156 results on '"Thio, Chris H. L."'
Search Results
2. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements
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Scholz, Markus, Horn, Katrin, Pott, Janne, Wuttke, Matthias, Kühnapfel, Andreas, Nasr, M. Kamal, Kirsten, Holger, Li, Yong, Hoppmann, Anselm, Gorski, Mathias, Ghasemi, Sahar, Li, Man, Tin, Adrienne, Chai, Jin-Fang, Cocca, Massimiliano, Wang, Judy, Nutile, Teresa, Akiyama, Masato, Åsvold, Bjørn Olav, Bansal, Nisha, Biggs, Mary L., Boutin, Thibaud, Brenner, Hermann, Brumpton, Ben, Burkhardt, Ralph, Cai, Jianwen, Campbell, Archie, Campbell, Harry, Chalmers, John, Chasman, Daniel I., Chee, Miao Ling, Chee, Miao Li, Chen, Xu, Cheng, Ching-Yu, Cifkova, Renata, Daviglus, Martha, Delgado, Graciela, Dittrich, Katalin, Edwards, Todd L., Endlich, Karlhans, Michael Gaziano, J., Giri, Ayush, Giulianini, Franco, Gordon, Scott D., Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hartman, Catharina A., Hayward, Caroline, Heid, Iris M., Hellwege, Jacklyn N., Holleczek, Bernd, Holm, Hilma, Hutri-Kähönen, Nina, Hveem, Kristian, Isermann, Berend, Jonas, Jost B., Joshi, Peter K., Kamatani, Yoichiro, Kanai, Masahiro, Kastarinen, Mika, Khor, Chiea Chuen, Kiess, Wieland, Kleber, Marcus E., Körner, Antje, Kovacs, Peter, Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kuokkanen, Mikko, Kähönen, Mika, Lange, Leslie A., Lash, James P., Lehtimäki, Terho, Li, Hengtong, Lin, Bridget M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K. E., Martin, Nicholas G., Matsuda, Koichi, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., März, Winfried, Nauck, Matthias, Nikus, Kjell, Nolte, Ilja M., Noordam, Raymond, Okada, Yukinori, Olafsson, Isleifur, Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Perola, Markus, Pirastu, Nicola, Polasek, Ozren, Porteous, David J., Poulain, Tanja, Psaty, Bruce M., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Rasheed, Humaira, Reilly, Dermot F., Rice, Kenneth M., Richmond, Anne, Ridker, Paul M., Rotter, Jerome I., Rudan, Igor, Sabanayagam, Charumathi, Salomaa, Veikko, Schneiderman, Neil, Schöttker, Ben, Sims, Mario, Snieder, Harold, Stark, Klaus J., Stefansson, Kari, Stocker, Hannah, Stumvoll, Michael, Sulem, Patrick, Sveinbjornsson, Gardar, Svensson, Per O., Tai, E-Shyong, Taylor, Kent D., Tayo, Bamidele O., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomas, Laurent F., Tremblay, Johanne, Tönjes, Anke, van der Most, Peter J., Vitart, Veronique, Völker, Uwe, Wang, Ya Xing, Wang, Chaolong, Wei, Wen Bin, Whitfield, John B., Wild, Sarah H., Wilson, James F., Winkler, Thomas W., Wong, Tien-Yin, Woodward, Mark, Sim, Xueling, Chu, Audrey Y., Feitosa, Mary F., Thorsteinsdottir, Unnur, Hung, Adriana M., Teumer, Alexander, Franceschini, Nora, Parsa, Afshin, Köttgen, Anna, Schlosser, Pascal, and Pattaro, Cristian
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- 2024
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3. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence
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Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica Cheng, Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., and Sebert, Sylvain
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- 2024
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4. Familial co-aggregation and shared genetics of cardiometabolic disorders and traits: data from the multi-generational Lifelines Cohort Study
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Triatin, Rima D., Chen, Zekai, Ani, Alireza, Wang, Rujia, Hartman, Catharina A., Nolte, Ilja M., Thio, Chris H. L., and Snieder, Harold
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- 2023
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5. DNA methylation trajectories and accelerated epigenetic aging in incident type 2 diabetes
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Fraszczyk, Eliza, Thio, Chris H. L., Wackers, Paul, Dollé, Martijn E. T., Bloks, Vincent W., Hodemaekers, Hennie, Picavet, H. Susan, Stynenbosch, Marjolein, Verschuren, W. M. Monique, Snieder, Harold, Spijkerman, Annemieke M. W., and Luijten, Mirjam
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- 2022
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6. Mediators of the association between educational attainment and type 2 diabetes mellitus: a two-step multivariable Mendelian randomisation study
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Zhang, Jia, Chen, Zekai, Pärna, Katri, van Zon, Sander K. R., Snieder, Harold, and Thio, Chris H. L.
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- 2022
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7. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.
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- 2022
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8. Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease.
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Kamali, Zoha, Esmaeil, Nafiseh, Thio, Chris H. L., Vaez, Ahmad, and Snieder, Harold
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COVID-19 ,PROGNOSIS ,INTERLEUKIN-6 ,COMMUNICABLE diseases ,CRITICALLY ill - Abstract
Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19. Methods: We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies. Results: Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness). Conclusions: These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence
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Choudhary, Priyanka, primary, Monasso, Giulietta S., additional, Karhunen, Ville, additional, Ronkainen, Justiina, additional, Mancano, Giulia, additional, Howe, Caitlin G., additional, Niu, Zhongzheng, additional, Zeng, Xuehuo, additional, Guan, Weihua, additional, Dou, John, additional, Feinberg, Jason I., additional, Mordaunt, Charles, additional, Pesce, Giancarlo, additional, Baïz, Nour, additional, Alfano, Rossella, additional, Martens, Dries S., additional, Wang, Congrong, additional, Isaevska, Elena, additional, Keikkala, Elina, additional, Mustaniemi, Sanna, additional, Thio, Chris H. L., additional, Fraszczyk, Eliza, additional, Tobi, Elmar W., additional, Starling, Anne P., additional, Cosin-Tomas, Marta, additional, Urquiza, Jose, additional, Röder, Stefan, additional, Hoang, Thanh T., additional, Page, Christian, additional, Jima, Dereje D., additional, House, John S., additional, Maguire, Rachel L., additional, Ott, Raffael, additional, Pawlow, Xenia, additional, Sirignano, Lea, additional, Zillich, Lea, additional, Malmberg, Anni, additional, Rauschert, Sebastian, additional, Melton, Phillip, additional, Gong, Tong, additional, Karlsson, Robert, additional, Fore, Ruby, additional, Perng, Wei, additional, Laubach, Zachary M., additional, Czamara, Darina, additional, Sharp, Gemma, additional, Breton, Carrie V., additional, Schisterman, Enrique, additional, Yeung, Edwina, additional, Mumford, Sunni L., additional, Fallin, M. Daniele, additional, LaSalle, Janine M., additional, Schmidt, Rebecca J., additional, Bakulski, Kelly M., additional, Annesi-Maesano, Isabella, additional, Heude, Barbara, additional, Nawrot, Tim S., additional, Plusquin, Michelle, additional, Ghantous, Akram, additional, Herceg, Zdenko, additional, Nisticò, Lorenza, additional, Vafeiadi, Marina, additional, Kogevinas, Manolis, additional, Vääräsmäki, Marja, additional, Kajantie, Eero, additional, Snieder, Harold, additional, Corpeleijn, Eva, additional, Steegers-Theunissen, Regine P. M., additional, Yang, Ivana V., additional, Dabelea, Dana, additional, Fossati, Serena, additional, Zenclussen, Ana C., additional, Herberth, Gunda, additional, Magnus, Maria, additional, Håberg, Siri E., additional, London, Stephanie J., additional, Munthe-Kaas, Monica Cheng, additional, Murphy, Susan K., additional, Hoyo, Cathrine, additional, Ziegler, Anette-G, additional, Hummel, Sandra, additional, Witt, Stephanie H., additional, Streit, Fabian, additional, Frank, Josef, additional, Räikkönen, Katri, additional, Lahti, Jari, additional, Huang, Rae-chi, additional, Almqvist, Catarina, additional, Hivert, Marie-France, additional, Jaddoe, Vincent W. V., additional, Järvelin, Marjo-Riitta, additional, Kantomaa, Marko, additional, Felix, Janine F., additional, and Sebert, Sylvain, additional
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- 2023
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10. Meta-analyses identify DNA methylation associated with kidney function and damage
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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
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- 2021
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11. Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
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Tin, Adrienne, Schlosser, Pascal, Matias-Garcia, Pamela R., Thio, Chris H. L., Joehanes, Roby, Liu, Hongbo, Yu, Zhi, Weihs, Antoine, Hoppmann, Anselm, Grundner-Culemann, Franziska, Min, Josine L., Kuhns, Victoria L. Halperin, Adeyemo, Adebowale A., Agyemang, Charles, Ärnlöv, Johan, Aziz, Nasir A., Baccarelli, Andrea, Bochud, Murielle, Brenner, Hermann, Bressler, Jan, Breteler, Monique M. B., Carmeli, Cristian, Chaker, Layal, Coresh, Josef, Corre, Tanguy, Correa, Adolfo, Cox, Simon R., Delgado, Graciela E., Eckardt, Kai-Uwe, Ekici, Arif B., Endlich, Karlhans, Floyd, James S., Fraszczyk, Eliza, Gao, Xu, Gào, Xīn, Gelber, Allan C., 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, Kardia, Sharon L. R., Kasela, Silva, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Kronenberg, Florian, Kühnel, Brigitte, Ladd-Acosta, Christine, Lehtimäki, Terho, Lind, Lars, Liu, Dan, Lloyd-Jones, Donald M., Lorkowski, Stefan, Lu, Ake T., Marioni, Riccardo E., März, Winfried, McCartney, Daniel L., Meeks, Karlijn A. C., Milani, Lili, Mishra, Pashupati P., Nauck, Matthias, Nowak, Christoph, Peters, Annette, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ratliff, Scott M., Reiner, Alex P., Schöttker, Ben, Schwartz, Joel, Sedaghat, Sanaz, Smith, Jennifer A., Sotoodehnia, Nona, Stocker, Hannah R., Stringhini, Silvia, Sundström, Johan, Swenson, Brenton R., van Meurs, Joyce B. J., van Vliet-Ostaptchouk, Jana V., Venema, Andrea, Völker, Uwe, Winkelmann, Juliane, Wolffenbuttel, Bruce H. R., Zhao, Wei, Zheng, Yinan, Loh, Marie, Snieder, Harold, Waldenberger, Melanie, Levy, Daniel, Akilesh, Shreeram, Woodward, Owen M., Susztak, Katalin, Teumer, Alexander, and Köttgen, Anna
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- 2021
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12. Incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients: data from two prospective cohort studies
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Eck, Ruben J., Hulshof, Lisa, Wiersema, Renske, Thio, Chris H. L., Hiemstra, Bart, van den Oever, Niels C. Gritters, Gans, Reinold O. B., van der Horst, Iwan C. C., Meijer, Karina, and Keus, Frederik
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- 2021
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13. DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study
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Luo, Mannan, primary, Walton, Esther, additional, Neumann, Alexander, additional, Thio, Chris H. L., additional, Felix, Janine F., additional, van IJzendoorn, Marinus H., additional, Pappa, Irene, additional, and Cecil, Charlotte A. M., additional
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- 2023
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14. Observational and genetic evidence support a relationship between cardiac autonomic function and blood pressure
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Chen, Zekai, primary, Wang, Siqi, additional, He, Zhen, additional, Tegegne, Balewgizie S., additional, van Roon, Arie M., additional, Holtjer, Judith C. S., additional, van der Harst, Pim, additional, Snieder, Harold, additional, and Thio, Chris H. L., additional
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- 2023
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15. The impact of poverty on mental illness: Emerging evidence of a causal relationship
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Marchi, Mattia, primary, Alkema, Anne, additional, Xia, Charley, additional, Thio, Chris H. L., additional, Chen, Li-Yu, additional, Schalkwijk, Winni, additional, Galeazzi, Gian Maria, additional, Ferrari, Silvia, additional, Pingani, Luca, additional, Kweon, Hyeokmoon, additional, Evans-Lacko, Sara, additional, Hill, William David, additional, and Boks, Marco P. M., additional
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- 2023
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16. DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study.
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Luo, Mannan, Walton, Esther, Neumann, Alexander, Thio, Chris H. L., Felix, Janine F., van IJzendoorn, Marinus H., Pappa, Irene, and Cecil, Charlotte A. M.
