32 results on '"Boeger, Carsten A."'
Search Results
2. 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., Günther, Felix, Stark, Klaus J., Chai, Jin-Fang, Tayo, Bamidele O., Wuttke, Matthias, Li, Yong, Tin, Adrienne, Ahluwalia, Tarunveer S., Ärnlöv, Johan, Åsvold, Bjørn Olav, Bakker, Stephan J.L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Biino, Ginevra, Böhnke, 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-Kähönen, Nina, Hveem, Kristian, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Karabegović, Irma, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Kuusisto, Johanna, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Man, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Loos, Ruth J.F., Lukas, Mary Ann, Lyytikäinen, 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, Schöttker, 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, Völker, 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, Böger, Carsten A., Pattaro, Cristian, Köttgen, Anna, Kronenberg, Florian, and Heid, Iris M.
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- 2022
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3. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
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Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E., Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L., Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J.M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Le, Phuong, Feitosa, Mary F., Wojczynski, Mary K., Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Noah, Tsao L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Sankareswaran, Alagu, Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R.H.J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R.B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, He, Karen Y., Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W.J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D.C., Arnett, Donna K., Walker, Mark, Scott, Laura J., Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N.A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, t Hart, Leen M., Elders, Petra J.M., Rader, Daniel J., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J.F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K.E., Boomsma, Dorret I., de Geus, Eco J.C., Cupples, L. Adrienne, van Meurs, Joyce B.J., Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y. Eugene, Ho, Yuk-Lam, Lynch, Julie A., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Struan Grant, Natarajan, Pradeep, Sun, Yan V., Morris, Andrew P., Deloukas, Panos, Peloso, Gina, Assimes, Themistocles L., Willer, Cristen J., Zhu, Xiang, and Brown, Christopher D.
- Published
- 2022
- Full Text
- View/download PDF
4. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
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Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Snieder, Harold, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Abecasis, Goncalo, Baras, Aris, Cantor, Michael, Coppola, Giovanni, Economides, Aris, Lotta, Luca A., Overton, John D., Reid, Jeffrey G., Shuldiner, Alan, Beechert, Christina, Forsythe, Caitlin, Fuller, Erin D., Gu, Zhenhua, Lattari, Michael, Lopez, Alexander, Schleicher, Thomas D., Padilla, Maria Sotiropoulos, Toledo, Karina, Widom, Louis, Wolf, Sarah E., Pradhan, Manasi, Manoochehri, Kia, Ulloa, Ricardo H., Bai, Xiaodong, Balasubramanian, Suganthi, Barnard, Leland, Blumenfeld, Andrew, Eom, Gisu, Habegger, Lukas, Hawes, Alicia, Khalid, Shareef, Maxwell, Evan K., Salerno, William, Staples, Jeffrey C., Jones, Marcus B., Mitnaul, Lyndon J., 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 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, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, and Heid, Iris M.
- Published
- 2021
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5. Periodic breathing is associated with blood pressure above the recommended target in patients with type 2 diabetes
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Schreib, Andreas W., Arzt, Michael, Heid, Iris M., Jung, Bettina, Böger, Carsten A., and Stadler, Stefan
- Published
- 2020
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6. 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, Guenther, 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., Toenjes, Anke, Morgan, Anna, Podgornaia, Anna, I, Peters, Annette, Koerner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry, I, Spedicati, Beatrice, Ponte, Belen, Schoettker, Ben, Brumpton, Ben, Banas, Bernhard, Kraemer, Bernhard K., Jung, Bettina, Asvold, Bjorn 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., Lyytikainen, 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., Gogele, Martin, La Bianca, Martina, 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, Kahonen, 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-Kahonen, 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, Magi, Reedik, Schmidt, Reinhold, de Mutsert, Renee, 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., Lehtimaki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tonu, Haller, Toomas, Thorsteinsdottir, Unnur, Voelker, 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, Marz, 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, Boeger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Koettgen, Anna, Pattaro, Cristian, Heid, Iris M., 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, Guenther, 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., Toenjes, Anke, Morgan, Anna, Podgornaia, Anna, I, Peters, Annette, Koerner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry, I, Spedicati, Beatrice, Ponte, Belen, Schoettker, Ben, Brumpton, Ben, Banas, Bernhard, Kraemer, Bernhard K., Jung, Bettina, Asvold, Bjorn 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., Lyytikainen, 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., Gogele, Martin, La Bianca, Martina, 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, Kahonen, 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-Kahonen, 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, Magi, Reedik, Schmidt, Reinhold, de Mutsert, Renee, 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., Lehtimaki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tonu, Haller, Toomas, Thorsteinsdottir, Unnur, Voelker, 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, Marz, 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, Boeger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Koettgen, Anna, Pattaro, Cristian, and Heid, Iris M.
- Abstract
A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease. 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
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7. High patient unawareness for chronic kidney disease even in later stages - but why is it more frequent in women than in men?
