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38 results on '"de Klein, Niek"'

1. KidneyNetwork: using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease

Author

Boulogne, Floranne, Claus, Laura R., Wiersma, Henry, Oelen, Roy, Schukking, Floor, de Klein, Niek, Li, Shuang, Westra, Harm-Jan, van der Zwaag, Bert, van Reekum, Franka, Sierks, Dana, Schönauer, Ria, Li, Zhigui, Bijlsma, Emilia K., Bos, Willem Jan W., Halbritter, Jan, Knoers, Nine V. A. M., Besse, Whitney, Deelen, Patrick, Franke, Lude, and van Eerde, Albertien M.

Published
2023
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2. Misexpression of inactive genes in whole blood is associated with nearby rare structural variants

Author

Vanderstichele, Thomas, Burnham, Katie L., de Klein, Niek, Tardaguila, Manuel, Howell, Brittany, Walter, Klaudia, Kundu, Kousik, Koeppel, Jonas, Lee, Wanseon, Tokolyi, Alex, Persyn, Elodie, Nath, Artika P., Marten, Jonathan, Petrovski, Slavé, Roberts, David J., Di Angelantonio, Emanuele, Danesh, John, Berton, Alix, Platt, Adam, Butterworth, Adam S., Soranzo, Nicole, Parts, Leopold, Inouye, Michael, Paul, Dirk S., and Davenport, Emma E.

Published
2024
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3. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, Wouter, van der Spek, Rick AA, Bakker, Mark K, van Vugt, Joke JFA, Hop, Paul J, Zwamborn, Ramona AJ, de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B, Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M, Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs HP, van Eijk, Kristel R, Kooyman, Maarten, Byrne, Ross P, Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N, Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J, Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H, Bell, Shaughn, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S, Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A, Ross, Jay P, Ludolph, Albert C, Weishaupt, Jochen H, Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine AM, Saker-Delye, Safa, Wood, Nicholas W, Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, and Kraft, Julia

Subjects
Human Genome, Neurodegenerative, Clinical Research, Rare Diseases, Prevention, ALS, Neurosciences, Genetics, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Amyotrophic Lateral Sclerosis, Brain, Cholesterol, Disease Progression, Female, Genome-Wide Association Study, Glutamine, Humans, Male, Mendelian Randomization Analysis, Microsatellite Repeats, Mutation, Neurodegenerative Diseases, Neurons, Quantitative Trait Loci, RNA-Seq, Risk Factors, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, SLAP Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.

Published
2021

4. Brain expression quantitative trait locus and network analyses reveal downstream effects and putative drivers for brain-related diseases

Author

de Klein, Niek, Tsai, Ellen A., Vochteloo, Martijn, Baird, Denis, Huang, Yunfeng, Chen, Chia-Yen, van Dam, Sipko, Oelen, Roy, Deelen, Patrick, Bakker, Olivier B., El Garwany, Omar, Ouyang, Zhengyu, Marshall, Eric E., Zavodszky, Maria I., van Rheenen, Wouter, Bakker, Mark K., Veldink, Jan, Gaunt, Tom R., Runz, Heiko, Franke, Lude, and Westra, Harm-Jan

Published
2023
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5. Meta-analyses identify DNA methylation associated with kidney function and damage

Author

Schlosser, Pascal, Tin, Adrienne, Matias-Garcia, Pamela R., Thio, Chris H. L., Joehanes, Roby, Liu, Hongbo, Weihs, Antoine, Yu, Zhi, Hoppmann, Anselm, Grundner-Culemann, Franziska, Min, Josine L., Adeyemo, Adebowale A., Agyemang, Charles, Ärnlöv, Johan, Aziz, Nasir A., Baccarelli, Andrea, Bochud, Murielle, Brenner, Hermann, Breteler, Monique M. B., Carmeli, Cristian, Chaker, Layal, Chambers, John C., Cole, Shelley A., Coresh, Josef, Corre, Tanguy, Correa, Adolfo, Cox, Simon R., de Klein, Niek, Delgado, Graciela E., Domingo-Relloso, Arce, Eckardt, Kai-Uwe, Ekici, Arif B., Endlich, Karlhans, Evans, Kathryn L., Floyd, James S., Fornage, Myriam, Franke, Lude, Fraszczyk, Eliza, Gao, Xu, Gào, Xīn, Ghanbari, Mohsen, Ghasemi, Sahar, Gieger, Christian, Greenland, Philip, Grove, Megan L., Harris, Sarah E., Hemani, Gibran, Henneman, Peter, Herder, Christian, Horvath, Steve, Hou, Lifang, Hurme, Mikko A., Hwang, Shih-Jen, Jarvelin, Marjo-Riitta, Kardia, Sharon L. R., Kasela, Silva, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Kramer, Holly, Kronenberg, Florian, Kühnel, Brigitte, Lehtimäki, Terho, Lind, Lars, Liu, Dan, Liu, Yongmei, Lloyd-Jones, Donald M., Lohman, Kurt, Lorkowski, Stefan, Lu, Ake T., Marioni, Riccardo E., März, Winfried, McCartney, Daniel L., Meeks, Karlijn A. C., Milani, Lili, Mishra, Pashupati P., Nauck, Matthias, Navas-Acien, Ana, Nowak, Christoph, Peters, Annette, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ratliff, Scott M., Reiner, Alex P., Rosas, Sylvia E., Schöttker, Ben, Schwartz, Joel, Sedaghat, Sanaz, Smith, Jennifer A., Sotoodehnia, Nona, Stocker, Hannah R., Stringhini, Silvia, Sundström, Johan, Swenson, Brenton R., Tellez-Plaza, Maria, van Meurs, Joyce B. J., van Vliet-Ostaptchouk, Jana V., Venema, Andrea, Verweij, Niek, Walker, Rosie M., Wielscher, Matthias, Winkelmann, Juliane, Wolffenbuttel, Bruce H. R., Zhao, Wei, Zheng, Yinan, Loh, Marie, Snieder, Harold, Levy, Daniel, Waldenberger, Melanie, Susztak, Katalin, Köttgen, Anna, and Teumer, Alexander