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BIOMARKERS ,SCHIZOPHRENIA ,DNA methylation ,HEART ventricles ,GENOME-wide association studies ,PERIPHERAL circulation ,NEURAL development ,CORD blood ,GENES ,DESCRIPTIVE statistics ,HEART physiology ,EPIGENOMICS ,NEURORADIOLOGY - Abstract
Background: Lateral ventricular volume (LVV) enlargement has been repeatedly linked to schizophrenia; yet, what biological factors shape LVV during early development remain unclear. DNA methylation (DNAm), an essential process for neurodevelopment that is altered in schizophrenia, is a key molecular system of interest. Methods: In this study, we conducted the first epigenome‐wide association study of neonatal DNAm in cord blood with LVV in childhood (measured using T1‐weighted brain scans at 10 years), based on data from a large population‐based birth cohort, the Generation R Study (N = 840). Employing both probe‐level and methylation profile score (MPS) approaches, we further examined whether epigenetic modifications identified at birth in cord blood are: (a) also observed cross‐sectionally in childhood using peripheral blood DNAm at age of 10 years (Generation R, N = 370) and (b) prospectively associated with LVV measured in young adulthood in an all‐male sample from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 114). Results: At birth, DNAm levels at four CpGs (annotated to potassium channel tetramerization domain containing 3, KCTD3; SHH signaling and ciliogenesis regulator, SDCCAG8; glutaredoxin, GLRX) prospectively associated with childhood LVV after genome‐wide correction; these genes have been implicated in brain development and psychiatric traits including schizophrenia. An MPS capturing a broader epigenetic profile of LVV – but not individual top hits – showed significant cross‐sectional associations with LVV in childhood in Generation R and prospectively associated with LVV in early adulthood within ALSPAC. Conclusions: This study finds suggestive evidence that DNAm at birth prospectively associates with LVV at different life stages, albeit with small effect sizes. The prediction of MPS on LVV in a childhood sample and an independent male adult sample further underscores the stability and reproducibility of DNAm as a potential marker for LVV. Future studies with larger samples and comparable time points across development are needed to further elucidate how DNAm associates with this clinically relevant brain structure and risk for neuropsychiatric disorders, and what factors explain the identified DNAm profile of LVV at birth. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Effects of Platelet Count on Blood Pressure: Evidence from Observational and Genetic Investigations.
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He, Zhen, Chen, Zekai, de Borst, Martin H., Zhang, Qingying, Snieder, Harold, and Thio, Chris H. L.
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BLOOD platelets ,BLOOD pressure ,PLATELET count ,SYSTOLIC blood pressure ,CONSORTIA ,PATHOLOGICAL physiology ,SENSITIVITY analysis - Abstract
Platelet count has been associated with blood pressure, but whether this association reflects causality remains unclear. To strengthen the evidence, we conducted a traditional observational analysis in the Lifelines Cohort Study (n = 167,785), and performed bi-directional Mendelian randomization (MR) with summary GWAS data from the UK Biobank (n = 350,475) and the International Consortium of Blood Pressure (ICBP) (n = 299,024). Observational analyses showed positive associations between platelet count and blood pressure (OR = 1.12 per SD, 95% CI: 1.10 to 1.14 for hypertension; B = 0.07, 95% CI: 0.07 to 0.08 for SBP; B = 0.07 per SD, 95% CI: 0.06 to 0.07 for DBP). In MR, a genetically predicted higher platelet count was associated with higher SBP (B = 0.02 per SD, 95% CI = 0.00 to 0.04) and DBP (B = 0.03 per SD, 95% CI = 0.01 to 0.05). IVW models and sensitivity analyses of the association between platelet count and DBP were consistent, but not all sensitivity analyses were statistically significant for the platelet count-SBP relation. Our findings indicate that platelet count has modest but significant effects on SBP and DBP, suggesting causality and providing further insight into the pathophysiology of hypertension. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence
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Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica C., Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., Sebert, Sylvain, Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica C., Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., and Sebert, Sylvain
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Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.
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- 2023
19. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
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Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P., Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B., Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y., Bansal, Nisha, Feitosa, Mary F., Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O., van der Most, Peter J., Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan J. L., Baptista, Daniela, Biggs, Mary L., Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J., Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P., Coresh, Josef, Corre, Tanguy, Danesh, John, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F., Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Gansevoort, Ron T., Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B., Hicks, Andrew A., Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M. Arfan, Ingelsson, Erik, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Lange, Leslie A., Langefeld, Carl D., Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C., Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O., Müller-Nurasyid, Martina, Mychaleckyj, Josyf C., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Noordam, Raymond, Connell, Jeffrey O’, Olafsson, Isleifur, Palmer, Nicholette D., Peters, Annette, Podgornaia, Anna I., Ponte, Belen, Poulain, Tanja, Pramstaller, Peter P., Rabelink, Ton J., Raffield, Laura M., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rivadeneira, Fernando, Runz, Heiko, Ryan, Kathleen A., Sabanayagam, Charumathi, Saum, Kai-Uwe, Schöttker, Ben, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Strauch, Konstantin, Stumvoll, Michael, Sun, Benjamin B., Szymczak, Silke, Tai, E-Shyong, Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorsteinsdottir, Unnur, Tönjes, Anke, Tremblay, Johanne, Uitterlinden, André G., van der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Völker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D., Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Böger, Carsten A., Devuyst, Olivier, Edwards, Todd L., Ho, Kevin, Morris, Andrew P., Parsa, Afshin, Pendergrass, Sarah A., Psaty, Bruce M., Rotter, Jerome I., Stefansson, Kari, Wilson, James G., Susztak, Katalin, Snieder, Harold, Heid, Iris M., Scholz, Markus, Butterworth, Adam S., Hung, Adriana M., Pattaro, Cristian, and Köttgen, Anna
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- 2019
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20. Observational and Genetic Evidence for Bidirectional Effects Between Red Blood Cell Traits and Diastolic Blood Pressure.
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He, Zhen, Chen, Zekai, Borst, Martin H de, Zhang, Qingying, Pressure, International Consortium of Blood, Snieder, Harold, and Thio, Chris H L
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DIASTOLIC blood pressure ,ERYTHROCYTES ,DIASTOLE (Cardiac cycle) ,BLOOD pressure ,BLOOD cell count ,ODDS ratio - Abstract
BACKGROUND Previous studies have found associations of red blood cell (RBC) traits (hemoglobin and RBC count) with blood pressure; whether these associations are causal is unknown. METHODS We performed cross-sectional analyses in the Lifelines Cohort Study (n = 167,785). Additionally, we performed bidirectional 2 sample Mendelian randomization (MR) analyses to explore the causal effect of the 2 traits on systolic (SBP) and diastolic blood pressure (DBP), using genetic instrumental variables regarding hemoglobin and RBC identified in UK Biobank (n = 350,475) and International Consortium of Blood Pressure studies for SBP and DBP (n = 757,601). RESULTS In cross-sectional analyses, we observed positive associations with hypertension and blood pressure for both hemoglobin (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.16–1.20 for hypertension; B = 0.11, 95% CI: 0.11–0.12 for SBP; B = 0.11, 95% CI: 0.10–0.11 for DBP, all per SD) and RBC (OR = 1.14, 95% CI: 1.12–1.16 for hypertension; B = 0.11, 95% CI: 0.10–0.12 for SBP; B = 0.08, 95% CI: 0.08–0.09 for DBP, all per SD). MR analyses suggested that higher hemoglobin and RBC cause higher DBP (inverse-variance weighted B = 0.11, 95% CI: 0.07–0.16 for hemoglobin; B = 0.07, 95% CI: 0.04–0.10 for RBC, all per SD). Reverse MR analyses (all per SD) suggested causal effects of DBP on both hemoglobin (B = 0.06, 95% CI: 0.03–0.09) and RBC (B = 0.08, 95% CI: 0.04–0.11). No significant effects on SBP were found. CONCLUSIONS Our results suggest bidirectional causal relationships of hemoglobin and RBC with DBP, but not with SBP. [ABSTRACT FROM AUTHOR]
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- 2023
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21. Sex Hormones and Risk of Aneurysmal Subarachnoid Hemorrhage : A Mendelian Randomization Study
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Molenberg, Rob, Thio, Chris H. L., Aalbers, Marlien W., Uyttenboogaart, Maarten, Larsson, Susanna C., Bakker, Mark K., Ruigrok, Ynte M., Snieder, Harold, van Dijk, J. Marc C., Molenberg, Rob, Thio, Chris H. L., Aalbers, Marlien W., Uyttenboogaart, Maarten, Larsson, Susanna C., Bakker, Mark K., Ruigrok, Ynte M., Snieder, Harold, and van Dijk, J. Marc C.
- Abstract
Background: The risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased in postmenopausal women compared with men of similar age, suggesting a role for sex hormones. We aimed to explore whether sex hormones, and age at menarche/menopause have a causal effect on aSAH risk by conducting a 2-sample MR study (Mendelian randomization). Methods: We obtained sex-specific genetic instruments for serum estradiol, bioavailable testosterone (BioT), SHBG (sex hormone-binding globulin), and age at menarche/menopause from genome-wide association studies. The associated sex-specific aSAH risk was estimated with inverse-variance weighted MR analyses with various statistical sensitivity analyses. Multivariable and cluster MR analyses were performed for BioT and SHBG to account for a genetic and phenotypic correlation between the 2 exposures. The clusters represented (1) single-nucleotide polymorphisms primarily increasing SHBG, with secondary decreasing effects on BioT, and (2) single-nucleotide polymorphisms affecting BioT without affecting SHBG. Results: Univariable MR analyses showed an 18% increased aSAH risk among women per 1-SD increase in genetically determined SHBG levels (odds ratio, 1.18 [95% CI, 1.05–1.34]; P=0.007). Suggestive evidence was identified for a 27% decreased risk of aSAH among women per 1-SD increase in BioT (odds ratio, 0.73 [95% CI, 0.55–0.95]; P=0.02). The latter association disappeared in cluster analysis when only using SHBG-independent variants. MR analyses with variants from the cluster with primary SHBG effects and secondary (opposite) BioT-effects yielded a statistically significant association (odds ratio, 1.21 [95% CI, 1.05–1.40]; P=0.008). No other causal associations were identified. Conclusions: Genetic predisposition to elevated serum levels of SHBG, with secondary lower serum BioT levels, is associated with an increased aSAH risk among women, suggesting that SHBG and BioT causally elevate aSAH risk. Further studies are required to eluci
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- 2022
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22. Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
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Gorski, Mathias, Rasheed, Humaira, Teumer, Alexander, Thomas, Laurent F., Graham, Sarah E., Sveinbjornsson, Gardar, Winkler, Thomas W., Guenther, Felix, Stark, Klaus J., Chai, Jin-Fang, Tayo, Bamidele O., Wuttke, Matthias, Li, Yong, Tin, Adrienne, Ahluwalia, Tarunveer S., Ärnlöv, Johan, Asvold, Bjorn Olav, Bakker, Stephan J. L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Biino, Ginevra, Bohnke, Michael, Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Brumpton, Ben, Carroll, Robert J., Chaker, Layal, Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Chu, Audrey Y., Ciullo, Marina, Cocca, Massimiliano, Cook, James P., Coresh, Josef, Cusi, Daniele, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Evans, Michele K., Feitosa, Mary F., Franke, Andre, Freitag-Wolf, Sandra, Fuchsberger, Christian, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Gieger, Christian, Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hishida, Asahi, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Holm, Hilma, Hoppmann, Anselm, Horn, Katrin, Hutri-Kahonen, Nina, Hveem, Kristian, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Jung, Bettina, Kahonen, Mika, Karabegovic, Irma, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Kramer, Bernhard K., Kuehnel, Brigitte, Kuusisto, Johanna, Laakso, Markku, Lange, Leslie A., Lehtimaki, Terho, Li, Man, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Loos, Ruth J. F., Lukas, Mary Ann, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Matias-Garcia, Pamela R., Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Morris, Andrew P., Mychaleckyj, Josyf C., Nadkarni, Girish N., Naito, Mariko, Nakatochi, Masahiro, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., Nutile, Teresa, O'Donoghue, Michelle L., O'Connell, Jeffrey, Olafsson, Isleifur, Orho-Melander, Marju, Parsa, Afshin, Pendergrass, Sarah A., Penninx, Brenda W. J. H., Pirastu, Mario, Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rheinberger, Myriam, Rice, Kenneth M., Rizzi, Federica, Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Ruggiero, Daniela, Ryan, Kathleen A., Sabanayagam, Charumathi, Salvi, Erika, Schmidt, Helena, Schmidt, Reinhold, Scholz, Markus, Schoettker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Sieber, Karsten B., Sim, Xueling, Sims, Mario, Snieder, Harold, Stanzick, Kira J., Thorsteinsdottir, Unnur, Stocker, Hannah, Strauch, Konstantin, Stringham, Heather M., Sulem, Patrick, Szymczak, Silke, Taylor, Kent D., Thio, Chris H. L., Tremblay, Johanne, Vaccargiu, Simona, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Volker, Uwe, Wakai, Kenji, Waldenberger, Melanie, Wallentin, Lars, Wallner, Stefan, Wang, Judy, Waterworth, Dawn M., White, Harvey D., Willer, Cristen J., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yerges-Armstrong, Laura M., Zimmermann, Martina, Zonderman, Alan B., Bergler, Tobias, Stefansson, Kari, Boger, Carsten A., Pattaro, Cristian, Koettgen, Anna, Kronenberg, Florian, Heid, Iris M., Gorski, Mathias, Rasheed, Humaira, Teumer, Alexander, Thomas, Laurent F., Graham, Sarah E., Sveinbjornsson, Gardar, Winkler, Thomas W., Guenther, Felix, Stark, Klaus J., Chai, Jin-Fang, Tayo, Bamidele O., Wuttke, Matthias, Li, Yong, Tin, Adrienne, Ahluwalia, Tarunveer S., Ärnlöv, Johan, Asvold, Bjorn Olav, Bakker, Stephan J. L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Biino, Ginevra, Bohnke, Michael, Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Brumpton, Ben, Carroll, Robert J., Chaker, Layal, Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Chu, Audrey Y., Ciullo, Marina, Cocca, Massimiliano, Cook, James P., Coresh, Josef, Cusi, Daniele, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Evans, Michele K., Feitosa, Mary F., Franke, Andre, Freitag-Wolf, Sandra, Fuchsberger, Christian, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Gieger, Christian, Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hishida, Asahi, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Holm, Hilma, Hoppmann, Anselm, Horn, Katrin, Hutri-Kahonen, Nina, Hveem, Kristian, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Jung, Bettina, Kahonen, Mika, Karabegovic, Irma, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Kramer, Bernhard K., Kuehnel, Brigitte, Kuusisto, Johanna, Laakso, Markku, Lange, Leslie A., Lehtimaki, Terho, Li, Man, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Loos, Ruth J. F., Lukas, Mary Ann, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Matias-Garcia, Pamela R., Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Morris, Andrew P., Mychaleckyj, Josyf C., Nadkarni, Girish N., Naito, Mariko, Nakatochi, Masahiro, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., Nutile, Teresa, O'Donoghue, Michelle L., O'Connell, Jeffrey, Olafsson, Isleifur, Orho-Melander, Marju, Parsa, Afshin, Pendergrass, Sarah A., Penninx, Brenda W. J. H., Pirastu, Mario, Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rheinberger, Myriam, Rice, Kenneth M., Rizzi, Federica, Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Ruggiero, Daniela, Ryan, Kathleen A., Sabanayagam, Charumathi, Salvi, Erika, Schmidt, Helena, Schmidt, Reinhold, Scholz, Markus, Schoettker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Sieber, Karsten B., Sim, Xueling, Sims, Mario, Snieder, Harold, Stanzick, Kira J., Thorsteinsdottir, Unnur, Stocker, Hannah, Strauch, Konstantin, Stringham, Heather M., Sulem, Patrick, Szymczak, Silke, Taylor, Kent D., Thio, Chris H. L., Tremblay, Johanne, Vaccargiu, Simona, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Volker, Uwe, Wakai, Kenji, Waldenberger, Melanie, Wallentin, Lars, Wallner, Stefan, Wang, Judy, Waterworth, Dawn M., White, Harvey D., Willer, Cristen J., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yerges-Armstrong, Laura M., Zimmermann, Martina, Zonderman, Alan B., Bergler, Tobias, Stefansson, Kari, Boger, Carsten A., Pattaro, Cristian, Koettgen, Anna, Kronenberg, Florian, and Heid, Iris M.
- Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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- 2022
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23. Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile
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Rimbert, Antoine, Yeung, Ming W., Dalila, Nawar, Thio, Chris H. L., Yu, Haojie, Loaiza, Natalia, Oldoni, Federico, van der Graaf, Adriaan, Wang, Siqi, Said, M. Abdullah, Blauw, Lisanne L., Girardeau, Aurore, Bray, Lise, Caillaud, Amandine, Bloks, Vincent W., Marrec, Marie, Mouli, Philippe, Rensen, Patrick C. N., van de Sluis, Bart, Snieder, Harold, Di Filippo, Mathilde, van der Harst, Pim, Tybjaerg-Hansen, Anne, Zimmerman, Philippe, Cariou, Bertrand, Kuivenhoven, Jan Albert, Rimbert, Antoine, Yeung, Ming W., Dalila, Nawar, Thio, Chris H. L., Yu, Haojie, Loaiza, Natalia, Oldoni, Federico, van der Graaf, Adriaan, Wang, Siqi, Said, M. Abdullah, Blauw, Lisanne L., Girardeau, Aurore, Bray, Lise, Caillaud, Amandine, Bloks, Vincent W., Marrec, Marie, Mouli, Philippe, Rensen, Patrick C. N., van de Sluis, Bart, Snieder, Harold, Di Filippo, Mathilde, van der Harst, Pim, Tybjaerg-Hansen, Anne, Zimmerman, Philippe, Cariou, Bertrand, and Kuivenhoven, Jan Albert
- Abstract
Background: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. Methods: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK Biobank. The Lifelines, The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. Results: In the UK Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. Conclusions: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans.
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- 2022
24. Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile.
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Team Onderzoek, Gezonde Vaten, Circulatory Health, Team Medisch, Rimbert, Antoine, Yeung, Ming W, Dalila, Nawar, Thio, Chris H L, Yu, Haojie, Loaiza, Natalia, Oldoni, Federico, van der Graaf, Adriaan, Wang, Siqi, Said, M Abdullah, Blauw, Lisanne L, Girardeau, Aurore, Bray, Lise, Caillaud, Amandine, Bloks, Vincent W, Marrec, Marie, Moulin, Philippe, Rensen, Patrick C N, van de Sluis, Bart, Snieder, Harold, Di Filippo, Mathilde, van der Harst, Pim, Tybjaerg-Hansen, Anne, Zimmerman, Philip, Cariou, Bertrand, Kuivenhoven, Jan Albert, Team Onderzoek, Gezonde Vaten, Circulatory Health, Team Medisch, Rimbert, Antoine, Yeung, Ming W, Dalila, Nawar, Thio, Chris H L, Yu, Haojie, Loaiza, Natalia, Oldoni, Federico, van der Graaf, Adriaan, Wang, Siqi, Said, M Abdullah, Blauw, Lisanne L, Girardeau, Aurore, Bray, Lise, Caillaud, Amandine, Bloks, Vincent W, Marrec, Marie, Moulin, Philippe, Rensen, Patrick C N, van de Sluis, Bart, Snieder, Harold, Di Filippo, Mathilde, van der Harst, Pim, Tybjaerg-Hansen, Anne, Zimmerman, Philip, Cariou, Bertrand, and Kuivenhoven, Jan Albert
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- 2022
25. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Winkler, Thomas W; https://orcid.org/0000-0003-0292-5421, Rasheed, Humaira; https://orcid.org/0000-0002-3331-5864, Teumer, Alexander; https://orcid.org/0000-0002-8309-094X, Gorski, Mathias, Rowan, Bryce X, Stanzick, Kira J, Thomas, Laurent F, Tin, Adrienne; https://orcid.org/0000-0002-4207-5866, Hoppmann, Anselm, Chu, Audrey Y, Tayo, Bamidele, Thio, Chris H L, Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B, Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano; https://orcid.org/0000-0002-1127-7596, Wuttke, Matthias, van der Most, Peter J; https://orcid.org/0000-0001-8450-3518, Yang, Qiong; https://orcid.org/0000-0002-3658-1375, Ghasemi, Sahar, Nutile, Teresa, Li, Yong; https://orcid.org/0000-0003-2651-8791, Pontali, Giulia; https://orcid.org/0000-0002-4521-8981, Günther, Felix, Dehghan, Abbas; https://orcid.org/0000-0001-6403-016X, Correa, Adolfo, Parsa, Afshin, et al, Winkler, Thomas W; https://orcid.org/0000-0003-0292-5421, Rasheed, Humaira; https://orcid.org/0000-0002-3331-5864, Teumer, Alexander; https://orcid.org/0000-0002-8309-094X, Gorski, Mathias, Rowan, Bryce X, Stanzick, Kira J, Thomas, Laurent F, Tin, Adrienne; https://orcid.org/0000-0002-4207-5866, Hoppmann, Anselm, Chu, Audrey Y, Tayo, Bamidele, Thio, Chris H L, Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B, Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano; https://orcid.org/0000-0002-1127-7596, Wuttke, Matthias, van der Most, Peter J; https://orcid.org/0000-0001-8450-3518, Yang, Qiong; https://orcid.org/0000-0002-3658-1375, Ghasemi, Sahar, Nutile, Teresa, Li, Yong; https://orcid.org/0000-0003-2651-8791, Pontali, Giulia; https://orcid.org/0000-0002-4521-8981, Günther, Felix, Dehghan, Abbas; https://orcid.org/0000-0001-6403-016X, Correa, Adolfo, Parsa, Afshin, and et al
- Abstract
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n$_{DM}$ = 178,691, n$_{noDM}$ = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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- 2022
26. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Winkler, Thomas W, Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X, Stanzick, Kira J, Thomas, Laurent F, Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y, Tayo, Bamidele, Thio, Chris H L, Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B, Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J, Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, et al, University of Zurich, and Winkler, Thomas W
- Subjects
1300 General Biochemistry, Genetics and Molecular Biology ,570 Life sciences ,biology ,610 Medicine & health ,2701 Medicine (miscellaneous) ,1100 General Agricultural and Biological Sciences ,10052 Institute of Physiology - Published
- 2022
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27. Genetic Determinants of Serum Calcification Propensity and Cardiovascular Outcomes in the General Population
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de Haan, Amber, primary, Ahmadizar, Fariba, additional, van der Most, Peter J., additional, Thio, Chris H. L., additional, Kamali, Zoha, additional, Ani, Alireza, additional, Ghanbari, Mohsen, additional, Chaker, Layal, additional, van Meurs, Joyce, additional, Ikram, M. Kamran, additional, van Goor, Harry, additional, Bakker, Stephan J. L., additional, van der Harst, Pim, additional, Snieder, Harold, additional, Kavousi, Maryam, additional, Pasch, Andreas, additional, Eijgelsheim, Mark, additional, and de Borst, Martin H., additional
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- 2022
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28. Search for a Functional Genetic Variant Mimicking the Effect of SGLT2 Inhibitor Treatment
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Wang, Siqi, primary, Said, M. Abdullah, additional, Groot, Hilde E., additional, van der Most, Peter J., additional, Thio, Chris H. L., additional, van de Vegte, Yordi J., additional, Verweij, Niek, additional, Snieder, Harold, additional, and van der Harst, Pim, additional
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- 2021
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29. Additional file 1 of Incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients: data from two prospective cohort studies
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Eck, Ruben J., Hulshof, Lisa, Wiersema, Renske, Thio, Chris H. L., Hiemstra, Bart, Oever, Niels C. Gritters Van Den, Gans, Reinold O. B., Horst, Iwan C. C. Van Der, Meijer, Karina, and Keus, Frederik
- Abstract
Additional file 1. Table S1. Prognostic factor definitions. Table S2. Missing data. Table S3. Prognostic factors for PE-LDVT and NLDVT: univariable analyses. Figure S1. Flow-chart of patient inclusion.
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- 2021
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30. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
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Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H. L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J. L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J. F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O'Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W. J. H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Snieder, Harold, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, Heid, Iris M., Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H. L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J. L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J. F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O'Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W. J. H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Snieder, Harold, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, and Heid, Iris M.