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Stolpe, Susanne, Scholz, Christian, Stang, Andreas, Boeger, Carsten, Jung, Bettina, Kowall, Bernd, Blume, Cornelia, Stolpe, Susanne, Scholz, Christian, Stang, Andreas, Boeger, Carsten, Jung, Bettina, Kowall, Bernd, and Blume, Cornelia
- Abstract
Introduction Chronic kidney failure (CKD) is as common as diabetes or coronary heart disease in a population aged 40 years and older. Although CKD increases the risk of secondary diseases or premature death, patients with CKD are often unaware of their disease. In a recent analysis of German data, unawareness CKD was higher in women than in men. Methods Baseline data from 2010 of 3,305 CKD patients from German cohort studies and registries were analyzed. Stage 1-4 CKD was defined by eGFR (estimated glomerular filtration rate) and albumin-creatinine ratio according to the KDIGO-guideline. Patient knowledge of CKD was coded according to self-report. The proportion of patients without knowledge of CKD and the sex-specific proportion difference (each with 95 % confidence interval) were calculated according to CKD stages and additional comorbidities (diabetes, hypertension, anemia, and cardiovascular disease). In addition, the prevalence ratio (PR) for not knowing about CKD was estimated for women compared to men crude and adjusted for age and other risk factors. Results Women were less likely than men to know about their CKD in all subgroups studied by age, CKD stage, and comorbidities. The proportion difference for CKD awareness increased with higher CKD stage and was 21 percentage points (7.6; 34.6) at the expense of women in CKD stage 4. Among patients with CKD stage 3b and concomitant grade 2 hypertension, 61 % of women versus 45 % of men were unaware of their disease. The PR for CKD unawareness in women compared with men in the fully adjusted model increased from 1.08 (1.00; 1.16) in CKD stage 3a to 1.75 (1.14; 2.68) in CKD stage 4. Conclusion Despite the presence risk factors that necessitate monitoring of renal function, less than half of patients know they have CKD stage 3b or 4. Women are less likely to be aware of their CKD in all subgroups. Possible causes are gender-related differences in primary health care (gender bias) or in patient-doctor communication.
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- 2022
8. Extensive 177Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy–like Picture
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Schäfer, Hannah, Mayr, Sarah, Büttner-Herold, Maike, Knorr, Karina, Steinhelfer, Lisa, Böger, Carsten A., Gschwend, Jürgen E., Heemann, Uwe, Eiber, Matthias, Schmaderer, Christoph, and Tauber, Robert
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- 2023
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9. RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients
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Böger, Carsten A., Fischereder, Michael, Deinzer, Martina, Aslanidis, Charalampos, Schmitz, Gerd, Stubanus, Mike, Banas, Bernhard, Krüger, Bernd, Riegger, Günter A.J., and Krämer, Bernhard K.
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- 2005
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10. Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
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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.
- Published
- 2019
- Full Text
- View/download PDF
11. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- Author
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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, Arnlov, 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, Renee, 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, Gogele, 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, Kahonen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Koerner, Antje, Kovacs, Peter, Kramer, Holly, Kraemer, Bernhard K., Kronenberg, Florian, Lange, Leslie A., Langefeld, Carl D., Lee, Jeannette Jen-Mai, Lehtimaki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jianjun, Loeffler, Markus, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C., Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O., Mueller-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, Schoettker, 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, Tonjes, Anke, Tremblay, Johanne, Uitterlinden, Andre G., Van der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Voelker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D., Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Boeger, 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, Koettgen, Anna, 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, Arnlov, 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, Renee, 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, Gogele, 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, Kahonen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Koerner, Antje, Kovacs, Peter, Kramer, Holly, Kraemer, Bernhard K., Kronenberg, Florian, Lange, Leslie A., Langefeld, Carl D., Lee, Jeannette Jen-Mai, Lehtimaki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jianjun, Loeffler, Markus, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C., Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O., Mueller-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, Schoettker, 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, Tonjes, Anke, Tremblay, Johanne, Uitterlinden, Andre G., Van der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Voelker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D., Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Boeger, 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 Koettgen, Anna
- 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.
