneke, Beekman, Marian, van der Spek, Ashley, van Meurs, Joyce B. J., Franke, Lude, Heijmans, Bastiaan T., van Duijn, Cornelia M., Slagboom, P. Eline, Boomsma, Dorret I., and BIOS consortium

Published
2018
Full Text
View/download PDF

35. 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., van Eijk, Kristel R., Moisse, Matthieu, Baird, Denis, Al Khleifat, Ahmad, Iacoangeli, Alfredo, 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, de 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, Wray, Naomi R., McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Tsai, Ellen, Runz, Heiko, Al-Chalabi, Ammar, van den Berg, Leonard H., Van Damme, Philip, Mill, Jonathan, Veldink, Jan H., Heijmans, Bastiaan T., t Hoen, Peter A.C., van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret I., Pool, René, 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., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, Eka H.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, 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., Bensimon, Gilbert, Smith, George Davey, 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., van Eijk, Kristel R., Moisse, Matthieu, Baird, Denis, Al Khleifat, Ahmad, Iacoangeli, Alfredo, 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, de 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, Wray, Naomi R., McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Tsai, Ellen, Runz, Heiko, Al-Chalabi, Ammar, van den Berg, Leonard H., Van Damme, Philip, Mill, Jonathan, Veldink, Jan H., Heijmans, Bastiaan T., t Hoen, Peter A.C., van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret I., Pool, René, 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., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, Eka H.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, 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., Bensimon, Gilbert, and Smith, George Davey

Abstract

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.

Published
2022
Full Text
View/download PDF

36. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity

Author

Wahl, Simone, Drong, Alexander, Lehne, Benjamin, Loh, Marie, Scott, William R., Kunze, Sonja, Tsai, Pei-Chien, Ried, Janina S., Zhang, Weihua, Yang, Youwen, Tan, Sili, Fiorito, Giovanni, Franke, Lude, Guarrera, Simonetta, Kasela, Silva, Kriebel, Jennifer, Richmond, Rebecca C., Adamo, Marco, Afzal, Uzma, Ala-Korpela, Mika, Albetti, Benedetta, Ammerpohl, Ole, Apperley, Jane F., Beekman, Marian, Bertazzi, Pier Alberto, Black, Lucas S., Blancher, Christine, Bonder, Marc-Jan, Brosch, Mario, Carstensen-Kirberg, Maren, de Craen, Anton J. M., de Lusignan, Simon, Dehghan, Abbas, Elkalaawy, Mohamed, Fischer, Krista, Franco, Oscar H., Gaunt, Tom R., Hampe, Jochen, Hashemi, Majid, Isaacs, Aaron, Jenkinson, Andrew, Jha, Sujeet, Kato, Norihiro, Krogh, Vittorio, Laffan, Michael, Meisinger, Christa, Meitinger, Thomas, Mok, Zuan Yu, Motta, Valeria, Ng, Hong Kiat, Nikolakopoulou, Zacharoula, Nteliopoulos, Georgios, Panico, Salvatore, Pervjakova, Natalia, Prokisch, Holger, Rathmann, Wolfgang, Roden, Michael, Rota, Federica, Rozario, Michelle Ann, Sandling, Johanna K., Schafmayer, Clemens, Schramm, Katharina, Siebert, Reiner, Slagboom, Eline P., Soininen, Pasi, Stolk, Lisette, Strauch, Konstantin, Tai, E-Shyong, Tarantini, Letizia, Thorand, Barbara, Tigchelaar, Ettje F., Tumino, Rosario, Uitterlinden, Andre G., van Duijn, Cornelia, van Meurs, Joyce B. J., Vineis, Paolo, Wickremasinghe, Ananda Rajitha, Wijmenga, Cisca, Yang, Tsun-Po, Yuan, Wei, Zhernakova, Alexandra, Batterham, Rachel L., Smith, George Davey, Deloukas, Panos, Heijmans, Bastiaan T., Herder, Christian, Hofman, Albert, Lindgren, Cecilia M., Milani, Lili, van der Harst, Pim, Peters, Annette, Illig, Thomas, Relton, Caroline L., Waldenberger, Melanie, Jürvelin, Marjo-Riitta, Bollati, Valentina, Soong, Richie, Spector, Tim D., Scott, James, McCarthy, Mark I., Elliott, Paul, Bell, Jordana T., Matullo, Giuseppe, Gieger, Christian, Kooner, Jaspal S., Grallert, Harald, and Chambers, John C.