- Abstract
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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- 2021
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31. Genetic Determinants of Serum Calcification Propensity and Cardiovascular Outcomes in the General Population
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de Haan, Amber, Ahmadizar, Fariba, van der Most, Peter J, Thio, Chris H L, Kamali, Zoha, Ani, Alireza, Ghanbari, Mohsen, Chaker, Layal, van Meurs, Joyce, Ikram, M Kamran, van Goor, Harry, Bakker, Stephan J L, van der Harst, Pim, Snieder, Harold, Kavousi, Maryam, Pasch, Andreas, Eijgelsheim, Mark, de Borst, Martin H, de Haan, Amber, Ahmadizar, Fariba, van der Most, Peter J, Thio, Chris H L, Kamali, Zoha, Ani, Alireza, Ghanbari, Mohsen, Chaker, Layal, van Meurs, Joyce, Ikram, M Kamran, van Goor, Harry, Bakker, Stephan J L, van der Harst, Pim, Snieder, Harold, Kavousi, Maryam, Pasch, Andreas, Eijgelsheim, Mark, and de Borst, Martin H
- Abstract
Background: Serum calciprotein particle maturation time (T 50), a measure of vascular calcification propensity, is associated with cardiovascular morbidity and mortality. We aimed to identify genetic loci associated with serum T 50 and study their association with cardiovascular disease and mortality. Methods: We performed a genome-wide association study of serum T 50 in 2,739 individuals of European descent participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, followed by a two-sample Mendelian randomization (MR) study to examine causal effects of T 50 on cardiovascular outcomes. Finally, we examined associations between T 50 loci and cardiovascular outcomes in 8,566 community-dwelling participants in the Rotterdam study. Results: We identified three independent genome-wide significant single nucleotide polymorphism (SNPs) in the AHSG gene encoding fetuin-A: rs4917 (p = 1.72 × 10 −101), rs2077119 (p = 3.34 × 10 −18), and rs9870756 (p = 3.10 × 10 −8), together explaining 18.3% of variation in serum T 50. MR did not demonstrate a causal effect of T 50 on cardiovascular outcomes in the general population. Patient-level analyses revealed that the minor allele of rs9870756, which explained 9.1% of variation in T 50, was associated with a primary composite endpoint of all-cause mortality or cardiovascular disease [odds ratio (95% CI) 1.14 (1.01–1.28)] and all-cause mortality alone [1.14 (1.00–1.31)]. The other variants were not associated with clinical outcomes. In patients with type 2 diabetes or chronic kidney disease, the association between rs9870756 and the primary composite endpoint was stronger [OR 1.40 (1.06–1.84), relative excess risk due to interaction 0.54 (0.01–1.08)]. Conclusions: We identified three SNPs in the AHSG gene that explained 18.3% of variability in serum T 50 levels. Only one SNP
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- 2021
32. Search for a Functional Genetic Variant Mimicking the Effect of SGLT2 Inhibitor Treatment
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Team Medisch, Circulatory Health, Wang, Siqi, Said, M Abdullah, Groot, Hilde E, van der Most, Peter J, Thio, Chris H L, van de Vegte, Yordi J, Verweij, Niek, Snieder, Harold, van der Harst, Pim, Team Medisch, Circulatory Health, Wang, Siqi, Said, M Abdullah, Groot, Hilde E, van der Most, Peter J, Thio, Chris H L, van de Vegte, Yordi J, Verweij, Niek, Snieder, Harold, and van der Harst, Pim
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- 2021
33. Genetic Determinants of Serum Calcification Propensity and Cardiovascular Outcomes in the General Population
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Team Medisch, Circulatory Health, de Haan, Amber, Ahmadizar, Fariba, van der Most, Peter J, Thio, Chris H L, Kamali, Zoha, Ani, Alireza, Ghanbari, Mohsen, Chaker, Layal, van Meurs, Joyce, Ikram, M Kamran, van Goor, Harry, Bakker, Stephan J L, van der Harst, Pim, Snieder, Harold, Kavousi, Maryam, Pasch, Andreas, Eijgelsheim, Mark, de Borst, Martin H, Team Medisch, Circulatory Health, de Haan, Amber, Ahmadizar, Fariba, van der Most, Peter J, Thio, Chris H L, Kamali, Zoha, Ani, Alireza, Ghanbari, Mohsen, Chaker, Layal, van Meurs, Joyce, Ikram, M Kamran, van Goor, Harry, Bakker, Stephan J L, van der Harst, Pim, Snieder, Harold, Kavousi, Maryam, Pasch, Andreas, Eijgelsheim, Mark, and de Borst, Martin H
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- 2021
34. Associations of Genetic Factors, Educational Attainment, and Their Interaction With Kidney Function Outcomes
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Thio, Chris H L, primary, van Zon, Sander K R, additional, van der Most, Peter J, additional, Snieder, Harold, additional, Bültmann, Ute, additional, and Gansevoort, Ron T, additional
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- 2020
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35. A catalog of genetic loci associated with kidney function from analyses of a million individuals
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Wuttke, Matthias, Li, Yong, Li, Man, Sieber, Karsten B., Feitosa, Mary F., Gorski, Mathias, Tin, Adrienne, Wang, Lihua, Chu, Audrey Y., Hoppmann, Anselm, Kirsten, Holger, Giri, Ayush, Chai, Jin-Fang, Sveinbjornsson, Gardar, Tayo, Bamidele O., Nutile, Teresa, Fuchsberger, Christian, Marten, Jonathan, Cocca, Massimiliano, Ghasemi, Sahar, Xu, Yizhe, Horn, Katrin, Noce, Damia, van der Most, Peter J., Sedaghat, Sanaz, Yu, Zhi, Akiyama, Masato, Afaq, Saima, Ahluwalia, Tarunveer S., Almgren, Peter, Amin, Najaf, Ärnlöv, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boehnke, Michael, Boerwinkle, Eric, Boissel, Mathilde, Bottinger, Erwin P., Boutin, Thibaud S., Brenner, Hermann, Brumat, Marco, Burkhardt, Ralph, Butterworth, Adam S., Campana, Eric, Campbell, Archie, Campbell, Harry, Canouil, Mickaël, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Chee, Miao-Ling, Chee, Miao-Li, Chen, Xu, Cheng, Ching-Yu, Cheng, Yurong, Christensen, Kaare, Cifkova, Renata, Ciullo, Marina, Pina Concas, Maria, Cook, James P., Coresh, Josef, Corre, Tanguy, Sala, Cinzia Felicita, Cusi, Daniele, Danesh, John, Daw, E. Warwick, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Delgado, Graciela, Demirkan, Ayse, Di Angelantonio, Emanuele, Dittrich, Katalin, Divers, Jasmin, Dorajoo, Rajkumar, Eckardt, Kai-Uwe, Ehret, Georg, Elliott, Paul, Endlich, Karlhans, Evans, Michele K., Felix, Janine F., Foo, Valencia Hui Xian, Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Friedlander, Yechiel, Froguel, Philippe, Gansevoort, Ron T., Gao, He, Gasparini, Paolo, Gaziano, J. Michael, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Giulianini, Franco, Gögele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hartman, Catharina A., Hayward, Caroline, Hellwege, Jacklyn N., Heng, Chew-Kiat, Hickst, Andrew A., Hofer, Edith, Huang, Wei, Hutri-Kähönen, Nina, Hwang, Shih-Jen, ikram, M. Arfan, indridason, Olafur S., Ingelsson, Erik, ising, Marcus, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Jonas, Jost B, Joshi, Peter K., Shilpa Josyula, Navya, Jung, Bettina, Kähönen, Mika, Kamatani, Yoichiro, Kammerer, Candace M., Kanai, Masahiro, Kastarinen, Mika, Kerr, Shona M., Khor, Chiea-Chuen, Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kraja, Aldi T., Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kühnel, Brigitte, Kuokkanen, Mikko, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lange, Leslie A., Langefeld, Carl D., Jen-Mai Lee, Jeannette, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Cohort Study, Lifelines, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J. F., Lucae, Susanne, Ann Lukas, Mary, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Christa Meisinger, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K., Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P., Veteran Program, V. A. Million, Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., Nadkarni, Girish N, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, ilja M., Noordam, Raymond, O’Connell, Jeffrey, O’Donoghue, Michelle L., Olafsson, Isleifur, Oldehinkel, Albertine J., Orho-Melander, Marju, Ouwehand, Willem H., Padmanabhan, Sandosh, Palmer, Nicholette D., Palsson, Runolfur, Penninx, Brenda W. J. H., Perls, Thomas, Perola, Markus, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Podgornaia, Anna I., Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Pramstaller, Peter P., Preuss, Michael H., Prins, Bram P., Province, Michael A., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Ridker, Paul M., Rivadeneira, Fernando, Rizzi, Federica, Roberts, David J., Robino, Antonietta, Rossing, Peter, Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Sabanayagam, Charumathi, Salomaa, Veikko, Salvi, Erika, Saum, Kai-Uwe, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Schupf, Nicole, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Smith, Blair H., Soranzo, Nicole, Spracklen, Cassandra N., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Svensson, Per O., Szymczak, Silke, Tai, E-Shyong, Tajuddin, Salman M., Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorleifsson, Gudmar, Toniolo, Daniela, Tönjes, Anke, Tremblay, Johanne, Tzoulaki, Ioanna, Uitterlinden, André G., Vaccargiu, Simona, van Dam, Rob M., van der Harst, Pim, van Duijn, Cornelia M., Velez Edward, Digna R., Verweij, Niek, Vogelezang, suzanne, Völker, üwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Wallentin, Lars, Wang, Ya Xing, Wang, Chaolong, Waterworth, Dawn M., Bin Wei, Wen, White, Harvey, Whitfield, John B., Wild, Sarah H., Wilson, James F., Wojczynski, Mary K., Wong, Charlene, Wong, Tien-Yin, Xu, Liang, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Weihua, Zonderman, Alan B., Rotter, Jerome I., Bochud, Murielle, Psaty, Bruce M., Vitart, Veronique, Wilson, James G., Dehghan, Abbas, Parsa, Afshin, Chasman, Daniel I., Ho, Kevin, Morris, Andrew P., Devuyst, Olivier, Akilesh, Shreeram, Pendergrass, Sarah A., Sim, Xueling, Böger, Carsten A., Okada, Yukinori, Edwards, Todd L., Snieder, Harold, Stefansson, Kari, Hung, Adriana M., Heid, Iris M., Markus Scholz, Teumer, Alexander, Köttgen, Anna, Pattaro, Cristian, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Internal Medicine, Epidemiology, Erasmus MC other, Pediatrics, Psychiatry, APH - Mental Health, APH - Digital Health, Wuttke, M, Li, Y, Li, M, Sieber, Kb, Feitosa, Mf, Gorski, M, Tin, A, Wang, L, Chu, Ay, Hoppmann, A, Kirsten, H, Giri, A, Chai, Jf, Sveinbjornsson, G, Tayo, Bo, Nutile, T, Fuchsberger, C, Marten, J, Cocca, M, Ghasemi, S, Xu, Y, Horn, K, Noce, D, van der Most, Pj, Sedaghat, S, Yu, Z, Akiyama, M, Afaq, S, Ahluwalia, T, Almgren, P, Amin, N, Ärnlöv, J, Bakker, Sjl, Bansal, N, Baptista, D, Bergmann, S, Biggs, Ml, Biino, G, Boehnke, M, Boerwinkle, E, Boissel, M, Bottinger, Ep, Boutin, T, Brenner, H, Brumat, M, Burkhardt, R, Butterworth, A, Campana, Eric, Campbell, A, Campbell, H, Canouil, M, Carroll, Rj, Catamo, E, Chambers, Jc, Chee, Ml, Chen, X, Cheng, Cy, Cheng, Y, Christensen, K, Cifkova, R, Ciullo, M, Concas, Mp, Cook, Jp, Coresh, J, Corre, T, Sala, Cf, Cusi, D, Danesh, J, Daw, Ew, de Borst, Mh, De Grandi, A, de Mutsert, R, de Vries, Apj, Degenhardt, F, Delgado, G, Demirkan, A, Di Angelantonio, E, Dittrich, K, Divers, J, Dorajoo, R, Eckardt, Ku, Ehret, G, Elliott, P, Endlich, K, Evans, Mk, Felix, Jf, Foo, Vhx, Franco, Oh, Franke, A, Freedman, Bi, Freitag-Wolf, S, Friedlander, Y, Froguel, P, Gansevoort, Rt, Gao, H, Gasparini, P, Gaziano, Jm, Giedraitis, V, Gieger, C, Girotto, G, Giulianini, F, Gögele, M, Gordon, Sd, Gudbjartsson, Df, Gudnason, V, Haller, T, Hamet, P, Harris, Tb, Hartman, Ca, Hayward, C, Hellwege, Jn, Heng, Ck, Hicks, Aa, Hofer, E, Huang, W, Hutri-Kähönen, N, Hwang, Sj, Ikram, Ma, Indridason, O, Ingelsson, E, Ising, M, Jaddoe, Vwv, Jakobsdottir, J, Jonas, Jb, Joshi, Pk, Josyula, N, Jung, B, Kähönen, M, Kamatani, Y, Kammerer, Cm, Kanai, M, Kastarinen, M, Kerr, Sm, Khor, Cc, Kiess, W, Kleber, Me, Koenig, W, Kooner, J, Körner, A, Kovacs, P, Kraja, At, Krajcoviechova, A, Kramer, H, Krämer, Bk, Kronenberg, F, Kubo, M, Kühnel, B, Kuokkanen, M, Kuusisto, J, La Bianca, M, Laakso, M, Lange, La, Langefeld, Cd, Lee, Jj, Lehne, B, Lehtimäki, T, Lieb, W, Lifelines Cohort, Study, Lim, Sc, Lind, L, Lindgren, Cm, Liu, J, Loeffler, M, Loos, Rjf, Lucae, S, Lukas, Ma, Lyytikäinen, Lp, Mägi, R, Magnusson, Pke, Mahajan, A, Martin, Ng, Martins, J, März, W, Mascalzoni, D, Matsuda, K, Meisinger, C, Meitinger, T, Melander, O, Metspalu, A, Mikaelsdottir, Ek, Milaneschi, Y, Miliku, K, Mishra, Pp, V. A., Million Veteran Program, Mohlke, Kl, Mononen, N, Montgomery, Gw, Mook-Kanamori, Do, Mychaleckyj, Jc, Nadkarni, Gn, Nalls, Ma, Nauck, M, Nikus, K, Ning, B, Nolte, Im, Noordam, R, O'Connell, J, O'Donoghue, Ml, Olafsson, I, Oldehinkel, Aj, Orho-Melander, M, Ouwehand, Wh, Padmanabhan, S, Palmer, Nd, Palsson, R, Penninx, Bwjh, Perls, T, Perola, M, Pirastu, M, Pirastu, N, Pistis, G, Podgornaia, Ai, Polasek, O, Ponte, B, Porteous, Dj, Poulain, T, Pramstaller, Pp, Preuss, Mh, Prins, Bp, Province, Ma, Rabelink, Tj, Raffield, Lm, Raitakari, Ot, Reilly, Df, Rettig, R, Rheinberger, M, Rice, Km, Ridker, Pm, Rivadeneira, F, Rizzi, F, Roberts, Dj, Robino, A, Rossing, P, Rudan, I, Rueedi, R, Ruggiero, D, Ryan, Ka, Saba, Y, Sabanayagam, C, Salomaa, V, Salvi, E, Saum, Ku, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, Ca, Schupf, N, Shaffer, Cm, Shi, Y, Smith, Av, Smith, Bh, Soranzo, N, Spracklen, Cn, Strauch, K, Stringham, Hm, Stumvoll, M, Svensson, Po, Szymczak, S, Tai, E, Tajuddin, Sm, Tan, Nyq, Taylor, Kd, Teren, A, Tham, Yc, Thiery, J, Thio, Chl, Thomsen, H, Thorleifsson, G, Toniolo, D, Tönjes, A, Tremblay, J, Tzoulaki, I, Uitterlinden, Ag, Vaccargiu, S, van Dam, Rm, van der Harst, P, van Duijn, Cm, Velez Edward, Dr, Verweij, N, Vogelezang, S, Völker, U, Vollenweider, P, Waeber, G, Waldenberger, M, Wallentin, L, Wang, Yx, Wang, C, Waterworth, Dm, Bin Wei, W, White, H, Whitfield, Jb, Wild, Sh, Wilson, Jf, Wojczynski, Mk, Wong, C, Wong, Ty, Xu, L, Yang, Q, Yasuda, M, Yerges-Armstrong, Lm, Zhang, W, Zonderman, Ab, Rotter, Ji, Bochud, M, Psaty, Bm, Vitart, V, Wilson, Jg, Dehghan, A, Parsa, A, Chasman, Di, Ho, K, Morris, Ap, Devuyst, O, Akilesh, S, Pendergrass, Sa, Sim, X, Böger, Ca, Okada, Y, Edwards, Tl, Snieder, H, Stefansson, K, Hung, Am, Heid, Im, Scholz, M, Teumer, A, Köttgen, A, and Pattaro, C.