- Published
- 2019
- Full Text
- View/download PDF
12. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- Author
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Justice, Anne E., Karaderi, Tugce, Highland, Heather M., Young, Kristin L., Graff, Mariaelisa, Lu, Yingchang, Turcot, Valerie, Auer, Paul L., Fine, Rebecca S., Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W., Locke, Adam E., Medina-Gomez, Carolina, Esko, Tonu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie C. Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyanm, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Markj, Cesana, Giancarlo, Chambers, John C., Chasman, Daniel, I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audreyy, Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., de Denus, Simon, de Mutsert, Renee, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Doerr, Marcus, Drenos, Fotios, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Groves, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jorgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Kraemer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, La Nge, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimaeki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, RuifangLi-Gao, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstroem, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Magi, Reedik, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Mascal, Nicholas G. D., McCarthy, Mark, I, Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, James, A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, N. Icholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Verges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. Andrew, Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, Mohlke, Karen L., Rotter, Jerome, I, Kutalik, Zoltan, Hirschhorn, Joel N., Cupples, L. Adrienne, Loos, Ruth J. F., North, Kari E., Lindgren, Cecilia M., O'Connell, Jeffrey R., Raitakari, Olli T., Lange, Leslie A., Uitterlinden, Andr G., Grove, Megan L., Masca, Nicholas G. D., Luan, Jianan, Wareham, Nicholas J., Esko, Tnu, De Bakker, Paul Iw, Caulfield, Mark J., Mller-Nurasyid, Martina, Justice, Anne E., Karaderi, Tugce, Highland, Heather M., Young, Kristin L., Graff, Mariaelisa, Lu, Yingchang, Turcot, Valerie, Auer, Paul L., Fine, Rebecca S., Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W., Locke, Adam E., Medina-Gomez, Carolina, Esko, Tonu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie C. Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyanm, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Markj, Cesana, Giancarlo, Chambers, John C., Chasman, Daniel, I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audreyy, Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., de Denus, Simon, de Mutsert, Renee, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Doerr, Marcus, Drenos, Fotios, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Groves, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jorgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Kraemer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, La Nge, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimaeki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, RuifangLi-Gao, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstroem, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Magi, Reedik, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Mascal, Nicholas G. D., McCarthy, Mark, I, Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, James, A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, N. Icholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Verges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. Andrew, Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, Mohlke, Karen L., Rotter, Jerome, I, Kutalik, Zoltan, Hirschhorn, Joel N., Cupples, L. Adrienne, Loos, Ruth J. F., North, Kari E., Lindgren, Cecilia M., O'Connell, Jeffrey R., Raitakari, Olli T., Lange, Leslie A., Uitterlinden, Andr G., Grove, Megan L., Masca, Nicholas G. D., Luan, Jianan, Wareham, Nicholas J., Esko, Tnu, De Bakker, Paul Iw, Caulfield, Mark J., and Mller-Nurasyid, Martina
- Abstract
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
- Published
- 2019
- Full Text
- View/download PDF
13. METHYLENE-TETRAHYDROFOLATE-REDUCTASE GENE (C677T) POLYMORPHISM AS A RISK FACTOR FOR CARDIOVASCULAR DISEASE IN PATIENTS WITH NIDDM AND DIABETIC NEPHROPATHY
- Author
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Stubanus, Mike, Boeger, Carsten, Haak, Thomas, Holmer, Stephan R., Fischereder, Michael, and Krämer, Bernhard K.
- Published
- 2003
14. L55M GENOTYPE IN GENDIAN: A PROSPECTIVE CASE CONTROL STUDY EVALUATING THE GENETIC PREDICTORS OF MORBIDITY, MORTALITY AND DIABETIC NEPHROPATHY IN DIABETES MELLITUS TYPE 2
- Author
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Boeger, Carsten, Stubanus, Mike, Deinzer, Martina, Fischereder, Michael, Schmitz, G., and Krämer, Bernhard K.
- Published
- 2003
15. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- Author
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Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hakan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renstrom, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hakan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renstrom, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.
- Abstract