Published
2021
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6. Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

Author

Karabegović, Irma, Portilla-Fernandez, Eliana, Li, Yang, Ma, Jiantao, Maas, Silvana C. E., Sun, Daokun, Hu, Emily A., Kühnel, Brigitte, Zhang, Yan, Ambatipudi, Srikant, Fiorito, Giovanni, Huang, Jian, Castillo-Fernandez, Juan E., Wiggins, Kerri L., de Klein, Niek, Grioni, Sara, Swenson, Brenton R., Polidoro, Silvia, Treur, Jorien L., Cuenin, Cyrille, Tsai, Pei-Chien, Costeira, Ricardo, Chajes, Veronique, Braun, Kim, Verweij, Niek, Kretschmer, Anja, Franke, Lude, van Meurs, Joyce B. J., Uitterlinden, André G., de Knegt, Robert J., Ikram, M. Arfan, Dehghan, Abbas, Peters, Annette, Schöttker, Ben, Gharib, Sina A., Sotoodehnia, Nona, Bell, Jordana T., Elliott, Paul, Vineis, Paolo, Relton, Caroline, Herceg, Zdenko, Brenner, Hermann, Waldenberger, Melanie, Rebholz, Casey M., Voortman, Trudy, Pan, Qiuwei, Fornage, Myriam, Levy, Daniel, Kayser, Manfred, and Ghanbari, Mohsen

Published
2021
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7. Potential impact of celiac disease genetic risk factors on T cell receptor signaling in gluten-specific CD4+ T cells

Author

Bakker, Olivier B., Ramírez-Sánchez, Aarón D., Borek, Zuzanna A., de Klein, Niek, Li, Yang, Modderman, Rutger, Kooy-Winkelaar, Yvonne, Johannesen, Marie K., Matarese, Filomena, Martens, Joost H. A., Kumar, Vinod, van Bergen, Jeroen, Qiao, Shuo-Wang, Lundin, Knut E. A., Sollid, Ludvig M., Koning, Frits, Wijmenga, Cisca, Withoff, Sebo, and Jonkers, Iris H.

Published
2021
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9. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Hübner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Jr., Robert H., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.

Published
2022
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12. Genetic regulation of gene expression in brain and blood

Author

de Klein, Niek, de Klein, Niek, de Klein, Niek, and de Klein, Niek

Abstract

Our genetic code is stored in our DNA, which consists of four bases: adenine (A), cytosine (C) guanine (G) and thymine (T). More than three billion of these bases are strung together in 23 chromosomes, forming our genome. Each of our cells has two copies of our genome, containing instructions that guide cellular processes such as growth, development, signalling, and many more, but can occasionally also be the basis of disease. A large part of the genetic instructions are contained in our genes, which are small regions in our genome which contain information to make ribonucleic acid molecules (RNA), which can be translated to proteins. Variation in our genomes can change the regulation of genes or the functionality of the protein products. The work in this thesis shows the effects of genetic variation on the activity (the amount of RNA that is produced) of genes. Often, the effect of genetic variation differs between tissues and cell types. We developed a method to study the difference in genetic regulation between different cell types and applied this to samples taken from brain and blood. We show that there are large differences in genetic regulation between brain and blood, and we identify putatively causal disease genes for several neuro-psychiatric disease which could not be identified using only data from blood. This thesis expanded our knowledge of the difference in genetic regulation of gene expression between brain and blood, which can help us in further understanding genetic diseases and in designing drug targets.

Published
2021

14. KidneyNetwork: Using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease

Author

Boulogne, Floranne, primary, Claus, Laura, additional, Wiersma, Henry, additional, Oelen, Roy, additional, Schukking, Floor, additional, de Klein, Niek, additional, Li, Shuang, additional, Westra, Harm-Jan, additional, Zwaag, Bert van der, additional, Reekum, Franka van, additional, Sierks, Dana, additional, Schönauer, Ria, additional, Li, Zhigui, additional, Bijlsma, Emilia, additional, Bos, Willem Jan, additional, Halbritter, Jan, additional, Knoers, Nine, additional, Besse, Whitney, additional, Deelen, Patrick, additional, Franke, Lude, additional, and Eerde, Albertien van, additional