- Subjects
catalog ,Inheritance Patterns ,Hasso-Plattner-Institut für Digital Engineering GmbH ,Genome-wide association study ,Disease ,Kidney Function Tests ,Bioinformatics ,DISEASE ,0302 clinical medicine ,Uromodulin/urine ,kidney function ,11 Medical and Health Sciences ,Genetics & Heredity ,ddc:616 ,0303 health sciences ,Kidney ,Genome-wide association ,HERITABILITY ,GENOME-WIDE ASSOCIATION ,COMMON VARIANTS ,RENAL-FUNCTION ,TRANS-EQTLS ,METAANALYSIS ,TRANSPORTER ,CLASSIFICATION ,INTEGRATION ,Chromosome Mapping ,3. Good health ,Phenotype ,medicine.anatomical_structure ,Medical genetics ,Common variants ,Renal function ,Trans-EQTLS ,Metaanalysis ,Heritability ,Transporter ,Life Sciences & Biomedicine ,Glomerular Filtration Rate ,Metaanalysi ,medicine.medical_specialty ,Genotype ,European Continental Ancestry Group ,Quantitative Trait Loci ,Common variant ,Quantitative trait locus ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,V. A. Million Veteran Program ,03 medical and health sciences ,Quantitative Trait, Heritable ,Lifelines Cohort Study ,Uromodulin ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Renal Insufficiency, Chronic ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Science & Technology ,urogenital system ,association ,genetic loci ,06 Biological Sciences ,medicine.disease ,Renal Insufficiency, Chronic/genetics/physiopathology/urine ,Genetic Association Studies/methods ,ddc:000 ,030217 neurology & neurosurgery ,Developmental Biology ,Genome-Wide Association Study ,Kidney disease - Abstract
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
- Published
- 2019
36. Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
- Author
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Tin, Adrienne, Marten, Jonathan, Kuhns, Victoria L. Halperin, Li, Yong, Wuttke, Matthias, Kirsten, Holger, Sieber, Karsten B., Qiu, Chengxiang, Gorski, Mathias, Yu, Zhi, Giri, Ayush, Sveinbjornsson, Gardar, Li, Man, Chu, Audrey Y., Hoppmann, Anselm, O'Connor, Luke J., Prins, Bram, Nutile, Teresa, Noce, Damia, Akiyama, Masato, Cocca, Massimiliano, Ghasemi, Sahar, van Der Most, Peter J., Horn, Katrin, Xu, Yizhe, Fuchsberger, Christian, Sedaghat, Sanaz, Afaq, Saima, Amin, Najaf, Arnlov, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boerwinkle, Eric, Bottinger, Erwin P., Boutin, Thibaud S., Brumat, Marco, Burkhardt, Ralph, Campana, Eric, Campbell, Archie, Campbell, Harry, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Ciullo, Marina, Concas, Maria Pina, Coresh, Josef, Corre, Tanguy, Cusi, Daniele, Felicita, Sala Cinzia, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Rene, de Vries, Aiko P. J., Delgado, Graciela, Demirkan, Ayse, Devuyst, Olivier, Dittrich, Katalin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Evans, Michele K., Gansevoort, Ron T., Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Ggele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hayward, Caroline, Hicks, Andrew A., Hofer, Edith, Holm, Hilma, Huang, Wei, Hutri-Kahonen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Lewis, Raychel M., Ingelsson, Erik, Jakobsdottir, Johanna, Jonsdottir, Ingileif, Jonsson, Helgi, Joshi, Peter K., Josyula, Navya Shilpa, Jung, Bettina, Kahonen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Kerr, Shona M., Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Korner, Antje, Kovacs, Peter, Kramer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kuhnel, Brigitte, La Bianca, Martina, Lange, Leslie A., Lehne, Benjamin, Lehtimaki, Terho, Liu, Jun, Loeffler, Markus, Loos, Ruth J. F., Lyytikainen, Leo-Pekka, Magi, Reedik, Mahajan, Anubha, Martin, Nicholas G., Marz, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Meisinger, Christa, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, ODonnell, Christopher J., Wilson, Otis D., Gaziano, J. Michael, Mishra, Pashupati P., Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mueller-Nurasyid, Martina, Nadkarni, Girish N., Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., Noordam, Raymond, O'Connell, Jeffrey R., Olafsson, Isleifur, Padmanabhan, Sandosh, Penninx, Brenda W. J. H., Perls, Thomas, Peters, Annette, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Preuss, Michael H., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rizzi, Federica, Robino, Antonietta, Rudan, Igor, Krajcoviechova, Alena, Cifkova, Renata, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Salvi, Erika, Schmidt, Helena, Schmidt, Reinhold, Shaffer, Christian M., Smith, Albert, V, Smith, Blair H., Spracklen, Cassandra N., Strauch, Konstantin, Stumvoll, Michael, Sulem, Patrick, Tajuddin, Salman M., Teren, Andrej, Thiery, Joachim, Thio, Chris H. L., Thorsteinsdottir, Unnur, Toniolo, Daniela, Tonjes, Anke, Tremblay, Johanne, Uitterlinden, Andre G., Vaccargiu, Simona, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Voelker, Uwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Whitfield, John B., Wild, Sarah H., Wilson, James F., Yang, Qiong, Zhang, Weihua, Zonderman, Alan B., Bochud, Murielle, Wilson, James G., Pendergrass, Sarah A., Ho, Kevin, Parsa, Afshin, Pramstaller, Peter P., Psaty, Bruce M., Boeger, Carsten A., Snieder, Harold, Butterworth, Adam S., Okada, Yukinori, Edwards, Todd L., Stefansson, Kari, Susztak, Katalin, Scholz, Markus, Heid, Iris M., Hung, Adriana M., Teumer, Alexander, Pattaro, Cristian, Woodward, Owen M., Vitart, Veronique, Koettgen, Anna, Tin, Adrienne, Marten, Jonathan, Kuhns, Victoria L. Halperin, Li, Yong, Wuttke, Matthias, Kirsten, Holger, Sieber, Karsten B., Qiu, Chengxiang, Gorski, Mathias, Yu, Zhi, Giri, Ayush, Sveinbjornsson, Gardar, Li, Man, Chu, Audrey Y., Hoppmann, Anselm, O'Connor, Luke J., Prins, Bram, Nutile, Teresa, Noce, Damia, Akiyama, Masato, Cocca, Massimiliano, Ghasemi, Sahar, van Der Most, Peter J., Horn, Katrin, Xu, Yizhe, Fuchsberger, Christian, Sedaghat, Sanaz, Afaq, Saima, Amin, Najaf, Arnlov, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boerwinkle, Eric, Bottinger, Erwin P., Boutin, Thibaud S., Brumat, Marco, Burkhardt, Ralph, Campana, Eric, Campbell, Archie, Campbell, Harry, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Ciullo, Marina, Concas, Maria Pina, Coresh, Josef, Corre, Tanguy, Cusi, Daniele, Felicita, Sala Cinzia, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Rene, de Vries, Aiko P. J., Delgado, Graciela, Demirkan, Ayse, Devuyst, Olivier, Dittrich, Katalin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Evans, Michele K., Gansevoort, Ron T., Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Ggele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hayward, Caroline, Hicks, Andrew A., Hofer, Edith, Holm, Hilma, Huang, Wei, Hutri-Kahonen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Lewis, Raychel M., Ingelsson, Erik, Jakobsdottir, Johanna, Jonsdottir, Ingileif, Jonsson, Helgi, Joshi, Peter K., Josyula, Navya Shilpa, Jung, Bettina, Kahonen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Kerr, Shona M., Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Korner, Antje, Kovacs, Peter, Kramer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kuhnel, Brigitte, La Bianca, Martina, Lange, Leslie A., Lehne, Benjamin, Lehtimaki, Terho, Liu, Jun, Loeffler, Markus, Loos, Ruth J. F., Lyytikainen, Leo-Pekka, Magi, Reedik, Mahajan, Anubha, Martin, Nicholas G., Marz, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Meisinger, Christa, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, ODonnell, Christopher J., Wilson, Otis D., Gaziano, J. Michael, Mishra, Pashupati P., Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mueller-Nurasyid, Martina, Nadkarni, Girish N., Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., Noordam, Raymond, O'Connell, Jeffrey R., Olafsson, Isleifur, Padmanabhan, Sandosh, Penninx, Brenda W. J. H., Perls, Thomas, Peters, Annette, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Preuss, Michael H., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rizzi, Federica, Robino, Antonietta, Rudan, Igor, Krajcoviechova, Alena, Cifkova, Renata, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Salvi, Erika, Schmidt, Helena, Schmidt, Reinhold, Shaffer, Christian M., Smith, Albert, V, Smith, Blair H., Spracklen, Cassandra N., Strauch, Konstantin, Stumvoll, Michael, Sulem, Patrick, Tajuddin, Salman M., Teren, Andrej, Thiery, Joachim, Thio, Chris H. L., Thorsteinsdottir, Unnur, Toniolo, Daniela, Tonjes, Anke, Tremblay, Johanne, Uitterlinden, Andre G., Vaccargiu, Simona, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Voelker, Uwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Whitfield, John B., Wild, Sarah H., Wilson, James F., Yang, Qiong, Zhang, Weihua, Zonderman, Alan B., Bochud, Murielle, Wilson, James G., Pendergrass, Sarah A., Ho, Kevin, Parsa, Afshin, Pramstaller, Peter P., Psaty, Bruce M., Boeger, Carsten A., Snieder, Harold, Butterworth, Adam S., Okada, Yukinori, Edwards, Todd L., Stefansson, Kari, Susztak, Katalin, Scholz, Markus, Heid, Iris M., Hung, Adriana M., Teumer, Alexander, Pattaro, Cristian, Woodward, Owen M., Vitart, Veronique, and Koettgen, Anna
- Abstract
Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
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- 2019
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37. Educational level and risk of chronic kidney disease: longitudinal data from the PREVEND study
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Thio, Chris H L, primary, Vart, Priya, additional, Kieneker, Lyanne M, additional, Snieder, Harold, additional, Gansevoort, Ron T, additional, and Bültmann, Ute, additional
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- 2018
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38. Educational level and risk of chronic kidney disease: longitudinal data from the PREVEND study.
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Thio, Chris H L, Vart, Priya, Kieneker, Lyanne M, Snieder, Harold, Gansevoort, Ron T, and Bültmann, Ute
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CHRONIC kidney failure , *EDUCATIONAL attainment , *WAIST-hip ratio , *BODY mass index , *GLOMERULAR filtration rate - Abstract
Background The longitudinal association between low education and chronic kidney disease (CKD) and its underlying mechanisms is poorly characterized. We therefore examined the association of low education with incident CKD and change in kidney function, and explored potential mediators of this association. Methods We analysed data on 6078 participants from the community-based Prevention of Renal and Vascular End-stage Disease study. Educational level was categorized into low, medium and high (< secondary, secondary/equivalent, > secondary schooling, respectively). Kidney function was assessed by estimating glomerular filtration rate (eGFR) by serum creatinine and cystatin C at five examinations during ∼11 years of follow-up. Incident CKD was defined as new-onset eGFR <60 mL/min/1.73 m2 and/or urinary albumin ≥30 mg/24 h in those free of CKD at baseline. We estimated main effects with Cox regression and linear mixed models. In exploratory causal mediation analyses, we examined mediation by several potential risk factors. Results Incident CKD was observed in 861 (17%) participants. Lower education was associated with higher rates of incident CKD [low versus high education; hazard ratio (HR) (95% CI) 1.25 (1.05–1.48), Ptrend = 0.009] and accelerated eGFR decline [ B (95% CI) −0.15 (−0.21 to −0.09) mL/min/1.73 m2/year, Ptrend < 0.001]. The association between education and incident CKD was mediated by smoking, potassium excretion, body mass index (BMI), waist-to-hip ratio (WHR) and hypertension. Analysis on annual eGFR change in addition suggested mediation by magnesium excretion, protein intake and diabetes. Conclusions In the general population, we observed an inverse association of educational level with CKD. Diabetes and the modifiable risk factors smoking, poor diet, BMI, WHR and hypertension are suggested to underlie this association. These findings provide support for targeted preventive policies to reduce socioeconomic disparities in kidney disease. [ABSTRACT FROM AUTHOR]
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- 2020
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39. Evaluation of a genetic risk score based on creatinine-estimated glomerular filtration rate and its association with kidney outcomes
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Thio, Chris H L, primary, van der Most, Peter J, additional, Nolte, Ilja M, additional, van der Harst, Pim, additional, Bültmann, Ute, additional, Gansevoort, Ron T, additional, and Snieder, Harold, additional
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- 2017
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40. Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci.
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Thio, Chris H. L., Reznichenko, Anna, van der Most, Peter J., Kamali, Zoha, Vaez, Ahmad, Smit, Johannes H., Penninx, Brenda W. J. H., Haller, Toomas, Mihailov, Evelin, Metspalu, Andres, Damman, Jeffrey, de Borst, Martin H., van der Harst, Pim, Verweij, Niek, Navis, Gerjan J., Gansevoort, Ron T., Nolte, Ilja M., Snieder, Harold, and Lifelines Cohort Study group
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UREA ,SINGLE nucleotide polymorphisms ,SERUM - Abstract
Background: Serum urea level is a heritable trait, commonly used as a diagnostic marker for kidney function. Genome-wide association studies (GWAS) in East-Asian populations identified a number of genetic loci related to serum urea, however there is a paucity of data for European populations.Methods: We performed a two-stage meta-analysis of GWASs on serum urea in 13,312 participants, with independent replication in 7,379 participants of European ancestry.Results: We identified 6 genome-wide significant single nucleotide polymorphisms (SNPs) in or near 6 loci, of which 2 were novel (POU2AF1 and ADAMTS9-AS2). Replication of East-Asian and Scottish data provided evidence for an additional 8 loci. SNPs tag regions previously associated with anthropometric traits, serum magnesium, and urinary albumin-to-creatinine ratio, as well as expression quantitative trait loci for genes preferentially expressed in kidney and gastro-intestinal tissues.Conclusions: Our findings provide insights into the genetic underpinnings of urea metabolism, with potential relevance to kidney function. [ABSTRACT FROM AUTHOR]- Published
- 2019
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41. Evaluation of a genetic risk score based on creatinine-estimated glomerular filtration rate and its association with kidney outcomes.