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity., Correction in: Nature Genetics https://doi.org/10.1038/s41588-017-0011-x, published online 22 December 2017. Published online: 3 June 2019https://doi.org/10.1038/s41588-019-0447-2
- Published
- 2018
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16. Rare and low-frequency coding variants alter human adult height
- Author
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Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rueger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valerie, Young, Kristin L, Winkler, Thomas W, Esko, Tonu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blueher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J, de Denus, Simon, de Groot, Mark CH, de Mutsert, Renee, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D, Feitosa, Mary F, Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D, Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, He, Liang, Heid, Iris M, Heikkila, Kauko, Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna MM, Hoyng, Carel B, Huang, Paul L, Hveem, Kristian, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Hakan, Jarvik, Gail P, Jensen, Gorm B, Jhun, Min A, Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jorgensen, Marit E, Jorgensen, Torben, Jousilahti, Pekka, Jukema, J Wouter, Kahali, Bratati, Kahn, Rene S, Kahonen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A, Kitajima, Hidetoshi, Kluivers, Kirsten B, Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Kury, Sebastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A, Lange, Ethan M, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Larson, Eric B, Lee, I-Te, Lehtimaki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A, Lyytikainen, Leo-Pekka, Mackey, David A, Madden, Pamela AF, Manning, Alisa K, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Martin, Nicholas G, Mazul, Angela L, Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L, Mook-Kanamori, Dennis O, Morgan, Anna, Morris, Andrew D, Morris, Andrew P, Mueller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njolstad, Pal R, Nordestgaard, Borge G, Ntalla, Ioanna, O'Connel, Jeffrey R, Oksa, Heikki, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John RB, Person, Thomas N, Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renstrom, Frida, Ridker, Paul M, Rioux, John D, Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert Vernon, Smith, Jennifer A, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Steinthorsdottir, Valgerdur, Stringham, Heather M, Stumvoll, Michael, Surendran, Praveen, 't Hart, Leen M, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorsteinsdottir, Unnur, Thuesen, Betina H, Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, Andre G, Ulivi, Sheila, van der Laan, Sander W, Van Der Leij, Andries R, van Duijn, Cornelia M, van Schoor, Natasja M, van Setten, Jessica, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J, Warren, Helen R, Wessel, Jennifer, Willems, Sara M, Wilson, James G, Witte, Daniel R, Woods, Michael O, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I, Willer, Cristen J, Stefansson, Kari, Borecki, Ingrid B, Liu, Dajiang J, North, Kari E, Heard-Costa, Nancy L, Pers, Tune H, Lindgren, Cecilia M, Oxvig, Claus, Kutalik, Zoltan, Rivadeneira, Fernando, Loos, Ruth JF, Frayling, Timothy M, Hirschhorn, Joel N, Deloukas, Panos, Lettre, Guillaume, Consortium, EPIC-InterAct, Consortium, EPIC-CVD, Consortium, CHD Exome, Consortium, ExomeBP, Consortium, T2D-Genes, Consortium, GoT2D Genes, Consortium, Global Lipids Genetics, Consortium, ReproGen, Investigators, MAGIC, Marouli, Eirini, Graff, Mariaelisa, Medina Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valérie, Young, Kristin L., Winkler, Thomas W., Esko, Tõnu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthia, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bonnycastle, Lori L., Bork Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Coromina, Cox, Amanda J., Cuellar Partida, Gabriel, Danesh, John, Davies, Gail, De Bakker, Paul I. W., De Borst, Gert J., De Denus, Simon, De Groot, Mark C. H., De Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotio, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelo, Farmaki, Aliki Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmanta, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon Larsen, Penny, Gorski, Mathia, Grarup, Niel, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, G. Kee, Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan Håkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jousilahti, Pekka, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thoma, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charle, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, LA BIANCA, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I. Te, Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li Gao, Ruifang, Lin, Honghuang, Lin, Li An, Lin, Xu, Lind, Lar, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andre, Mitchell, Paul, Mohlke, Karen L., Mook Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Müller Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthia, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Ntalla, Ioanna, O'Connel, Jeffrey R., Oksa, Heikki, Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Marku, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, Hart'T, Leen M., Tansey, Katherine E., Tardif, Jean Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Ulivi, Sheila, Van Der Laan, Sander W., Van Der Leij, Andries R., Van Duijn, Cornelia M., Van Schoor, Natasja