Published
2022
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17. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, Wouter, van der Spek, Rick A A, Shireby, Gemma, Whiteman, David C, Olsen, Catherine M, Uitterlinden, Andre G, Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Consortium, SLALOM, Consortium, PARALS, Hannon, Eilis, Consortium, SLAGEN, Consortium, SLAP, Traynor, Bryan J, Singleton, Andrew B, Mitne Neto, Miguel, Cauchi, Ruben J, Ophoff, Roel A, Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M, Moisse, Matthieu, Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W, Steinbach, Robert, Baird, Denis, Hübner, Christian A, Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Restuadi, Restuadi, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P, Kiernan, Matthew C, Benyamin, Beben, Henderson, Robert D, Furlong, Sarah, Mathers, Susan, Dolzhenko, Egor, McCombe, Pamela A, Needham, Merrilee, Ngo, Shyuan T, Nicholson, Garth A, Pamphlett, Roger, Rowe, Dominic B, Steyn, Frederik J, Williams, Kelly L, Mather, Karen A, Sachdev, Perminder S, Dekker, Annelot M, Henders, Anjali K, Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A, Silani, Vincenzo, Curtis, Charles J, Breen, Gerome, Gawor, Klara, Glass, Jonathan D, Brown, Robert H, Landers, John E, Shaw, Christopher E, Andersen, Peter M, Groen, Ewout J N, van Es, Michael A, Pasterkamp, R Jeroen, Fan, Dongsheng, Garton, Fleur C, Westeneng, Henk-Jan, McRae, Allan F, Davey Smith, George, Gaunt, Tom R, Eberle, Michael A, Mill, Jonathan, McLaughlin, Russell L, Hardiman, Orla, Kenna, Kevin P, Wray, Naomi R, Tsai, Ellen, Tazelaar, Gijs H P, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H, Veldink, Jan H, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Bakker, Mark K, van Eijk, Kristel R, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Kooyman, Maarten, Bono, Giorgio, Canosa, Antonio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Byrne, Ross P, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, Doherty, Mark, De Marchi, Fabiola, Corrado, Lucia, D'Alfonso, Sandra, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, Heverin, Mark, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Al Khleifat, Ahmad, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Iacoangeli, Alfredo, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P, Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Shatunov, Aleksey, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L, Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Ticozzi, Nicola, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Cooper-Knock, Johnathan, van Vugt, Joke J F A, Smith, Bradley N, Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Sendtner, Michael, Meyer, Thomas, Hop, Paul J, Başak, Nazli, van der Kooi, Anneke J, Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, Zwamborn, Ramona A J, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Grassano, Maurizio, de Klein, Niek, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H, Westra, Harm-Jan, Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S, Assialioui, Abdelilah, Rojas-García, Ricardo, Bakker, Olivier B, Dion, Patrick A, Ross, Jay P, Ludolph, Albert, Weishaupt, Jochen H, Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Dürr, Alexandra, Payan, Christine A M, Deelen, Patrick, Saker-Delye, Safa, Wood, Nicholas W, Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, and Kraft, Julia

Subjects
ddc:570, Genetics, Medizin
Abstract

In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.

Published
2021
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18. FC 011KIDNEYNETWORK: USING KIDNEY DERIVED GENE EXPRESSION DATA TO PREDICT AND PRIORITIZE NOVEL GENES INVOLVED IN KIDNEY DISEASE

Author

Boulogne, Floranne, primary, Claus, Laura, additional, Wiersma, Henry, additional, Oelen, Roy, additional, Schukking, Floor, additional, De Klein, Niek, additional, Li, Shuang, additional, Westra, Harm-Jan, additional, Van der Zwaag, Bert, additional, Van Reekum, Franka, additional, Halbritter, Jan, additional, Knoers, Nine, additional, Research Consortium, Genomics England, additional, Deelen, Patrick, additional, Franke, Lude, additional, and Van Eerde, Albertien M, additional

Published
2021
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19. Common and rare variant association analyses in Amyotrophic Lateral Sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

Rheenen, Wouter van, primary, Spek, Rick van der, additional, Bakker, Mark, additional, Berg, Leonard van den, additional, Veldink, Jan, additional, Vugt, Joke van, additional, Hop, Paul, additional, Zwamborn, Ramona, additional, de Klein, Niek, additional, Westra, Harm-Jan, additional, Bakker, Olivier, additional, Deelen, Patrick, additional, Shireby, Gemma, additional, Hannon, Eilis, additional, Moisse, Matthieu, additional, Baird, Denis, additional, Restuadi, Restuadi, additional, Dolzhenko, Egor, additional, Dekker, Annelot, additional, Gawor, Klara, additional, Westeneng, Henk-Jan, additional, Tazelaar, Gijs, additional, Eijk, Kristel van, additional, Kooyman, Maarten, additional, Byrne, Ross, additional, Doherty, Mark, additional, Heverin, Mark, additional, Khleifat, Ahmad Al, additional, Iacoangeli, Alfredo, additional, Shatunov, Aleksey, additional, Ticozzi, Nicola, additional, Cooper-Knock, Johnathan, additional, Smith, Bradley, additional, Gromicho, Marta, additional, Chandran, Siddharthan, additional, Pal, Suvankar, additional, Morrison, Karen, additional, Shaw, Pamela, additional, Hardy, John, additional, Orrell, Richard, additional, Sendtner, Michael, additional, Meyer, Thomas, additional, Basak, Nazli, additional, Kooi, Anneke van der, additional, Ratti, Antonia, additional, Fogh, Isabella, additional, Gellera, Cinzia, additional, Pinter, Guiseppe Lauria, additional, Corti, Stefania, additional, Cereda, Cristina, additional, Sproviero, Daisy, additional, D'Alfonso, Sandra, additional, Soraru, Gianni, additional, Siciliano, Gabriele, additional, Filosto, Massimiliano, additional, Padovani, Alessandro, additional, Chio, Adriano, additional, Calvo, Andrea, additional, Moglia, Cristina, additional, Brunetti, Maura, additional, Canosa, Antonio, additional, Grassano, Maurizio, additional, Beghi, Ettore, additional, Pupillo, Elisabetta, additional, Logroscino, Giancarlo, additional, Nefussy, Beatrice, additional, Osmanovic, Alma, additional, Nordin, Angelica, additional, Lerner, Yossef, additional, Zabari, Michal, additional, Gotkine, Marc, additional, Baloh, Robert, additional, Bell, Shaugn, additional, Vourc'h, Patrick, additional, Corcia, Philippe, additional, Couratier, Philippe, additional, Millecamps, Stephanie, additional, Meininger, Vincent, additional, Salachas, Francois, additional, Pardina, Jesus Mora, additional, Assialioui, Abdelilah, additional, Rojas-García, Ricardo, additional, Dion, Patrick, additional, Ross, Jay, additional, Ludolph, Albert, additional, Weishaupt, Jochen, additional, Brenner, David, additional, Freischmidt, Axel, additional, Bensimon, Gilbert, additional, Brice, Alexis, additional, Durr, Alexandra, additional, Payan, Christine, additional, Saker-Delye, Safa, additional, Wood, Nicholas, additional, Topp, Simon, additional, Rademakers, Rosa, additional, Tittmann, Lukas, additional, Lieb, Wolfgang, additional, Franke, Andre, additional, Ripke, Stephan, additional, Braun, Alice, additional, Kraft, Julia, additional, Whiteman, David, additional, Olsen, Catherine, additional, Uitterlinden, André, additional, Hofman, Albert, additional, Rietschel, Marcella, additional, Cichon, Sven, additional, Nöthen, Markus, additional, Amouyel, Philippe, additional, Traynor, Bryan, additional, Singleton, Andrew, additional, Neto, Miguel Mitne, additional, Cauchi, Ruben, additional, Ophoff, Roel, additional, Wiedau-Pazos, Martina, additional, Lomen-Hoerth, Catherine, additional, Deerlin, Vivianna Van, additional, Grosskreutz, Julian, additional, Rödiger, Annekathrin, additional, Jörk, Alexander, additional, Barthel, Tabea, additional, Theele, Erik, additional, Ilse, Berjamin, additional, Stubendorff, Beatrice, additional, Witte, Otto, additional, Steinbach, Robert, additional, Hübner, Christian, additional, Graff, Caroline, additional, Brylev, Lev, additional, Fominykh, Vera, additional, Demeshonok, Vera, additional, Ataulina, Anastasia, additional, Rogelj, Boris, additional, Koritnik, Blaž, additional, Zidar, Janez, additional, Ravnik-Glavač, Metka, additional, Glavač, Damjan, additional, Stević, Zorica, additional, Drory, Vivian, additional, Povedano, Mónica, additional, Blair, Ian, additional, Kiernan, Matthew, additional, Benyamin, Beben, additional, Henderson, Robert, additional, Furlong, Sarah, additional, Mathers, Susan, additional, McCombe, Pamela, additional, Needham, Merrilee, additional, Ngo, Shyuan, additional, Nicholson, Garth, additional, Pamphlett, Roger, additional, Rowe, Dominic, additional, Steyn, Frederik, additional, Williams, Kelly, additional, Mather, Karen, additional, Sachdev, Perminder, additional, Henders, Anjali, additional, Wallace, Leanne, additional, de Carvalho, Mamede, additional, Pinto, Susana, additional, Petri, Susanne, additional, Weber, Markus, additional, Rouleau, Guy, additional, Silani, Vincenzo, additional, Curtis, Charles, additional, Breen, Gerome, additional, Glass, Jonathan, additional, Brown, Robert, additional, Landers, John, additional, Shaw, Christopher, additional, Andersen, Peter, additional, Groen, Ewout, additional, Es, Michael van, additional, Pasterkamp, Jeroen, additional, Fan, Dongsheng, additional, Garton, Fleur, additional, McRae, Allan, additional, Smith, George Davey, additional, Gaunt, Tom, additional, Eberle, Michael, additional, Mill, Jonathan, additional, McLaughlin, Russell, additional, Hardiman, Orla, additional, Kenna, Kevin, additional, Wray, Naomi, additional, Tsai, Ellen, additional, Runz, Heiko, additional, Franke, Lude, additional, Al-Chalabi, Ammar, additional, Damme, Philip Van, additional, and Gaur, Nayana, additional