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Thio, Chris H L, Most, Peter J van der, Nolte, Ilja M, van der Harst, Pim, Bültmann, Ute, Gansevoort, Ron T, and Snieder, Harold
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META-analysis , *CHRONIC kidney failure , *GLOMERULAR filtration rate , *KIDNEY function tests , *SINGLE nucleotide polymorphisms , *CYSTATINS , *GENETICS - Abstract
Background Meta-analysis of cross-sectional genome-wide association studies (GWAS) on creatinine-estimated glomerular filtration rate (eGFRcrea) identified 53 single-nucleotide polymorphisms (SNPs). These SNP effects can be aggregated into a genetic risk score (GRS) for chronic kidney disease (CKD). To assess its clinical utility, we examined associations with creatinine-estimated kidney outcomes, both cross-sectionally and longitudinally. Additionally, we examined associations with cystatin C-estimated kidney outcomes to verify that a GRS based on eGFRcrea SNPs represents the genetics underlying kidney function. Methods In the community-based Prevention of REnal and Vascular ENdstage Disease (PREVEND) study, we assessed eGFRcrea and eGFRcysc at baseline and four follow-up examinations. The GRS comprised 53 SNPs for eGFRcrea weighted for reported effect-sizes. We adjusted for baseline demographics and renal risk factors. Results We included 3649 subjects (median age 49 years, 52% male, median follow-up 11 years, n = 85 baseline CKD, n = 154 incident CKD). At baseline, a higher GRS associated with lower eGFRcrea {adjusted B [95% confidence interval (CI)] = −2.05 (−2.45 to − 1.65) mL/min/1.73 m2, P < 0.001} and higher CKD prevalence [adjusted odds ratio (95% CI) = 1.41 (1.12–1.77), P = 0.002]. During follow-up, a higher GRS associated with higher CKD incidence [adjusted hazard ratio (95% CI) = 1.28 (1.09–1.50), P = 0.004], but no longer significantly after adjustment for baseline eGFR. No significant association with eGFRcrea decline was found. Associations with cystatin C-estimated outcomes were similar. Conclusions The GRS robustly associated with baseline CKD and eGFR, independent of known risk factors. Associations with incident CKD were likely due to low baseline eGFR, not accelerated eGFR decline. The GRS for eGFRcrea likely represents the genetics underlying kidney function, not creatinine metabolism or underlying aetiologies. To improve the clinical utility of GWAS results for CKD, these need to specifically address eGFR decline and CKD incidence. [ABSTRACT FROM AUTHOR]
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- 2018
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42. The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents
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Jaddoe, Vincent W. V., Felix, Janine F., Andersen, Anne-Marie Nybo, Charles, Marie-Aline, Chatzi, Leda, Corpeleijn, Eva, Donner, Nina, Elhakeem, Ahmed, Eriksson, Johan G., Foong, Rachel, Grote, Veit, Haakma, Sido, Harris, Jennifer R., Heude, Barbara, Huang, Rae-Chi, Inskip, Hazel, Järvelin, Marjo-Riitta, Koletzko, Berthold, Lawlor, Deborah A., Lindeboom, Maarten, McEachan, Rosemary R. C., Mikkola, Tuija M., Nader, Johanna L. T., de Moira, Angela Pinot, Pizzi, Costanza, Richiardi, Lorenzo, Sebert, Sylvain, Schwalber, Ameli, Sunyer, Jordi, Swertz, Morris A., Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Duijts, Liesbeth, El Marroun, Hanan, Gaillard, Romy, Santos, Susana, Geurtsen, Madelon L., Kooijman, Marjolein N., Mensink-Bout, Sara M., Vehmeijer, Florianne O. L., Voerman, Ellis, Nieuwenhuijsen, Mark, Basagaña, Xavier, Bustamante, Mariona, Casas, Maribel, de Castro, Montserrat, Cirugeda, Lourdes E., Fernández-Barrés, Sílvia, Fossati, Serena, Garcia, Raquel, Júlvez, Jordi, Lertxundi, Aitana C., Lertxundi, Nerea, Llop, Sabrina, López-Vicente, Mònica, Lopez-Espinosa, Maria-Jose B., Maitre, Lea, Murcia, Mario, Lea, Jose, Urquiza, H., Warembourg, Charline, Zugna, Daniela, Popovic, Maja, Isaevska, Elena, Maule, Milena, Moccia, Chiara, Moirano, Giovenale, Rasella, Davide, Hanson, Mark A., Inskip, Hazel M., Jacob, Chandni Maria, Salika, Theodosia, Cadman, Tim, Strandberg-Larsen, Katrine M., Pedersen, Marie, Vinther, Johan L., Wilson, Paul, Mason, Dan, Yang, Tiffany C., Cardol, Marloes, van Enckevoort, Esther, Hyde, Eleanor, Scholtens, Salome, Snieder, Harold, Thio, Chris H. L., Chatzi, Lida, Margetaki, Katerina C. A., Roumeliotaki, Theano, Nader, Johanna L., Knudsen, Gun Peggy, Magnus, Per, Panico, Lidia, Ichou, Mathieu, de Lauzon-Guillain, Blandine, Dargent-Molina, Patricia, Cornet, Maxime, Florian, Sandra M., Harrar, Faryal, Lepeule, Johanna, Lioret, Sandrine, Melchior, Maria, Plancoulaine, Sabine, Männikkö, Minna, Parmar, Priyanka, Rautio, Nina, Ronkainen, Justiina, Tolvanen, Mimmi, Mikkola, Tuija M, Aumüller, Nicole, Closa-Monasterolo, Ricardo, Escribano, Joaquin, Ferré, Natalia, Gruszfeld, Dariusz, Gürlich, Kathrin, Langhendries, Jean-Paul, Luque, Veronica, Riva, Enrica, Schwarzfischer, Phillipp, Totzauer, Martina, Verduci, Elvira, Xhonneux, Annick, Zaragoza-Jordana, Marta, Schwalber, Amelie, Foong, Rachel E., Hall, Graham L., Lin, Ashleigh, Carson, Jennie, Melton, Phillip, Rauschert, Sebastian, UNIVERSITY OF OULU, Economics, Tinbergen Institute, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University of Helsinki, Helsinki University Hospital Area, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital Universitari de Sant Joan de Reus, Institut d’Investigació Sanitària Pere Virgili, Ciberdem, BIODonostia Research Institute, University of Turin, University of Southampton, University of Bristol [Bristol], IT University of Copenhagen, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bradford Teaching Hospitals NHS Foundation Trust [Bradford, Royaume-Uni], University of Manchester [Manchester], University of Groningen [Groningen], University of Crete [Heraklion] (UOC), University of Southern California (USC), Norwegian Institute of Public Health [Oslo] (NIPH), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), IMIM-Hospital del Mar, Generalitat de Catalunya, Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), University of the Basque Country [Bizkaia] (UPV/EHU), Universitat de València (UV), Conselleria de Sanitat, Laboratorio de Salud Pública de Valencia, European Project: 733206,H2020,H2020-SC1-2016-RTD,LIFECYCLE(2017), Università degli studi di Torino = University of Turin (UNITO), IT University of Copenhagen (ITU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Erasmus MC other, Pediatrics, Lifestyle Medicine (LM), Reproductive Origins of Adult Health and Disease (ROAHD), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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Male ,Parents ,Databases, Factual ,Epidemiology ,Ethnic group ,BLOOD-PRESSURE ,consortium ,030204 cardiovascular system & hematology ,Cohort Studies ,0302 clinical medicine ,Pregnancy ,Risk Factors ,030212 general & internal medicine ,Marketing ,Child ,DNA METHYLATION ,Public, Environmental & Occupational Health ,life course ,Birth cohorts ,birth cohorts ,SDG 10 - Reduced Inequalities ,ASSOCIATION ,non-communicable diseases ,3142 Public health care science, environmental and occupational health ,3. Good health ,Exposome ,PREGNANCY ,Child, Preschool ,Cohort ,Life course approach ,Generation R ,Female ,Life Sciences & Biomedicine ,Environmental Health ,EARLY NUTRITION ,medicine.medical_specialty ,Adolescent ,LifeCycle Project Group ,exposome ,FOLIC-ACID SUPPLEMENTS ,PROFILE ,1117 Public Health and Health Services ,New Consortium ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Consortium ,Life course ,Non-communicable diseases ,European Union ,Noncommunicable Diseases ,Window of opportunity ,Science & Technology ,business.industry ,Public health ,Stressor ,Infant ,Environmental Exposure ,COHORTS ,LIFE_COURSE ,BIRTH-WEIGHT ,Socioeconomic Factors ,GENERATION R ,RISK-FACTORS ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,DATA_ANALYSIS ,business - Abstract
Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life. The LifeCycle project received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle). All study specific acknowledgements and funding are presented in the supplementary materials. This manuscript reflects only the author's view and the Commission is not responsible for any use that may be made of the information it contains
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43. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
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Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P, Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B, Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y, Bansal, Nisha, Feitosa, Mary F, Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O, Van Der Most, Peter J, Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan J L, Baptista, Daniela, Biggs, Mary L, Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J, Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P, Coresh, Josef, Corre, Tanguy, Danesh, John, De Borst, Martin H, De Grandi, Alessandro, De Mutsert, Renée, De Vries, Aiko P J, Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F, Franco, Oscar H, Franke, Andre, Freedman, Barry I, Freitag-Wolf, Sandra, Gansevoort, Ron T, Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B, Hicks, Andrew A, Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M Arfan, Ingelsson, Erik, Jaddoe, Vincent W V, Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K, Kronenberg, Florian, Lange, Leslie A, Langefeld, Carl D, Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M, Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C, Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O, Müller-Nurasyid, Martina, Mychaleckyj, Josyf C, Nauck, Matthias, Nikus, Kjell, Ning, Boting, Noordam, Raymond, Connell, Jeffrey O', Olafsson, Isleifur, Palmer, Nicholette D, Peters, Annette, Podgornaia, Anna I, Ponte, Belen, Poulain, Tanja, Pramstaller, Peter P, Rabelink, Ton J, Raffield, Laura M, Reilly, Dermot F, Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M, Rivadeneira, Fernando, Runz, Heiko, Ryan, Kathleen A, Sabanayagam, Charumathi, Saum, Kai-Uwe, Schöttker, Ben, Shaffer, Christian M, Shi, Yuan, Smith, Albert V, Strauch, Konstantin, Stumvoll, Michael, Sun, Benjamin B, Szymczak, Silke, Tai, E-Shyong, Tan, Nicholas Y Q, Taylor, Kent D, Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H L, Thomsen, Hauke, Thorsteinsdottir, Unnur, Tönjes, Anke, Tremblay, Johanne, Uitterlinden, André G, Van Der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Völker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D, Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Böger, Carsten A, Devuyst, Olivier, Edwards, Todd L, Ho, Kevin, Morris, Andrew P, Parsa, Afshin, Pendergrass, Sarah A, Psaty, Bruce M, Rotter, Jerome I, Stefansson, Kari, Wilson, James G, Susztak, Katalin, Snieder, Harold, Heid, Iris M, Scholz, Markus, Butterworth, Adam S, Hung, Adriana M, Pattaro, Cristian, and Köttgen, Anna
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610 Medicine & health ,360 Social problems & social services ,3. Good health - Abstract
Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
44. A catalog of genetic loci associated with kidney function from analyses of a million individuals