Published
2017
Full Text
View/download PDF

39. Single-Cell Atlas of Common Variable Immunodeficiency reveals germinal center-associated epigenetic dysregulation in B cell responses

Author

Rodriguez-Ubreva, Javier, primary, Arutyunyan, Anna, additional, Bonder, Marc Jan, additional, Del Pino-Molina, Lucia, additional, Clark, Stephen, additional, de la Calle-Fabregat, Carlos, additional, Garcia-Alonso, Luz, additional, Handfield, Louis-Francois, additional, Ciudad, Laura, additional, Andres-Leon, Eduardo, additional, Krueger, Felix, additional, Catala-Moll, Francesc, additional, Rodriguez-Cortez, Virginia C, additional, Polanski, Krzysztof, additional, Mamanova, Lira, additional, van Dongen, Stijn, additional, Kiselev, Vladimir Yu, additional, Martinez-Saavedra, Maria T, additional, Heyn, Holger, additional, Martin, Javier, additional, Warnatz, Klaus, additional, Lopez-Granados, Eduardo, additional, Rodriguez-Gallego, Carlos, additional, Stegle, Oliver, additional, Kelsey, Gavin D, additional, Vento-Tormo, Roser, additional, and Ballestar, Esteban, additional

Published
2021
Full Text
View/download PDF

40. MICROBIOME: Population-level analysis of gut microbiome variation

Author

Falony, Gwen, Joossens, Marie, Vieira-Silva, Sara, Wang, Jun, Darzi, Youssef, Faust, Karoline, Kurilshikov, Alexander, Bonder, Marc Jan, Valles-Colomer, Mireia, Vandeputte, Doris, Tito, Raul Y., Chaffron, Samuel, Rymenans, Leen, Verspecht, Chloë, De Sutter, Lise, Lima-Mendez, Gipsi, Dʼhoe, Kevin, Jonckheere, Karl, Homola, Daniel, Garcia, Roberto, Tigchelaar, Ettje F., Eeckhaudt, Linda, Fu, Jingyuan, Henckaerts, Liesbet, Zhernakova, Alexandra, Wijmenga, Cisca, and Raes, Jeroen

Published
2016
Full Text
View/download PDF

41. MICROBIOME: Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

Author

Zhernakova, Alexandra, Kurilshikov, Alexander, Bonder, Marc Jan, Tigchelaar, Ettje F., Schirmer, Melanie, Vatanen, Tommi, Mujagic, Zlatan, Vila, Arnau Vich, Falony, Gwen, Vieira-Silva, Sara, Wang, Jun, Imhann, Floris, Brandsma, Eelke, Jankipersadsing, Soesma A., Joossens, Marie, Cenit, Maria Carmen, Deelen, Patrick, Swertz, Morris A., Weersma, Rinse K., Feskens, Edith J. M., Netea, Mihai G., Gevers, Dirk, Jonkers, Daisy, Franke, Lude, Aulchenko, Yurii S., Huttenhower, Curtis, Raes, Jeroen, Hofker, Marten H., Xavier, Ramnik J., Wijmenga, Cisca, and Fu, Jingyuan

Published
2016

42. Population-scale proteome variation in human induced pluripotent stem cells

Author

Mirauta, Bogdan Andrei, Seaton, Daniel D, Bensaddek, Dalila, Brenes, Alejandro, Bonder, Marc Jan, Kilpinen, Helena, Agu, Chukwuma A, Alderton, Alex, Danecek, Petr, Denton, Rachel, Durbin, Richard, Gaffney, Daniel J, Goncalves, Angela, Halai, Reena, Harper, Sarah, Kirton, Christopher M, Kolb-Kokocinski, Anja, Leha, Andreas, McCarthy, Shane A, Memari, Yasin, Patel, Minal, Birney, Ewan, Casale, Francesco Paolo, Clarke, Laura, Harrison, Peter W, Streeter, Ian, Denovi, Davide, Stegle, Oliver, Lamond, Angus I, Meleckyte, Ruta, Moens, Natalie, Watt, Fiona M, Ouwehand, Willem H, Beales, Philip, Mirauta, Bogdan Andrei [0000-0002-9733-292X], Bonder, Marc Jan [0000-0002-8431-3180], Kilpinen, Helena [0000-0001-6692-6154], Stegle, Oliver [0000-0002-8818-7193], Lamond, Angus I [0000-0001-6204-6045], Apollo - University of Cambridge Repository, and Helsinki Institute of Life Science HiLIFE