Published
2021
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20. Brain expression quantitative trait locus and network analysis reveals downstream effects and putative drivers for brain-related diseases

Author

de Klein, Niek, primary, Tsai, Ellen A., additional, Vochteloo, Martijn, additional, Baird, Denis, additional, Huang, Yunfeng, additional, Chen, Chia-Yen, additional, van Dam, Sipko, additional, Deelen, Patrick, additional, Bakker, Olivier B., additional, Garwany, Omar El, additional, Ouyang, Zhengyu, additional, Marshall, Eric E., additional, Zavodszky, Maria I., additional, van Rheenen, Wouter, additional, Bakker, Mark K., additional, Veldink, Jan, additional, Gaunt, Tom R., additional, Runz, Heiko, additional, Franke, Lude, additional, and Westra, Harm-Jan, additional

Published
2021
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21. Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

Author

Karabegović, Irma, primary, Portilla-Fernandez, Eliana, additional, Li, Yang, additional, Ma, Jiantao, additional, Maas, Silvana C.E., additional, Sun, Daokun, additional, Hu, Emily A., additional, Kühnel, Brigitte, additional, Zhang, Yan, additional, Ambatipudi, Srikant, additional, Fiorito, Giovanni, additional, Huang, Jian, additional, Castillo-Fernandez, Juan E., additional, Wiggins, Kerri L., additional, de Klein, Niek, additional, Grioni, Sara, additional, Swenson, Brenton R., additional, Polidoro, Silvia, additional, Treur, Jorien L., additional, Cuenin, Cyrille, additional, Tsai, Pei-Chien, additional, Costeira, Ricardo, additional, Chajes, Veronique, additional, Braun, Kim, additional, Verweij, Niek, additional, Kretschmer, Anja, additional, Franke, Lude, additional, van Meurs, Joyce B.J., additional, Uitterlinden, André G., additional, de Knegt, Robert J., additional, Ikram, M. Arfan, additional, Dehghan, Abbas, additional, Peters, Annette, additional, Schöttker, Ben, additional, Gharib, Sina A., additional, Sotoodehnia, Nona, additional, Bell, Jordana T., additional, Elliott, Paul, additional, Vineis, Paolo, additional, Relton, Caroline, additional, Herceg, Zdenko, additional, Brenner, Hermann, additional, Waldenberger, Melanie, additional, Rebholz, Casey M., additional, Voortman, Trudy, additional, Pan, Qiuwei, additional, Fornage, Myriam, additional, Levy, Daniel, additional, Kayser, Manfred, additional, and Ghanbari, Mohsen, additional

Published
2020
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22. Deconvolution of bulk blood eQTL effects into immune cell subpopulations