M., Van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I., Boehnke, Michael, Kathiresan, Sekar, Mccarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Clau, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Pano, Lettre, Guillaume, Pharmacoepidemiology and Clinical Pharmacology, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Internal Medicine, Epidemiology, Obstetrics & Gynecology, Radiology & Nuclear Medicine, Neurology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, British Heart Foundation, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, Action on Hearing Loss, Home Office, National Institutes of Health, Public Health England, EPIC-InterAct Consortium, CHD Exome+ Consortium, ExomeBP Consortium, T2D-Genes Consortium, GoT2D Genes Consortium, Global Lipids Genetics Consortium, ReproGen Consortium, MAGIC Investigators, Physiology, Human genetics, APH - Personalized Medicine, APH - Aging & Later Life, Epidemiology and Data Science, and Amsterdam Reproduction & Development (AR&D)
- Subjects
0301 basic medicine ,Male ,ReproGen Consortium ,Multifactorial Inheritance ,Genome-wide association study ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Androgen ,ADAMTS Proteins ,Gene Frequency ,Missing heritability problem ,MISSING HERITABILITY ,Receptors ,2.1 Biological and endogenous factors ,Pregnancy-Associated Plasma Protein-A ,Aetiology ,Non-U.S. Gov't ,Glycosaminoglycans ,Genetics ,Multidisciplinary ,Genome ,CHD Exome+ Consortium ,Medicine (all) ,Research Support, Non-U.S. Gov't ,T2D-Genes Consortium ,Global Lipids Genetics Consortium ,Multidisciplinary Sciences ,Phenotype ,NADPH Oxidase 4 ,Receptors, Androgen ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Interferon Regulatory Factors ,Science & Technology - Other Topics ,Intercellular Signaling Peptides and Proteins ,Female ,Proteoglycans ,EPIC-InterAct Consortium ,ExomeBP Consortium ,Common disease-common variant ,Human ,Adult ,General Science & Technology ,Biology ,Development ,Research Support ,Article ,GENETIC ARCHITECTURE ,N.I.H ,03 medical and health sciences ,MAGIC Investigators ,Research Support, N.I.H., Extramural ,Somatomedins ,Genetic variation ,MD Multidisciplinary ,Journal Article ,gene, height, rare ,Humans ,Hedgehog Proteins ,Interleukin-11 Receptor alpha Subunit ,Allele ,GENOME-WIDE ASSOCIATION ,Gene ,Allele frequency ,Alleles ,Genetic association ,Genetic association study ,Glycoproteins ,Science & Technology ,MUTATIONS ,Genome, Human ,ta1184 ,Human Genome ,Extramural ,Genetic Variation ,NADPH Oxidases ,ta3121 ,Body Height ,INTERLEUKIN-11 ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,MICE ,030104 developmental biology ,GoT2D Genes Consortium ,Proteolysis ,Procollagen N-Endopeptidase ,Cell Adhesion Molecules - Abstract
Contains fulltext : 169801.pdf (Publisher’s version ) (Closed access) Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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- 2017
17. A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population
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Voskarides, Konstantinos, Stefanou, Charalambos, Pieri, Myrtani, Demosthenous, Panayiota, Felekkis, Kyriakos, Arsali, Maria, Athanasiou, Yiannis, Xydakis, Dimitris, Stylianou, Kostas, Daphnis, Eugenios, Goulielmos, Giorgos, Loizou, Petros, Savige, Judith, Hoehne, Martin, Voelker, Linus A., Benzing, Thomas, Maxwell, Patrick H., Gale, Daniel P., Gorski, Mathias, Boeger, Carsten, Kollerits, Barbara, Kronenberg, Florian, Paulweber, Bernhard, Zavros, Michalis, Pierides, Alkis, Deltas, Constantinos, Voskarides, Konstantinos, Stefanou, Charalambos, Pieri, Myrtani, Demosthenous, Panayiota, Felekkis, Kyriakos, Arsali, Maria, Athanasiou, Yiannis, Xydakis, Dimitris, Stylianou, Kostas, Daphnis, Eugenios, Goulielmos, Giorgos, Loizou, Petros, Savige, Judith, Hoehne, Martin, Voelker, Linus A., Benzing, Thomas, Maxwell, Patrick H., Gale, Daniel P., Gorski, Mathias, Boeger, Carsten, Kollerits, Barbara, Kronenberg, Florian, Paulweber, Bernhard, Zavros, Michalis, Pierides, Alkis, and Deltas, Constantinos
- Abstract
Background Recent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on longterm follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms. Methods We looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD). Two variants were genotyped in a cohort of well-studied adult TBMN patients from 19 Greek-Cypriot families, with a homogeneous genetic background. Patients were categorized as Severe or Mild, based on the presence or not of proteinuria, CRF and ESRD. A larger pooled cohort (HEMATURIA) of 524 patients, including IgA nephropathy patients, was used for verification. Additionally, three large general population cohorts [Framingham Heart Study (FHS), KORAF4 and SAPHIR] were used to investigate if the NEPH3-V353M variant has any renal effect in the general population. Results and conclusions Genotyping for two high-scored variants in 103 TBMN adult patients with founder mutations who were classified as mildly or severely affected, pointed to an association with variant NEPH3-V353M (filtrin). This promising result prompted testing in the larger pooled cohort (HEMATURIA), indicating an association of the 353M variant with disease severity under the dominant model (p = 3.0x10(-3), OR = 6.64 adjusting for gender/age; allelic association: p = 4.2x10(-3) adjusting for patients' kinships). Subsequently, genotyping 6,531 subjects of the Framingham Heart Study (FHS) revealed an association of the homozygous 353M/M genotype with microalbuminuria (p = 1.0x10(-3)). Two further general population cohorts, KORAF4 and SAPHIR confirmed the association, and a meta-analysis of all three cohorts