Subjects
Male, Proteomics, Proteome, Genome-wide association study, VARIANTS, Transcriptome, 0302 clinical medicine, SCHIZOPHRENIA, Human proteome project, genetics, Disease, Biology (General), Induced pluripotent stem cell, Child, GENE-EXPRESSION, 0303 health sciences, education.field_of_study, Drug discovery, General Neuroscience, General Medicine, Middle Aged, Phenotype, Child, Preschool, Medicine, ABUNDANCE, Female, Research Article, Adult, Adolescent, Genotype, QH301-705.5, induced pluripotent stem cells, Science, Population, Quantitative Trait Loci, deleterious variants, Genomics, Computational biology, Quantitative trait locus, Biology, General Biochemistry, Genetics and Molecular Biology, DIFFERENTIAL EXPRESSION, 03 medical and health sciences, Young Adult, RESOURCE, REVEALS, genomics, Humans, human, RNA, Messenger, education, 030304 developmental biology, Aged, IDENTIFICATION, General Immunology and Microbiology, Infant, Newborn, Genetic Variation, Infant, Genetics and Genomics, QUANTIFICATION, Genetics, Population, REGULATORY VARIATION, 3111 Biomedicine, 030217 neurology & neurosurgery
Abstract

Human disease phenotypes are driven primarily by alterations in protein expression and/or function. To date, relatively little is known about the variability of the human proteome in populations and how this relates to variability in mRNA expression and to disease loci. Here, we present the first comprehensive proteomic analysis of human induced pluripotent stem cells (iPSC), a key cell type for disease modelling, analysing 202 iPSC lines derived from 151 donors, with integrated transcriptome and genomic sequence data from the same lines. We characterised the major genetic and non-genetic determinants of proteome variation across iPSC lines and assessed key regulatory mechanisms affecting variation in protein abundance. We identified 654 protein quantitative trait loci (pQTLs) in iPSCs, including disease-linked variants in protein-coding sequences and variants with trans regulatory effects. These include pQTL linked to GWAS variants that cannot be detected at the mRNA level, highlighting the utility of dissecting pQTL at peptide level resolution.

Published
2020

43. Optimising expression quantitative trait locus mapping workflows for single-cell studies (Supplementary information)

Author

Cuomo, Anna and Bonder, Marc Jan

Abstract

Supplementary data linked to the: "Optimising expression quantitative trait locus mapping workflows for single-cell studies" manuscript. Both the expression matrices of the matching bulk and single cell data and metadata, and the checked out software used in the project.(The bulk data is normalized, the single cell data are raw counts.)&nbsp

Published
2021
Full Text
View/download PDF

47. Haplotype-resolved diverse human genomes and integrated analysis of structural variation

Author

Ebert, Peter, primary, Audano, Peter A., additional, Zhu, Qihui, additional, Rodriguez-Martin, Bernardo, additional, Porubsky, David, additional, Bonder, Marc Jan, additional, Sulovari, Arvis, additional, Ebler, Jana, additional, Zhou, Weichen, additional, Serra Mari, Rebecca, additional, Yilmaz, Feyza, additional, Zhao, Xuefang, additional, Hsieh, PingHsun, additional, Lee, Joyce, additional, Kumar, Sushant, additional, Lin, Jiadong, additional, Rausch, Tobias, additional, Chen, Yu, additional, Ren, Jingwen, additional, Santamarina, Martin, additional, Höps, Wolfram, additional, Ashraf, Hufsah, additional, Chuang, Nelson T., additional, Yang, Xiaofei, additional, Munson, Katherine M., additional, Lewis, Alexandra P., additional, Fairley, Susan, additional, Tallon, Luke J., additional, Clarke, Wayne E., additional, Basile, Anna O., additional, Byrska-Bishop, Marta, additional, Corvelo, André, additional, Evani, Uday S., additional, Lu, Tsung-Yu, additional, Chaisson, Mark J. P., additional, Chen, Junjie, additional, Li, Chong, additional, Brand, Harrison, additional, Wenger, Aaron M., additional, Ghareghani, Maryam, additional, Harvey, William T., additional, Raeder, Benjamin, additional, Hasenfeld, Patrick, additional, Regier, Allison A., additional, Abel, Haley J., additional, Hall, Ira M., additional, Flicek, Paul, additional, Stegle, Oliver, additional, Gerstein, Mark B., additional, Tubio, Jose M. C., additional, Mu, Zepeng, additional, Li, Yang I., additional, Shi, Xinghua, additional, Hastie, Alex R., additional, Ye, Kai, additional, Chong, Zechen, additional, Sanders, Ashley D., additional, Zody, Michael C., additional, Talkowski, Michael E., additional, Mills, Ryan E., additional, Devine, Scott E., additional, Lee, Charles, additional, Korbel, Jan O., additional, Marschall, Tobias, additional, and Eichler, Evan E., additional