Author

Aguirre-Gamboa, Raul, primary, de Klein, Niek, additional, Tommaso, Jennifer di, additional, Claringbould, Annique, additional, Wijst, Monique van der, additional, de Vries, Dylan, additional, Brugge, Harm, additional, Oelen, Roy, additional, Võsa, Urmo, additional, Zorro, Maria, additional, Chu, Xiaojin, additional, Bakker, Olivier B, additional, Borek, Zuzanna, additional, Ricaño-Ponce, Isis, additional, Deelen, Patrick, additional, Xu, Cheng-Jian, additional, Swertz, Morris, additional, Jonkers, Iris, additional, Withoff, Sebo, additional, Joosten, Irma, additional, Sanna, Serena, additional, Kumar, Vinod, additional, Koenen, Hans, additional, Joosten, Leo A.B., additional, Netea, Mihai, additional, Wijmenga, Cisca, additional, Franke, Lude, additional, and Li, Yang, additional

Published
2020
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23. Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults

Author

Parmar, Priyanka, Lowry, Estelle, Cugliari, Giovanni, Suderman, Matthew, Wilson, Rory, Karhunen, Ville, Andrew, Toby, Wiklund, Petri, Wielscher, Matthias, Guarrera, Simonetta, Teumer, Alexander, Lehne, Benjamin, Milani, Lili, de Klein, Niek, Mishra, Pashupati P., Melton, Phillip E., Mandaviya, Pooja R., Kasela, Silva, Nano, Jana, Zhang, Weihua, Zhang, Yan, Uitterlinden, Andre G., Peters, Annette, Schoettker, Ben, Gieger, Christian, Anderson, Denise, Boomsma, Dorret, I, Grabe, Hans J., Panico, Salvatore, Veldink, Jan H., van Meurs, Joyce B. J., van den Berg, Leonard, Beilin, Lawrence J., Franke, Lude, Loh, Marie, van Greevenbroek, Marleen M. J., Nauck, Matthias, Kahonen, Mika, Hurme, Mikko A., Raitakari, Olli T., Franco, Oscar H., Slagboom, P. Eline, van der Harst, Pim, Kunze, Sonja, Felix, Stephan B., Zhang, Tao, Chen, Wei, Mori, Trevor A., Bonnefond, Amelie, Heijmans, Bastiaan T., Muka, Taulant, Kooner, Jaspal S., Fischer, Krista, Waldenberger, Melanie, Froguel, Philippe, Huang, Rae-Chi, Lehtimaki, Terho, Rathmann, Wolfgang, Relton, Caroline L., Matullo, Giuseppe, Brenner, Hermann, Verweij, Niek, Li, Shengxu, Chambers, John C., Jarvelin, Marjo-Riitta, Sebert, Sylvain, Parmar, Priyanka, Lowry, Estelle, Cugliari, Giovanni, Suderman, Matthew, Wilson, Rory, Karhunen, Ville, Andrew, Toby, Wiklund, Petri, Wielscher, Matthias, Guarrera, Simonetta, Teumer, Alexander, Lehne, Benjamin, Milani, Lili, de Klein, Niek, Mishra, Pashupati P., Melton, Phillip E., Mandaviya, Pooja R., Kasela, Silva, Nano, Jana, Zhang, Weihua, Zhang, Yan, Uitterlinden, Andre G., Peters, Annette, Schoettker, Ben, Gieger, Christian, Anderson, Denise, Boomsma, Dorret, I, Grabe, Hans J., Panico, Salvatore, Veldink, Jan H., van Meurs, Joyce B. J., van den Berg, Leonard, Beilin, Lawrence J., Franke, Lude, Loh, Marie, van Greevenbroek, Marleen M. J., Nauck, Matthias, Kahonen, Mika, Hurme, Mikko A., Raitakari, Olli T., Franco, Oscar H., Slagboom, P. Eline, van der Harst, Pim, Kunze, Sonja, Felix, Stephan B., Zhang, Tao, Chen, Wei, Mori, Trevor A., Bonnefond, Amelie, Heijmans, Bastiaan T., Muka, Taulant, Kooner, Jaspal S., Fischer, Krista, Waldenberger, Melanie, Froguel, Philippe, Huang, Rae-Chi, Lehtimaki, Terho, Rathmann, Wolfgang, Relton, Caroline L., Matullo, Giuseppe, Brenner, Hermann, Verweij, Niek, Li, Shengxu, Chambers, John C., Jarvelin, Marjo-Riitta, and Sebert, Sylvain

Abstract

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under

Published
2018
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24. Deconvolution of bulk blood eQTL effects into immune cell subpopulations.

Author

Aguirre-Gamboa, Raúl, de Klein, Niek, di Tommaso, Jennifer, Claringbould, Annique, van der Wijst, Monique GP, de Vries, Dylan, Brugge, Harm, Oelen, Roy, Võsa, Urmo, Zorro, Maria M., Chu, Xiaojin, Bakker, Olivier B., Borek, Zuzanna, Ricaño-Ponce, Isis, Deelen, Patrick, Xu, Cheng-Jiang, Swertz, Morris, Jonkers, Iris, Withoff, Sebo, and Joosten, Irma

Subjects
*DECONVOLUTION (Mathematics), *BLOOD, *CELLS, *LOCUS (Genetics), *BLOOD sampling
Abstract

Background: Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL). Results: The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96–100%) and chromatin mark QTL (≥87–92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect. Conclusions: Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application (https://github.com/molgenis/systemsgenetics/tree/master/Decon2) and as a web tool (www.molgenis.org/deconvolution). [ABSTRACT FROM AUTHOR]

Published
2020
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25. Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