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- 2017
18. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
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Li, Man, Li, Yong, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander, Huffman, Jennifer E., Tromp, Gerard, Fuchsberger, Christian, Gorski, Mathias, Lyytikainen, Leo-Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S., Arking, Dan E., Bihlmeyer, Nathan A., Boeger, Carsten A., Carroll, Robert J., Chasman, Daniel I., Comelis, Marilyn C., Dehghan, Abbas, Faul, Jessica D., Feitosa, Mary F., Gambaro, Giovanni, Gasparini, Paolo, Giulianini, Franco, Heid, Iris, Huang, Jinyan, Imboden, Medea, Jackson, Anne U., Jeff, Janina, Jhun, Min A., Katz, Ronit, Kifley, Annette, Kilpelainen, Tuomas, Kumar, Ashish, Laakso, Markku, Li-Gao, Ruifang, Lohman, Kurt, Lu, Yingchang, Maegi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L., Mook-Kanamori, Dennis O., Robino, Antonietta, Ruderfer, Douglas, Salvi, Erika, Schick, Ursula M., Schulz, Christina-Alexandra, Smith, Albert V., Smith, Jennifer A., Traglia, Michela, Yerges-Armstrong, Laura M., Zhao, Wei, Goodarzi, Mark O., Kraja, Aldi T., Liu, Chunyu, Wessel, Jennifer, Boerwinkle, Eric, Borecki, Ingrid B., Bork-Jensen, Jette, Bottinger, Erwin P., Braga, Daniele, Brandslund, Ivan, Brody, Jennifer A., Campbell, Archie, Carey, David J., Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C., Cusi, Daniele, de Boer, Ian H., de Vries, Aiko P. J., Denny, Joshua C., Devuyst, Olivier, Dreisbach, Albert W., Endlich, Karlhans, Esko, Tonu, Franco, Oscar H., Fulop, Tibor, Gerhard, Glenn S., Gluemer, Charlotte, Gottesman, Omri, Grarup, Niels, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B., Husemoen, Lise Lotte N., Jackson, Rebecca D., Jorgensen, Torben, Jorgensen, Marit E., Kaehoenen, Mika, Kardia, Sharon L. R., Koenig, Wolfgang, Kooperberg, Charles, Kriebel, Jennifer, Launer, Lenore J., Lauritzen, Torsten, Lehtimaki, Terho, Levy, Daniel, Linksted, Pamela, Linneberg, Allan, Liu, Yongmei, Loos, Ruth J. F., Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andres, Mitchell, Paul, Nauck, Matthias, Nuernberg, Peter, Orho-Melander, Marju, Parsa, Afshin, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Porteous, David, Probst-Hensch, Nicole M., Psaty, Bruce M., Qi, Lu, Raitakari, Olli T., Reiner, Alex P., Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando, Rossouw, Jacques E., Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela, Turner, Stephen T., Uitterlinden, Andre G., Ulivi, Sheila, Velayutham, Dinesh, Voelker, Uwe, Volzke, Henry, Waldenberger, Melanie, Wang, Jie Jin, Weir, David R., Witte, Daniel, Kuivaniemi, Helena, Fox, Caroline S., Franceschini, Nora, Goessling, Wolfram, Koettgen, Anna, Chu, Audrey Y., Li, Man, Li, Yong, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander, Huffman, Jennifer E., Tromp, Gerard, Fuchsberger, Christian, Gorski, Mathias, Lyytikainen, Leo-Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S., Arking, Dan E., Bihlmeyer, Nathan A., Boeger, Carsten A., Carroll, Robert J., Chasman, Daniel I., Comelis, Marilyn C., Dehghan, Abbas, Faul, Jessica D., Feitosa, Mary F., Gambaro, Giovanni, Gasparini, Paolo, Giulianini, Franco, Heid, Iris, Huang, Jinyan, Imboden, Medea, Jackson, Anne U., Jeff, Janina, Jhun, Min A., Katz, Ronit, Kifley, Annette, Kilpelainen, Tuomas, Kumar, Ashish, Laakso, Markku, Li-Gao, Ruifang, Lohman, Kurt, Lu, Yingchang, Maegi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L., Mook-Kanamori, Dennis O., Robino, Antonietta, Ruderfer, Douglas, Salvi, Erika, Schick, Ursula M., Schulz, Christina-Alexandra, Smith, Albert V., Smith, Jennifer A., Traglia, Michela, Yerges-Armstrong, Laura M., Zhao, Wei, Goodarzi, Mark O., Kraja, Aldi T., Liu, Chunyu, Wessel, Jennifer, Boerwinkle, Eric, Borecki, Ingrid B., Bork-Jensen, Jette, Bottinger, Erwin P., Braga, Daniele, Brandslund, Ivan, Brody, Jennifer A., Campbell, Archie, Carey, David J., Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C., Cusi, Daniele, de Boer, Ian H., de Vries, Aiko P. J., Denny, Joshua C., Devuyst, Olivier, Dreisbach, Albert W., Endlich, Karlhans, Esko, Tonu, Franco, Oscar H., Fulop, Tibor, Gerhard, Glenn S., Gluemer, Charlotte, Gottesman, Omri, Grarup, Niels, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B., Husemoen, Lise Lotte N., Jackson, Rebecca D., Jorgensen, Torben, Jorgensen, Marit E., Kaehoenen, Mika, Kardia, Sharon L. R., Koenig, Wolfgang, Kooperberg, Charles, Kriebel, Jennifer, Launer, Lenore J., Lauritzen, Torsten, Lehtimaki, Terho, Levy, Daniel, Linksted, Pamela, Linneberg, Allan, Liu, Yongmei, Loos, Ruth J. F., Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andres, Mitchell, Paul, Nauck, Matthias, Nuernberg, Peter, Orho-Melander, Marju, Parsa, Afshin, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Porteous, David, Probst-Hensch, Nicole M., Psaty, Bruce M., Qi, Lu, Raitakari, Olli T., Reiner, Alex P., Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando, Rossouw, Jacques E., Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela, Turner, Stephen T., Uitterlinden, Andre G., Ulivi, Sheila, Velayutham, Dinesh, Voelker, Uwe, Volzke, Henry, Waldenberger, Melanie, Wang, Jie Jin, Weir, David R., Witte, Daniel, Kuivaniemi, Helena, Fox, Caroline S., Franceschini, Nora, Goessling, Wolfram, Koettgen, Anna, and Chu, Audrey Y.