Published
2021
Full Text
View/download PDF

48. Additional file 3 of Combined single-cell profiling of expression and DNA methylation reveals splicing regulation and heterogeneity

Author

Linker, Stephanie M., Urban, Lara, Clark, Stephen J., Chhatriwala, Mariya, Shradha Amatya, McCarthy, Davis J., Ebersberger, Ingo, Vallier, Ludovic, Reik, Wolf, Stegle, Oliver, and Bonder, Marc Jan

Abstract

Supplementary Results & Figure S1-S11. Supplementary results on the deep modeling of the splicing states in single cells and the Figures S1 to S11. (PDF 2190 kb)

Published
2020
Full Text
View/download PDF

49. 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., Byrne, Enda M., Bartels, Meike, Wray, Naomi R., Middeldorp, Christel M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-guzman, 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, Penninx, Brenda, 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, P. Eline, Stehouwer, Coen D.a., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A.c., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, 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, Van Dongen, Jenny, Hottenga, Jouke J., Van Greevenbroek, Marleen Mj., 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, Van Galen, Michiel, Bot, Jan, Zhernakova, Daria V., Hof, Peter Van ‘t, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., Van Zwet, Erik. W., Hoen, Peter-bram ‘t, Hammerschlag, Anke R., Byrne, Enda M., Bartels, Meike, Wray, Naomi R., Middeldorp, Christel M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-guzman, 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, Penninx, Brenda, 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, P. Eline, Stehouwer, Coen D.a., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A.c., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, 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, Van Dongen, Jenny, Hottenga, Jouke J., Van Greevenbroek, Marleen Mj., 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, Van Galen, Michiel, Bot, Jan, Zhernakova, Daria V., Hof, Peter Van ‘t, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., Van Zwet, Erik. W., and Hoen, Peter-bram ‘t

Abstract

Background: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels. Methods: We applied summary-data–based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data–based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels. Results: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before. Conclusions: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies.

Published
2020
Full Text
View/download PDF

50. Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Sinha, Trishla, Vich Vila, Arnau, Garmaeva, Sanzhima, Jankipersadsing, Soesma A., Imhann, Floris, Collij, Valerie, Bonder, Marc Jan, Jiang, Xiaofang, Gurry, Thomas Jerome, Alm, Eric J, D’Amato, Mauro, Weersma, Rinse K., Scherjon, Sicco, Wijmenga, Cisca, Fu, Jingyuan, Kurilshikov, Alexander, Zhernakova, Alexandra, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Sinha, Trishla, Vich Vila, Arnau, Garmaeva, Sanzhima, Jankipersadsing, Soesma A., Imhann, Floris, Collij, Valerie, Bonder, Marc Jan, Jiang, Xiaofang, Gurry, Thomas Jerome, Alm, Eric J, D’Amato, Mauro, Weersma, Rinse K., Scherjon, Sicco, Wijmenga, Cisca, Fu, Jingyuan, Kurilshikov, Alexander, and Zhernakova, Alexandra

Abstract

Published with license by Taylor & Francis Group, LLC. Several gastrointestinal diseases show a sex imbalance, although the underlying (patho)physiological mechanisms behind this are not well understood. The gut microbiome may be involved in this process, forming a complex interaction with host immune system, sex hormones, medication and other environmental factors. Here we performed sex-specific analyses of fecal microbiota composition in 1135 individuals from a population-based cohort. The overall gut microbiome composition of females and males was significantly different (p = 0.001), with females showing a greater microbial diversity (p = 0.009). After correcting for the effects of intrinsic factors, smoking, diet and medications, female hormonal factors such as the use of oral contraceptives and undergoing an ovariectomy were associated with microbial species and pathways. Females had a higher richness of antibiotic-resistance genes, with the most notable being resistance to the lincosamide nucleotidyltransferase (LNU) gene family. The higher abundance of resistance genes is consistent with the greater prescription of the Macrolide-Lincosamide-Streptogramin classes of antibiotics to females. Furthermore, we observed an increased resistance to aminoglycosides in females with self-reported irritable bowel syndrome. These results throw light upon the effects of common medications that are differentially prescribed between sexes and highlight the importance of sex-specific analysis when studying the gut microbiome and resistome.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results