Author

Parmar, Priyanka, primary, Lowry, Estelle, additional, Cugliari, Giovanni, additional, Suderman, Matthew, additional, Wilson, Rory, additional, Karhunen, Ville, additional, Andrew, Toby, additional, Wiklund, Petri, additional, Wielscher, Matthias, additional, Guarrera, Simonetta, additional, Teumer, Alexander, additional, Lehne, Benjamin, additional, Milani, Lili, additional, de Klein, Niek, additional, Mishra, Pashupati P., additional, Melton, Phillip E., additional, Mandaviya, Pooja R., additional, Kasela, Silva, additional, Nano, Jana, additional, Zhang, Weihua, additional, Zhang, Yan, additional, Uitterlinden, Andre G., additional, Peters, Annette, additional, Schöttker, Ben, additional, Gieger, Christian, additional, Anderson, Denise, additional, Boomsma, Dorret I., additional, Grabe, Hans J., additional, Panico, Salvatore, additional, Veldink, Jan H., additional, van Meurs, Joyce B.J., additional, van den Berg, Leonard, additional, Beilin, Lawrence J., additional, Franke, Lude, additional, Loh, Marie, additional, van Greevenbroek, Marleen M.J., additional, Nauck, Matthias, additional, Kähönen, Mika, additional, Hurme, Mikko A., additional, Raitakari, Olli T., additional, Franco, Oscar H., additional, Slagboom, P.Eline, additional, van der Harst, Pim, additional, Kunze, Sonja, additional, Felix, Stephan B., additional, Zhang, Tao, additional, Chen, Wei, additional, Mori, Trevor A., additional, Bonnefond, Amelie, additional, Heijmans, Bastiaan T., additional, Muka, Taulant, additional, Kooner, Jaspal S., additional, Fischer, Krista, additional, Waldenberger, Melanie, additional, Froguel, Philippe, additional, Huang, Rae-Chi, additional, Lehtimäki, Terho, additional, Rathmann, Wolfgang, additional, Relton, Caroline L., additional, Matullo, Giuseppe, additional, Brenner, Hermann, additional, Verweij, Niek, additional, Li, Shengxu, additional, Chambers, John C., additional, Järvelin, Marjo-Riitta, additional, and Sebert, Sylvain, additional

Published
2018
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26. Meta-Analysis of Maternal Prenatal Smoking GFI1-Locus and Cardio-Metabolic Phenotypes in Adults

Author

Parmar, Priyanka, primary, Lowry, Estelle, additional, Cugliari, Giovanni, additional, Suderman, Matthew, additional, Wilson, Rory P., additional, Karhunen, Ville, additional, Andrew, Toby, additional, Wiklund, Petri, additional, Wielscher, Matthias, additional, Guarrera, Simonetta, additional, Teumer, Alexander, additional, Lehne, Benjamin, additional, Milani, Lili, additional, de Klein, Niek, additional, Mishra, Pashupati, additional, Melton, Phillip, additional, Mandaviya, Pooja R., additional, Kasela, Silva, additional, Nano, Jana, additional, Zhang, Weihua, additional, Zhang, Yan, additional, Uitterlinden, Andre G., additional, Peters, Annette, additional, Schöttker, Ben, additional, Gieger, Christian, additional, Anderson, Denise, additional, Boomsma, Dorret I., additional, Grabe, Hans J., additional, Veldink, Jan H., additional, van Meurs, Joyce B.J., additional, van den Berg, Leonard H., additional, Beilin, Lawrence J., additional, Franke, Lude, additional, Loh, Marie, additional, van Greevenbroek, Marleen M.J., additional, Nauck, Matthias, additional, Kähönen, Mika, additional, Hurme, Mikko A., additional, Raitakari, Olli, additional, Franco, Oscar H., additional, Slagboom, Eline, additional, van der Harst, Pim, additional, Kunze, Sonja, additional, Felix, Stephan B., additional, Zhang, Tao, additional, Chen, Wei, additional, Mori, Trevor A., additional, Bonnefond, Amelie, additional, Heijmans, B.T., additional, Muka, Taulant, additional, Kooner, Jaspal S., additional, Fischer, Krista, additional, Waldenberger, Melanie, additional, Froguel, Philippe, additional, Huang, Rae-Chi, additional, Lehtimäki, Terho, additional, Rathmann, Wolfgang, additional, Relton, Caroline L., additional, Matullo, Giuseppe, additional, Brenner, Hermann, additional, Verweij, Niek, additional, Li, Shengxu, additional, Chambers, John C., additional, Järvelin, Marjo-Riitta, additional, and Sébert, Sylvain P., additional

Published
2018
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27. Identification of context-dependent expression quantitative trait loci in whole blood

Author

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

Published
2017

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

Author

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

Abstract

Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology1,2. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations(3-6). Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease(7-17). Here we generated peripheral blood RNA-seq data from 2,116 unrelated individuals and systematically identified context-dependent eQTLs using a hypothesis-free strategy that does not require previous knowledge of the identity of the modifiers. Of the 23,060 significant cis-regulated genes (false discovery rate (FDR)

Published
2017

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

Author

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

Published
2017

30. TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation

Author

Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Mechanical Engineering, Massachusetts Institute of Technology. Department of Physics, Varma, Mukund Madhav, Guzman, Gaelen Donnelly, Schenone, Monica, Rivas, Manuel A, Daly, Mark J, Carr, Steven A, Xavier, Ramnik Joseph, Graham, Daniel B., Lefkovith, Ariel, Deelen, Patrick, de Klein, Niek, Boroughs, Angela, Desch, A. Nicole, Ng, Aylwin C.Y., Petersen, Christine P., Bhan, Atul K., Wijmenga, Cisca, Daly, Mark J., Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Mechanical Engineering, Massachusetts Institute of Technology. Department of Physics, Varma, Mukund Madhav, Guzman, Gaelen Donnelly, Schenone, Monica, Rivas, Manuel A, Daly, Mark J, Carr, Steven A, Xavier, Ramnik Joseph, Graham, Daniel B., Lefkovith, Ariel, Deelen, Patrick, de Klein, Niek, Boroughs, Angela, Desch, A. Nicole, Ng, Aylwin C.Y., Petersen, Christine P., Bhan, Atul K., Wijmenga, Cisca, and Daly, Mark J.