- Abstract
Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (n(stage1);111,666;n(stage2): 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; P-stage1<3.7 x10(-7)), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4x 10(-8) by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.
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- 2017
19. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
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Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, Loos, Ruth J. F., Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, and Loos, Ruth J. F.
- Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap, Correction in: PLOS Genetics, Vol. 12, nr 6, s. e1006166DOI: 10.1371/journal.pgen.1006166
- Published
- 2015
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20. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- Author
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Parsa, Afshin, Fuchsberger, Christian, Koettgen, Anna, O'Seaghdha, Conall M., Pattaro, Cristian, de Andrade, Mariza, Chasman, Daniel I., Teumer, Alexander, Endlich, Karlhans, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Kim, Young J., Taliun, Daniel, Li, Man, Feitosa, Mary, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C., Glazer, Nicole, Isaacs, Aaron, Rao, Madhumathi, Smith, Albert V., O'Connell, Jeffrey R., Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Hwang, Shih-Jen, Atkinson, Elizabeth J., Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa, Toenjes, Anke, Dehghan, Abbas, Couraki, Vincent, Holliday, Elizabeth G., Sorice, Rossella, Kutalik, Zoltan, Lehtimaeki, Terho, Esko, Tonu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y., Murgia, Federico, Trompet, Stella, Imboden, Medea, Kollerits, Barbara, Pistis, Giorgio, Harris, Tamara B., Launer, Lenore J., Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D., Boerwinkle, Eric, Schmidt, Helena, Hofer, Edith, Hu, Frank, Demirkan, Ayse, Oostra, Ben A., Turner, Stephen T., Ding, Jingzhong, Andrews, Jeanette S., Freedman, Barry I., Giulianini, Franco, Koenig, Wolfgang, Illig, Thomas, Doering, Angela, Wichmann, H. -Erich, Zgaga, Lina, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E., Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H., Wright, Alan F., Campbell, Harry, Ellinghaus, David, Noethlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K., Nauck, Matthias, Stracke, Sylvia, Voelker, Uwe, Voelzke, Henry, Kovacs, Peter, Stumvoll, Michael, Maegi, Reedik, Hofman, Albert, Uitterlinden, Andre G., Rivadeneira, Fernando, Aulchenko, Yurii S., Polasek, Ozren, Hastie, Nick, Vitart, Veronique, Helmer, Catherine, Wang, Jie Jin, Stengel, Benedicte, Ruggiero, Daniela, Bergmann, Sven, Kaehoenen, Mika, Viikari, Jorma, Nikopensius, Tiit, Province, Michael, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Kraemer, Bernhard K., Portas, Laura, Ford, Ian, Buckley, Brendan M., Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Sala, Cinzia, Mitchell, Paul, Ciullo, Marina, Vollenweider, Peter, Raitakari, Olli, Metspalu, Andres, Palmer, Colin, Gasparini, Paolo, Pirastu, Mario, Jukema, J. Wouter, Probst-Hensch, Nicole M., Kronenberg, Florian, Toniolo, Daniela, Gudnason, Vilmundur, Shuldiner, Alan R., Coresh, Josef, Schmidt, Reinhold, Ferrucci, Luigi, Van Duijn, Cornelia M., Borecki, Ingrid, Kardia, Sharon L. R., Liu, Yongmei, Curhan, Gary C., Rudan, Igor, Gyllensten, Ulf, Wilson, James F., Franke, Andre, Pramstaller, Peter P., Rettig, Rainer, Prokopenko, Inga, Witteman, Jacqueline, Hayward, Caroline, Ridker, Paul M., Bochud, Murielle, Heid, Iris M., Siscovick, David S., Fox, Caroline S., Kao, W. Linda, Boeger, Carsten A., Parsa, Afshin, Fuchsberger, Christian, Koettgen, Anna, O'Seaghdha, Conall M., Pattaro, Cristian, de Andrade, Mariza, Chasman, Daniel I., Teumer, Alexander, Endlich, Karlhans, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Kim, Young J., Taliun, Daniel, Li, Man, Feitosa, Mary, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C., Glazer, Nicole, Isaacs, Aaron, Rao, Madhumathi, Smith, Albert V., O'Connell, Jeffrey R., Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Hwang, Shih-Jen, Atkinson, Elizabeth J., Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa, Toenjes, Anke, Dehghan, Abbas, Couraki, Vincent, Holliday, Elizabeth G., Sorice, Rossella, Kutalik, Zoltan, Lehtimaeki, Terho, Esko, Tonu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y., Murgia, Federico, Trompet, Stella, Imboden, Medea, Kollerits, Barbara, Pistis, Giorgio, Harris, Tamara