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Wuttke, Matthias, Li, Yong, Li, Man, Sieber, Karsten B, Feitosa, Mary F, Gorski, Mathias, Tin, Adrienne, Wang, Lihua, Chu, Audrey Y, Hoppmann, Anselm, Kirsten, Holger, Giri, Ayush, Chai, Jin-Fang, Sveinbjornsson, Gardar, Tayo, Bamidele O, Nutile, Teresa, Fuchsberger, Christian, Marten, Jonathan, Cocca, Massimiliano, Ghasemi, Sahar, Xu, Yizhe, Horn, Katrin, Noce, Damia, Van Der Most, Peter J, Sedaghat, Sanaz, Yu, Zhi, Akiyama, Masato, Afaq, Saima, Ahluwalia, Tarunveer S, Almgren, Peter, Amin, Najaf, Ärnlöv, Johan, Bakker, Stephan J L, Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L, Biino, Ginevra, Boehnke, Michael, Boerwinkle, Eric, Boissel, Mathilde, Bottinger, Erwin P, Boutin, Thibaud S, Brenner, Hermann, Brumat, Marco, Burkhardt, Ralph, Butterworth, Adam S, Campana, Eric, Campbell, Archie, Campbell, Harry, Canouil, Mickaël, Carroll, Robert J, Catamo, Eulalia, Chambers, John C, Chee, Miao-Ling, Chee, Miao-Li, Chen, Xu, Cheng, Ching-Yu, Cheng, Yurong, Christensen, Kaare, Cifkova, Renata, Ciullo, Marina, Concas, Maria Pina, Cook, James P, Coresh, Josef, Corre, Tanguy, Sala, Cinzia Felicita, Cusi, Daniele, Danesh, John, Daw, E Warwick, De Borst, Martin H, De Grandi, Alessandro, De Mutsert, Renée, De Vries, Aiko P J, Degenhardt, Frauke, Delgado, Graciela, Demirkan, Ayse, Di Angelantonio, Emanuele, Dittrich, Katalin, Divers, Jasmin, Dorajoo, Rajkumar, Eckardt, Kai-Uwe, Ehret, Georg, Elliott, Paul, Endlich, Karlhans, Evans, Michele K, Felix, Janine F, Foo, Valencia Hui Xian, Franco, Oscar H, Franke, Andre, Freedman, Barry I, Freitag-Wolf, Sandra, Friedlander, Yechiel, Froguel, Philippe, Gansevoort, Ron T, Gao, He, Gasparini, Paolo, Gaziano, J Michael, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Giulianini, Franco, Gögele, Martin, Gordon, Scott D, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B, Hartman, Catharina A, Hayward, Caroline, Hellwege, Jacklyn N, Heng, Chew-Kiat, Hicks, Andrew A, Hofer, Edith, Huang, Wei, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M Arfan, Indridason, Olafur S, Ingelsson, Erik, Ising, Marcus, Jaddoe, Vincent W V, Jakobsdottir, Johanna, Jonas, Jost B, Joshi, Peter K, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Kamatani, Yoichiro, Kammerer, Candace M, Kanai, Masahiro, Kastarinen, Mika, Kerr, Shona M, Khor, Chiea-Chuen, Kiess, Wieland, Kleber, Marcus E, Koenig, Wolfgang, Kooner, Jaspal S, Körner, Antje, Kovacs, Peter, Kraja, Aldi T, Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K, Kronenberg, Florian, Kubo, Michiaki, Kühnel, Brigitte, Kuokkanen, Mikko, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lange, Leslie A, Langefeld, Carl D, Lee, Jeannette Jen-Mai, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M, Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J F, Lucae, Susanne, Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K E, Mahajan, Anubha, Martin, Nicholas G, Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K, Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P, Mohlke, Karen L, Mononen, Nina, Montgomery, Grant W, Mook-Kanamori, Dennis O, Mychaleckyj, Josyf C, Nadkarni, Girish N, Nalls, Mike A, Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M, Noordam, Raymond, O'Connell, Jeffrey, O'Donoghue, Michelle L, Olafsson, Isleifur, Oldehinkel, Albertine J, Orho-Melander, Marju, Ouwehand, Willem H, Padmanabhan, Sandosh, Palmer, Nicholette D, Palsson, Runolfur, Penninx, Brenda W J H, Perls, Thomas, Perola, Markus, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Podgornaia, Anna I, Polasek, Ozren, Ponte, Belen, Porteous, David J, Poulain, Tanja, Pramstaller, Peter P, Preuss, Michael H, Prins, Bram P, Province, Michael A, Rabelink, Ton J, Raffield, Laura M, Raitakari, Olli T, Reilly, Dermot F, Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M, Ridker, Paul M, Rivadeneira, Fernando, Rizzi, Federica, Roberts, David J, Robino, Antonietta, Rossing, Peter, Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A, Saba, Yasaman, Sabanayagam, Charumathi, Salomaa, Veikko, Salvi, Erika, Saum, Kai-Uwe, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Schupf, Nicole, Shaffer, Christian M, Shi, Yuan, Smith, Albert V, Smith, Blair H, Soranzo, Nicole, Spracklen, Cassandra N, Strauch, Konstantin, Stringham, Heather M, Stumvoll, Michael, Svensson, Per O, Szymczak, Silke, Tai, E-Shyong, Tajuddin, Salman M, Tan, Nicholas Y Q, Taylor, Kent D, Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H L, Thomsen, Hauke, Thorleifsson, Gudmar, Toniolo, Daniela, Tönjes, Anke, Tremblay, Johanne, Tzoulaki, Ioanna, Uitterlinden, André G, Vaccargiu, Simona, Van Dam, Rob M, Van Der Harst, Pim, Van Duijn, Cornelia M, Velez Edward, Digna R, Verweij, Niek, Vogelezang, Suzanne, Völker, Uwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Wallentin, Lars, Wang, Ya Xing, Wang, Chaolong, Waterworth, Dawn M, Bin Wei, Wen, White, Harvey, Whitfield, John B, Wild, Sarah H, Wilson, James F, Wojczynski, Mary K, Wong, Charlene, Wong, Tien-Yin, Xu, Liang, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M, Zhang, Weihua, Zonderman, Alan B, Rotter, Jerome I, Bochud, Murielle, Psaty, Bruce M, Vitart, Veronique, Wilson, James G, Dehghan, Abbas, Parsa, Afshin, Chasman, Daniel I, Ho, Kevin, Morris, Andrew P, Devuyst, Olivier, Akilesh, Shreeram, Pendergrass, Sarah A, Sim, Xueling, Böger, Carsten A, Okada, Yukinori, Edwards, Todd L, Snieder, Harold, Stefansson, Kari, Hung, Adriana M, Heid, Iris M, Scholz, Markus, Teumer, Alexander, Köttgen, Anna, and Pattaro, Cristian
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urogenital system ,610 Medicine & health ,360 Social problems & social services ,3. Good health - Abstract
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
45. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
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Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P., Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B., Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y., Bansal, Nisha, Feitosa, Mary F., Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O., Van Der Most, Peter J., Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan J. L., Baptista, Daniela, Biggs, Mary L., Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J., Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P., Coresh, Josef, Corre, Tanguy, Danesh, John, De Borst, Martin H., De Grandi, Alessandro, De Mutsert, Renée, De Vries, Aiko P. J., Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F., Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Gansevoort, Ron T., Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B., Hicks, Andrew A., Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M. Arfan, Ingelsson, Erik, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Lange, Leslie A., Langefeld, Carl D., Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C., Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O., Müller-Nurasyid, Martina, Mychaleckyj, Josyf C., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Noordam, Raymond, Connell, Jeffrey O’, Olafsson, Isleifur, Palmer, Nicholette D., Peters, Annette, Podgornaia, Anna I., Ponte, Belen, Poulain, Tanja, Pramstaller, Peter P., Rabelink, Ton J., Raffield, Laura M., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rivadeneira, Fernando, Runz, Heiko, Ryan, Kathleen A., Sabanayagam, Charumathi, Saum, Kai-Uwe, Schöttker, Ben, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Strauch, Konstantin, Stumvoll, Michael, Sun, Benjamin B., Szymczak, Silke, Tai, E-Shyong, Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorsteinsdottir, Unnur, Tönjes, Anke, Tremblay, Johanne, Uitterlinden, André G., Van Der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Völker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D., Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Böger, Carsten A., Devuyst, Olivier, Edwards, Todd L., Ho, Kevin, Morris, Andrew P., Parsa, Afshin, Pendergrass, Sarah A., Psaty, Bruce M., Rotter, Jerome I., Stefansson, Kari, Wilson, James G., Susztak, Katalin, Snieder, Harold, Heid, Iris M., Scholz, Markus, Butterworth, Adam S., Hung, Adriana M., Pattaro, Cristian, and Köttgen, Anna
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692/4022/1585 ,631/208/205/2138 ,45/43 ,article ,3. Good health - Abstract
Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
46. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- Author
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Tobias Hermle, Holger Kirsten, Karsten B. Sieber, Aiko P. J. de Vries, Su Chi Lim, Peter Kovacs, Charumathi Sabanayagam, Carl D. Langefeld, Bernhard K. Krämer, Kent D. Taylor, Janine F. Felix, Belen Ponte, Markus Loeffler, Mary F. Feitosa, Kai-Uwe Eckardt, Jianjun Liu, Katalin Dittrich, Charlene A. Wong, Uwe Völker, Adriana M. Hung, Thomas Meitinger, Anubha Mahajan, Anselm Hoppmann, Erik Ingelsson, Martin H. de Borst, Oscar H. Franco, Niek Verweij, Kai-Uwe Saum, Vilmundur Gudnason, Bram P. Prins, Carsten A. Böger, Terho Lehtimäki, Andrew A. Hicks, Todd L. Edwards, Olivier Devuyst, Peter P. Pramstaller, Katrin Horn, Leslie A. Lange, Johanne Tremblay, Jin-Fang Chai, Sahar Ghasemi, Kjell Nikus, Tanja Poulain, Massimiliano Cocca, Anna Köttgen, Eric Boerwinkle, Barry I. Freedman, Miao-Ling Chee, Man Li, Stephan J. L. Bakker, Tamara B. Harris, Albert V. Smith, Ton J. Rabelink, Dennis O. Mook-Kanamori, Iris M. Heid, Jasmin Divers, Chaolong Wang, Kathleen A. Ryan, Pavel Hamet, Silke Szymczak, Shih-Jen Hwang, Hauke Thomsen, Rainer Rettig, Ayush Giri, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Cristian Pattaro, Andrej Teren, Valencia Hui Xian Foo, Myriam Rheinberger, Audrey Y. Chu, Barbara McMullen, Franziska Grundner-Culemann, Masayuki Yasuda, Murielle Bochud, Martin Gögele, Anke Tönjes, Jeannette Lee, Adrienne Tin, Kevin Ho, Konstantin Strauch, Josef Coresh, Renée de Mutsert, Sandra Freitag-Wolf, Gardar Sveinbjornsson, Yizhe Xu, Katalin Susztak, Tien Yin Wong, Mary L. Biggs, Isleifur Olafsson, Qiong Yang, Antje Körner, Chengxiang Qiu, E-Shyong Tai, Martina Müller-Nurasyid, Ben Schöttker, Jeffrey O' Connell, Mengmeng Chen, Daniel F. Gudbjartsson, Dermot F. Reilly, Vincent W. V. Jaddoe, Damia Noce, Pim van der Harst, Sanaz Sedaghat, Chiea Chuen Khor, Adam S. Butterworth, Mathias Gorski, Robert J. Carroll, James G. Wilson, Johan Ärnlöv, Christa Meisinger, Kenneth Rice, Bettina Jung, Christian M. Shaffer, Unnur Thorsteinsdottir, Matthias Nauck, Shreeram Akilesh, Mika Kähönen, Johanna Jakobsdottir, Melanie Waldenberger, Ralph Burkhardt, Daniela Baptista, John Danesh, Benjamin B. Sun, Karlhans Endlich, Holly Kramer, Frauke Degenhardt, Wolfgang Lieb, Kari Stefansson, Joachim Thiery, Lars Lind, Nicholette D. Palmer, Sarah A. Pendergrass, Suzanne Vogelezang, Peter J. van der Most, Afshin Parsa, Markus Scholz, Florian Kronenberg, Joseph C. Maranville, Laura M. Raffield, Hermann Brenner, Wieland Kiess, Anna I. Podgornaia, Yuan Shi, Tanguy Corre, Miao-Li Chee, Deborah Mascalzoni, Bamidele O. Tayo, Navya Shilpa Josyula, Ching-Yu Cheng, Lea Gerstner, Nisha Bansal, Jerome I. Rotter, Alexander Teumer, Vilmantas Giedraitis, Raymond Noordam, Ron T. Gansevoort, Lihua Wang, Andrew P. Morris, Bruce M. Psaty, Boting Ning, Zhi Yu, Christian Fuchsberger, Matthias Wuttke, Heiko Runz, Annette Peters, Yih Chung Tham, James P. Cook, Yong Li, Chris H. L. Thio, Hilma Holm, Alessandro De Grandi, Jonathan Marten, André G. Uitterlinden, Andre Franke, Nicholas Y. Q. Tan, Otis D. Wilson, Georg Ehret, Cecilia M. Lindgren, Josyf C. Mychaleckyj, Wolfgang Koenig, Harold Snieder, Michael Stumvoll, Kozeta Miliku, M. Arfan Ikram, Teresa Nutile, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands, University of Iceland, Teumer, Alexander [0000-0002-8309-094X], Li, Yong [0000-0003-2651-8791], Wuttke, Matthias [0000-0003-3420-5082], Giri, Ayush [0000-0002-7786-4670], Qiu, Chengxiang [0000-0002-6346-8669], Kirsten, Holger [0000-0002-3126-7950], Tin, Adrienne [0000-0002-4207-5866], Feitosa, Mary F. [0000-0002-0933-2410], Chai, Jin-Fang [0000-0003-3770-1137], Cocca, Massimiliano [0000-0002-1127-7596], Gorski, Mathias [0000-0002-9103-5860], Horn, Katrin [0000-0002-5307-6936], Li, Man [0000-0002-3839-0281], Marten, Jonathan [0000-0001-6916-2014], van der Most, Peter J. [0000-0001-8450-3518], Burkhardt, Ralph [0000-0003-1924-1202], Coresh, Josef [0000-0002-4598-0669], de Borst, Martin H. [0000-0002-4127-8733], Ehret, Georg [0000-0002-5730-0675], Endlich, Karlhans [0000-0001-6052-6061], Felix, Janine F. [0000-0002-9801-5774], Franke, Andre [0000-0003-1530-5811], Freedman, Barry I. [0000-0003-0275-5530], Freitag-Wolf, Sandra [0000-0002-1069-7740], Giedraitis, Vilmantas [0000-0003-3423-2021], Grundner-Culemann, Franziska [0000-0001-9649-281X], Gudnason, Vilmundur [0000-0001-5696-0084], Hicks, Andrew A. [0000-0001-6320-0411], Ikram, M. Arfan [0000-0003-0372-8585], Ingelsson, Erik [0000-0003-2256-6972], Jaddoe, Vincent W. V. [0000-0003-2939-0041], Josyula, Navya Shilpa [0000-0003-2782-8812], Khor, Chiea-Chuen [0000-0002-1128-4729], Koenig, Wolfgang [0000-0002-2064-9603], Kovacs, Peter [0000-0002-0290-5423], Kronenberg, Florian [0000-0003-2229-1120], Lindgren, Cecilia M. [0000-0002-4903-9374], Liu, Jianjun [0000-0002-3255-3019], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Mahajan, Anubha [0000-0001-5585-3420], Mascalzoni, Deborah [0000-0003-4156-1464], Miliku, Kozeta [0000-0002-9614-7191], Müller-Nurasyid, Martina [0000-0003-3793-5910], Mychaleckyj, Josyf C. [0000-0003-2595-0005], Palmer, Nicholette D. [0000-0001-8883-2511], Poulain, Tanja [0000-0003-3825-5829], Raffield, Laura M. [0000-0002-7892-193X], Rice, Kenneth M. [0000-0002-3071-7278], Rivadeneira, Fernando [0000-0001-9435-9441], Sabanayagam, Charumathi [0000-0002-4042-4719], Smith, Albert V. [0000-0003-1942-5845], Sun, Benjamin B. [0000-0001-6347-2281], Szymczak, Silke [0000-0002-8897-9035], Taylor, Kent D. [0000-0002-2756-4370], Thio, Chris H. L. [0000-0003-2623-7172], Uitterlinden, André G. [0000-0002-7276-3387], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Völker, Uwe [0000-0002-5689-3448], Wang, Chaolong [0000-0003-3945-1012], Yang, Qiong [0000-0002-3658-1375], Devuyst, Olivier [0000-0003-3744-4767], Edwards, Todd L. [0000-0003-4318-6119], Ho, Kevin [0000-0002-3054-8697], Morris, Andrew P. [0000-0002-6805-6014], Pendergrass, Sarah A. [0000-0002-0565-6522], Rotter, Jerome I. [0000-0001-7191-1723], Stefansson, Kari [0000-0003-1676-864X], Susztak, Katalin [0000-0002-1005-3726], Scholz, Markus [0000-0002-4059-1779], Butterworth, Adam S. [0000-0002-6915-9015], Hung, Adriana M. [0000-0002-3203-1608], Pattaro, Cristian [0000-0002-4119-0109], Köttgen, Anna [0000-0002-4671-3714], Apollo - University of Cambridge Repository, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Feitosa, Mary F [0000-0002-0933-2410], van der Most, Peter J [0000-0001-8450-3518], de Borst, Martin H [0000-0002-4127-8733], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Hicks, Andrew A [0000-0001-6320-0411], Ikram, M Arfan [0000-0003-0372-8585], Jaddoe, Vincent WV [0000-0003-2939-0041], Lindgren, Cecilia M [0000-0002-4903-9374], Mychaleckyj, Josyf C [0000-0003-2595-0005], Palmer, Nicholette D [0000-0001-8883-2511], Raffield, Laura M [0000-0002-7892-193X], Rice, Kenneth M [0000-0002-3071-7278], Smith, Albert V [0000-0003-1942-5845], Sun, Benjamin B [0000-0001-6347-2281], Taylor, Kent D [0000-0002-2756-4370], Thio, Chris HL [0000-0003-2623-7172], Uitterlinden, André G [0000-0002-7276-3387], Edwards, Todd L [0000-0003-4318-6119], Morris, Andrew P [0000-0002-6805-6014], Pendergrass, Sarah A [0000-0002-0565-6522], Rotter, Jerome I [0000-0001-7191-1723], Butterworth, Adam S [0000-0002-6915-9015], and Hung, Adriana M [0000-0002-3203-1608]
- Subjects
0301 basic medicine ,Drosophila melanogaster/genetics ,Diabetes Mellitus/genetics ,LD SCORE REGRESSION ,030232 urology & nephrology ,45/43 ,General Physics and Astronomy ,Genome-wide association study ,BLOOD-PRESSURE ,Bioinformatics ,GLOMERULAR-FILTRATION-RATE ,Genome-wide association studies ,Diabetes mellitus genetics ,0302 clinical medicine ,Creatinine/urine ,Risk Factors ,Genome-wide ,Phenomics ,lcsh:Science ,ddc:616 ,Regulation of gene expression ,RISK ,Gene knockdown ,Kidney diseases ,Multidisciplinary ,HERITABILITY ,Albuminuria/genetics ,article ,Chromosome Mapping ,Kidney disease ,ddc ,3. Good health ,Drosophila melanogaster ,Creatinine ,Nýrnasjúkdómar ,692/4022/1585 ,Slit diaphragm ,Medical genetics ,medicine.symptom ,Erfðarannsóknir ,Medical Genetics ,medicine.medical_specialty ,Science ,631/208/205/2138 ,610 Medicine & health ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Meta-Analysis as Topic ,360 Social problems & social services ,Diabetes Mellitus ,medicine ,Animals ,Humans ,Albuminuria ,Genetic Predisposition to Disease ,ddc:610 ,EXCRETION RATE ,CARDIOVASCULAR EVENTS ,Genetic association ,Medicinsk genetik ,TRANS-EQTLS ,KIDNEY-DISEASE ,General Chemistry ,030104 developmental biology ,Gene Expression Regulation ,Genetic Loci ,COLLABORATIVE METAANALYSIS ,lcsh:Q ,Genome-Wide Association Study - Abstract
Publisher's version (útgefin grein)., Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria., Competing interests: Karsten B. Sieber is full-time employee of GlaxoSmithKline. Gardar Sveinbjornsson, Daniel F. Gudbjartsson, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are full-time employees of deCODE genetics, Amgen Inc. John Danesh is member of the Novartis Cardiovascular and Metabolic Advisory Board, received grant support from Novartis. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Wolfgang Koenig received modest consultation fees for advisory board meetings from Amgen, DalCor, Kowa, Novartis, Pfizer and Sanofi, and modest personal fees for lectures from Amgen, AstraZeneca, Novartis, Pfizer and Sanofi. Anna I. Podgornaia and Dermot F. Reilly are employees of Merck Sharp Dohme Corp., Whitehouse Station, NJ, USA. Kevin Ho disclosed a research and financial relationship with Sanofi-Genzyme. Bruce M. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Markus Scholz: Consultancy of and grant support from Merck Serono not related to this project. Adam S. Butterworth received grants from MSD, Pfizer, Novartis, Biogen and Bioverativ and personal fees from Novartis. Anna Köttgen received grant support from Gruenenthal not related to this project. The other authors declare no competing interests.
- Published
- 2019
- Full Text
- View/download PDF
47. Blood biomarkers for new-onset hypertension in midlife women: a nested case-control study.
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He Z, Yang P, Lin Q, Thio CHL, Zhang F, Wang R, Wang Y, Snieder H, and Zhang Q
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- Middle Aged, Humans, Female, Case-Control Studies, Blood Pressure physiology, Risk Factors, Obesity complications, Biomarkers, Hypertension
- Abstract
Objective: Midlife in women is associated with an increase in prevalence of hypertension. Little is known on the risk factors of new-onset hypertension among middle-aged women., Methods: In this nested case-control study, 1,430 women aged 40 to 60 years with repeated physical examinations between 2009 and 2019 were recruited. Data included age, body mass index, blood pressure (BP), and a series of blood biomarkers. Participants with hypertension were divided into two case-control samples: 388 cases with episodic new-onset hypertension (ie, one normal BP at the first visit and one abnormal BP during follow-up) each with two age-matched controls (n = 776) and 151 cases with regular new-onset hypertension (ie, normal BP at the first two visits and abnormal BP at two or more follow-up visits) each with three age-matched controls (n = 453). Multivariable-adjusted logistic regression was used to analyze the data., Results: Our data showed very consistent results for episodic and regular new-onset hypertension, respectively, and verified known associations (odds ratio [95% confidence interval], per SD increase) with obesity (body mass index, 1.72 [1.49-1.98] and 1.81 [1.45-2.26]), inflammation (white blood cell count, 1.39 [1.23-1.58] and 1.38 [1.13-1.69]), and metabolic dysregulation (triglycerides, 1.25 [1.09-1.44] and 1.31 [1.08-1.58]; glucose, 1.46 [1.23-1.73] and 1.27 [1.05-1.54]) but, more surprisingly, also revealed positive associations with red blood cell count (1.27 [1.11-1.44] and 1.38 [1.14-1.68]), hemoglobin (1.18 [1.03-1.35] and 1.31 [1.05-1.64]), and platelet count (1.39 [1.20-1.61] and 1.33 [1.09-1.63])., Conclusions: In addition to obesity and metabolic dysregulation, increased hemoglobin and counts of platelets, and red and white blood cells are associated with hypertension in this period. Future study may verify whether these associations are causal in nature and whether these variables are useful in risk stratification., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)
- Published
- 2023
- Full Text
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48. Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile.
- Author
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Rimbert A, Yeung MW, Dalila N, Thio CHL, Yu H, Loaiza N, Oldoni F, van der Graaf A, Wang S, Said MA, Blauw LL, Girardeau A, Bray L, Caillaud A, Bloks VW, Marrec M, Moulin P, Rensen PCN, van de Sluis B, Snieder H, Di Filippo M, van der Harst P, Tybjaerg-Hansen A, Zimmerman P, Cariou B, and Kuivenhoven JA
- Subjects
- Animals, Apolipoproteins B genetics, C-Reactive Protein, Cholesterol, HDL, Cholesterol, LDL, Humans, Mice, Pharmaceutical Preparations, Receptors, G-Protein-Coupled genetics, Atherosclerosis genetics, Atherosclerosis prevention & control, Hypobetalipoproteinemias genetics
- Abstract
Background: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown., Methods: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK Biobank. The Lifelines, The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants., Results: In the UK Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease ( P =0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels., Conclusions: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans.
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- 2022
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49. Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies.
- Author
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Gorski M, Rasheed H, Teumer A, Thomas LF, Graham SE, Sveinbjornsson G, Winkler TW, Günther F, Stark KJ, Chai JF, Tayo BO, Wuttke M, Li Y, Tin A, Ahluwalia TS, Ärnlöv J, Åsvold BO, Bakker SJL, Banas B, Bansal N, Biggs ML, Biino G, Böhnke M, Boerwinkle E, Bottinger EP, Brenner H, Brumpton B, Carroll RJ, Chaker L, Chalmers J, Chee ML, Chee ML, Cheng CY, Chu AY, Ciullo M, Cocca M, Cook JP, Coresh J, Cusi D, de Borst MH, Degenhardt F, Eckardt KU, Endlich K, Evans MK, Feitosa MF, Franke A, Freitag-Wolf S, Fuchsberger C, Gampawar P, Gansevoort RT, Ghanbari M, Ghasemi S, Giedraitis V, Gieger C, Gudbjartsson DF, Hallan S, Hamet P, Hishida A, Ho K, Hofer E, Holleczek B, Holm H, Hoppmann A, Horn K, Hutri-Kähönen N, Hveem K, Hwang SJ, Ikram MA, Josyula NS, Jung B, Kähönen M, Karabegović I, Khor CC, Koenig W, Kramer H, Krämer BK, Kühnel B, Kuusisto J, Laakso M, Lange LA, Lehtimäki T, Li M, Lieb W, Lind L, Lindgren CM, Loos RJF, Lukas MA, Lyytikäinen LP, Mahajan A, Matias-Garcia PR, Meisinger C, Meitinger T, Melander O, Milaneschi Y, Mishra PP, Mononen N, Morris AP, Mychaleckyj JC, Nadkarni GN, Naito M, Nakatochi M, Nalls MA, Nauck M, Nikus K, Ning B, Nolte IM, Nutile T, O'Donoghue ML, O'Connell J, Olafsson I, Orho-Melander M, Parsa A, Pendergrass SA, Penninx BWJH, Pirastu M, Preuss MH, Psaty BM, Raffield LM, Raitakari OT, Rheinberger M, Rice KM, Rizzi F, Rosenkranz AR, Rossing P, Rotter JI, Ruggiero D, Ryan KA, Sabanayagam C, Salvi E, Schmidt H, Schmidt R, Scholz M, Schöttker B, Schulz CA, Sedaghat S, Shaffer CM, Sieber KB, Sim X, Sims M, Snieder H, Stanzick KJ, Thorsteinsdottir U, Stocker H, Strauch K, Stringham HM, Sulem P, Szymczak S, Taylor KD, Thio CHL, Tremblay J, Vaccargiu S, van der Harst P, van der Most PJ, Verweij N, Völker U, Wakai K, Waldenberger M, Wallentin L, Wallner S, Wang J, Waterworth DM, White HD, Willer CJ, Wong TY, Woodward M, Yang Q, Yerges-Armstrong LM, Zimmermann M, Zonderman AB, Bergler T, Stefansson K, Böger CA, Pattaro C, Köttgen A, Kronenberg F, and Heid IM
- Subjects
- Cross-Sectional Studies, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate genetics, Humans, Kidney, Longitudinal Studies, N-Acetylgalactosaminyltransferases genetics, Renal Insufficiency genetics, Renal Insufficiency, Chronic
- Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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50. A Mendelian randomization cytokine screen reveals IL-13 as causal factor in risk of severe COVID-19.
- Author
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Kamali Z, Vonk JM, Thio CHL, Vaez A, and Snieder H
- Subjects
- Cytokines genetics, Genetic Predisposition to Disease, Humans, Interleukin-13 genetics, Polymorphism, Single Nucleotide, Risk Factors, COVID-19, Mendelian Randomization Analysis
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
- Published
- 2022
- Full Text
- View/download PDF
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