Abstract

Summary - Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5–61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis., Leona M. and Harry B. Helmsley Charitable Trust (2014PG-IBD016), Crohn's and Colitis Foundation of America, National Institutes of Health (U.S.) (grant DK043351), National Institutes of Health (U.S.) (grant DK097485)

Published
2017

31. Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

Author

Luxembourg’s National Research Fund (FNR), Swiss National Research Foundation (SNF) [sponsor], Rodius, Sophie, Androsova, Ganna, Götz, Lou, Liechti, Robin, Crespo, Isaac, Merz, Susanne, Nazarov, Petr, de Klein, Niek, Jeanty, Céline, González-Rosa, Juan, Muller, Arnaud, Bernardin, Francois, Niclou, Simone, Vallar, Laurent, Mercader, Nadia, Ibberson, Mark, Xenarios, Ioannis, Azuaje, Francisco, Luxembourg’s National Research Fund (FNR), Swiss National Research Foundation (SNF) [sponsor], Rodius, Sophie, Androsova, Ganna, Götz, Lou, Liechti, Robin, Crespo, Isaac, Merz, Susanne, Nazarov, Petr, de Klein, Niek, Jeanty, Céline, González-Rosa, Juan, Muller, Arnaud, Bernardin, Francois, Niclou, Simone, Vallar, Laurent, Mercader, Nadia, Ibberson, Mark, Xenarios, Ioannis, and Azuaje, Francisco

Abstract

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.

Published
2016

32. 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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33. TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation

Author

Graham, Daniel B., primary, Lefkovith, Ariel, additional, Deelen, Patrick, additional, de Klein, Niek, additional, Varma, Mukund, additional, Boroughs, Angela, additional, Desch, A. Nicole, additional, Ng, Aylwin C.Y., additional, Guzman, Gaelen, additional, Schenone, Monica, additional, Petersen, Christine P., additional, Bhan, Atul K., additional, Rivas, Manuel A., additional, Daly, Mark J., additional, Carr, Steven A., additional, Wijmenga, Cisca, additional, and Xavier, Ramnik J., additional

Published
2016
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35. A gene mapping bottleneck in the translational route from zebrafish to human.

Author

de Klein, Niek, Ibberson, Mark, Crespo, Isaac, Rodius, Sophie, Azuaje, Francisco, and Ponomarenko, Mikhail P.

Subjects
GENE mapping research, GENETIC techniques, GENETIC distance, ZEBRA danio, BRACHYDANIO
Abstract

Among a diversity of animal models of disease, the zebrafish is a promising model organism for enabling novel translational biomedical research. To fully achieve the latter, a key requirement is to match molecular readouts measured in zebrafish with information relevant to health and disease in humans. A fundamental step in this direction is to accurately map gene sequences from zebrafish to humans. Despite significant progress in genome annotation, this remains an intricate and time-consuming challenge. Here we discuss major obstacles that we had to overcome to systematically map genes from zebrafish to human. We identified important disparities, as well as partial agreements, between five public zebrafish-to-human homology resources. There is still a need for standardized, comprehensive genomic mappings between zebrafish and humans. Without this, efforts to use zebrafish as a powerful translational research tool will be stalled. [ABSTRACT FROM AUTHOR]

Published
2015
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36. Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

Author

Petri Wiklund, Melanie Waldenberger, Lili Milani, Wei Chen, André G. Uitterlinden, Hans J. Grabe, Pim van der Harst, Shengxu Li, Pashupati P. Mishra, John C. Chambers, Rae-Chi Huang, Jaspal S. Kooner, Giovanni Cugliari, Lawrence J. Beilin, Joyce B. J. van Meurs, Mika Kähönen, Rory P. Wilson, Phillip E. Melton, P. Eline Slagboom, Benjamin Lehne, Matthias Nauck, Simonetta Guarrera, Sylvain Sebert, Giuseppe Matullo, Matthias Wielscher, Weihua Zhang, Tao Zhang, Yan Zhang, Mikko Hurme, Niek de Klein, Hermann Brenner, Marjo-Riitta Järvelin, Krista Fischer, Annette Peters, Silva Kasela, Trevor A. Mori, Taulant Muka, Terho Lehtimäki, Oscar H. Franco, Leonard H. van den Berg, Pooja R. Mandaviya, Toby Andrew, Matthew Suderman, Marie Loh, Niek Verweij, Lude Franke, Ville Karhunen, Priyanka Parmar, Wolfgang Rathmann, Alexander Teumer, Jana Nano, Sonja Kunze, Estelle Lowry, Denise Anderson, Christian Gieger, Philippe Froguel, Dorret I. Boomsma, Jan H. Veldink, Marleen M.J. van Greevenbroek, Caroline L Relton, Salvatore Panico, Bastiaan T. Heijmans, Amélie Bonnefond, Stephan B. Felix, Olli T. Raitakari, Ben Schöttker, Maastricht Centre for Systems Biology, Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, RS: FSE MaCSBio, Internal Medicine, Epidemiology, Lee Kong Chian School of Medicine (LKCMedicine), Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Parmar, Priyanka, Lowry, Estelle, Cugliari, Giovanni, Suderman, Matthew, Wilson, Rory, Karhunen, Ville, Andrew, Toby, Wiklund, Petri, Wielscher, Matthia, Guarrera, Simonetta, Teumer, Alexander, Lehne, Benjamin, Milani, Lili, de Klein, Niek, Mishra, Pashupati P, Melton, Phillip E, Mandaviya, Pooja R, Kasela, Silva, Nano, Jana, Zhang, Weihua, Zhang, Yan, Uitterlinden, Andre G, Peters, Annette, Schöttker, Ben, Gieger, Christian, Anderson, Denise, Boomsma, Dorret I, Grabe, Hans J, Panico, Salvatore, Veldink, Jan H, van Meurs, Joyce B J, van den Berg, Leonard, Beilin, Lawrence J, Franke, Lude, Loh, Marie, van Greevenbroek, Marleen M J, Nauck, Matthia, Kähönen, Mika, Hurme, Mikko A, Raitakari, Olli T, Franco, Oscar H, Slagboom, P Eline, van der Harst, Pim, Kunze, Sonja, Schill, FELIX STEPHAN, Zhang, Tao, Chen, Wei, Mori, Trevor A, Bonnefond, Amelie, Heijmans, Bastiaan T, Muka, Taulant, Kooner, Jaspal S, Fischer, Krista, Waldenberger, Melanie, Froguel, Philippe, Huang, Rae-Chi, Lehtimäki, Terho, Rathmann, Wolfgang, Relton, Caroline L, Matullo, Giuseppe, Brenner, Hermann, Verweij, Niek, Li, Shengxu, Chambers, John C, Järvelin, Marjo-Riitta, Sebert, Sylvain, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
Genetics and Molecular Biology (all), Male, Netherlands Twin Register (NTR), 0301 basic medicine, Research paper, GFI1 protein, human, GFI1-locus, raskaus, Research & Experimental Medicine, cardio-metabolic phenotypes, Biochemistry, Epigenesis, Genetic, GLOBAL Meth QTL Consortium, 0302 clinical medicine, Pregnancy, Smoke, 030212 general & internal medicine, maternal prenatal smoking, DNA METHYLATION, media_common, RISK, 2. Zero hunger, education.field_of_study, Smoking, ta3142, General Medicine, Middle Aged, genetics [Transcription Factors], 3. Good health, DNA-Binding Proteins, Phenotype, Medicine, Research & Experimental, CARDIOVASCULAR-DISEASE, epigenetiikka, Population Surveillance, Prenatal Exposure Delayed Effects, DNA methylation, Female, Disease Susceptibility, BIOS Consortium, Medical Genetics, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Offspring, Birth weight, Population, Mothers, genetics [DNA-Binding Proteins], ta3111, Methylation, General Biochemistry, Genetics and Molecular Biology, DIET, 03 medical and health sciences, Medicine, General & Internal, SDG 3 - Good Health and Well-being, tupakointi, General & Internal Medicine, Internal medicine, medicine, media_common.cataloged_instance, Humans, ddc:610, adverse effects [Maternal Exposure], EXPOSURE, Epigenetics, European union, education, Medicinsk genetik, EPIGENOME-WIDE ASSOCIATION, Biochemistry, Genetics and Molecular Biology (all), Science & Technology, business.industry, adverse effects [Smoking], DNA Methylation, ta3121, medicine.disease, BIRTH-WEIGHT, 030104 developmental biology, Endocrinology, Genetic Loci, sydän- ja verisuonitaudit, CpG Islands, CIGARETTE-SMOKING, CESSATION, Energy Metabolism, metabolism [Myocardium], business, Body mass index, Biomarkers, Transcription Factors
Abstract

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health.Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP).Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH. (c) 2018 The Authors. Published by Elsevier B.V.

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

Author

Zhernakova DV, Deelen P, Vermaat M, van Iterson M, van Galen M, Arindrarto W, van 't Hof P, Mei H, van Dijk F, Westra HJ, Bonder MJ, van Rooij J, Verkerk M, Jhamai PM, Moed M, Kielbasa SM, Bot J, Nooren I, Pool R, van Dongen J, Hottenga JJ, Stehouwer CD, van der Kallen CJ, Schalkwijk CG, Zhernakova A, Li Y, Tigchelaar EF, de Klein N, Beekman M, Deelen J, van Heemst D, van den Berg LH, Hofman A, Uitterlinden AG, van Greevenbroek MM, Veldink JH, Boomsma DI, van Duijn CM, Wijmenga C, Slagboom PE, Swertz MA, Isaacs A, van Meurs JB, Jansen R, Heijmans BT, 't Hoen PA, and Franke L

Subjects
Cohort Studies, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, RNA, Messenger genetics, Blood Proteins genetics, Cell Lineage genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, RNA, Messenger blood, Regulatory Sequences, Nucleic Acid genetics
Abstract

Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease. Here we generated peripheral blood RNA-seq data from 2,116 unrelated individuals and systematically identified context-dependent eQTLs using a hypothesis-free strategy that does not require previous knowledge of the identity of the modifiers. Of the 23,060 significant cis-regulated genes (false discovery rate (FDR) ≤ 0.05), 2,743 (12%) showed context-dependent eQTL effects. The majority of these effects were influenced by cell type composition. A set of 145 cis-eQTLs depended on type I interferon signaling. Others were modulated by specific transcription factors binding to the eQTL SNPs.

Published
2017
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38. A Framework for Discovering, Designing, and Testing MicroProteins to Regulate Synthetic Transcriptional Modules.

Author

Fiume E, de Klein N, Rhee SY, and Magnani E

Subjects
Gene Regulatory Networks genetics, Protein Interaction Maps genetics, Transcription Factors genetics, Gene Expression Regulation genetics, Molecular Biology methods, Proteins genetics, Transcription, Genetic
Abstract

Transcription factors often form protein complexes and give rise to intricate transcriptional networks. The regulation of transcription factor multimerization plays a key role in the fine-tuning of the underlying transcriptional pathways and can be exploited to modulate synthetic transcriptional modules. A novel regulation of protein complex formation is emerging: microProteins-truncated transcription factors-engage in protein-protein interactions with transcriptional complexes and modulate their transcriptional activity. Here, we outline a strategy for the discovery, design, and test of putative miPs to fine-tune the activity of transcription factors regulating synthetic or natural transcriptional circuits.

Published
2016
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