B., Launer, Lenore J., Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D., Boerwinkle, Eric, Schmidt, Helena, Hofer, Edith, Hu, Frank, Demirkan, Ayse, Oostra, Ben A., Turner, Stephen T., Ding, Jingzhong, Andrews, Jeanette S., Freedman, Barry I., Giulianini, Franco, Koenig, Wolfgang, Illig, Thomas, Doering, Angela, Wichmann, H. -Erich, Zgaga, Lina, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E., Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H., Wright, Alan F., Campbell, Harry, Ellinghaus, David, Noethlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K., Nauck, Matthias, Stracke, Sylvia, Voelker, Uwe, Voelzke, Henry, Kovacs, Peter, Stumvoll, Michael, Maegi, Reedik, Hofman, Albert, Uitterlinden, Andre G., Rivadeneira, Fernando, Aulchenko, Yurii S., Polasek, Ozren, Hastie, Nick, Vitart, Veronique, Helmer, Catherine, Wang, Jie Jin, Stengel, Benedicte, Ruggiero, Daniela, Bergmann, Sven, Kaehoenen, Mika, Viikari, Jorma, Nikopensius, Tiit, Province, Michael, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Kraemer, Bernhard K., Portas, Laura, Ford, Ian, Buckley, Brendan M., Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Sala, Cinzia, Mitchell, Paul, Ciullo, Marina, Vollenweider, Peter, Raitakari, Olli, Metspalu, Andres, Palmer, Colin, Gasparini, Paolo, Pirastu, Mario, Jukema, J. Wouter, Probst-Hensch, Nicole M., Kronenberg, Florian, Toniolo, Daniela, Gudnason, Vilmundur, Shuldiner, Alan R., Coresh, Josef, Schmidt, Reinhold, Ferrucci, Luigi, Van Duijn, Cornelia M., Borecki, Ingrid, Kardia, Sharon L. R., Liu, Yongmei, Curhan, Gary C., Rudan, Igor, Gyllensten, Ulf, Wilson, James F., Franke, Andre, Pramstaller, Peter P., Rettig, Rainer, Prokopenko, Inga, Witteman, Jacqueline, Hayward, Caroline, Ridker, Paul M., Bochud, Murielle, Heid, Iris M., Siscovick, David S., Fox, Caroline S., Kao, W. Linda, and Boeger, Carsten A.
- Abstract
Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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- 2013
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21. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
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Pattaro, Cristian, Koettgen, Anna, Teumer, Alexander, Garnaas, Maija, Boeger, Carsten A., Fuchsberger, Christian, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C., O'Seaghdha, Conall M., Glazer, Nicole, Isaacs, Aaron, Liu, Ching-Ti, Smith, Albert V., O'Connell, Jeffrey R., Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Johnson, Andrew D., Gierman, Hinco J., Feitosa, Mary, Hwang, Shih-Jen, Atkinson, Elizabeth J., Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa, Toenjes, Anke, Dehghan, Abbas, Chouraki, Vincent, Holliday, Elizabeth G., Sorice, Rossella, Kutalik, Zoltan, Lehtimaeki, Terho, Esko, Tonu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y., Murgia, Federico, Trompet, Stella, Imboden, Medea, Kollerits, Barbara, Pistis, Giorgio, Harris, Tamara B., Launer, Lenore J., Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D., Boerwinkle, Eric, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, Hu, Frank B., Demirkan, Ayse, Oostra, Ben A., de Andrade, Mariza, Turner, Stephen T., Ding, Jingzhong, Andrews, Jeanette S., Freedman, Barry I., Koenig, Wolfgang, Illig, Thomas, Doering, Angela, Wichmann, H. -Erich, Kolcic, Ivana, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E., Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H., Wright, Alan F., Campbell, Harry, Ellinghaus, David, Nothlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Endlich, Karlhans, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K., Nauck, Matthias, Stracke, Sylvia, Voelker, Uwe, Voelzke, Henry, Kovacs, Peter, Stumvoll, Michael, Magi, Reedik, Hofman, Albert, Uitterlinden, Andre G., Rivadeneira, Fernando, Aulchenko, Yurii S., Polasek, Ozren, Hastie, Nick, Vitart, Veronique, Helmer, Catherine, Wang, Jie Jin, Ruggiero, Daniela, Bergmann, Sven, Kaehoenen, Mika, Viikari, Jorma, Nikopensius, Tiit, Province, Michael, Ketkar, Shamika, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Giulianini, Franco, Kraemer, Bernhard K., Portas, Laura, Ford, Ian, Buckley, Brendan M., Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Sala, Cinzia, Metzger, Marie, Mitchell, Paul, Ciullo, Marina, Kim, Stuart K., Vollenweider, Peter, Raitakari, Olli, Metspalu, Andres, Palmer, Colin, Gasparini, Paolo, Pirastu, Mario, Jukema, J. Wouter, Probst-Hensch, Nicole M., Kronenberg, Florian, Toniolo, Daniela, Gudnason, Vilmundur, Shuldiner, Alan R., Coresh, Josef, Schmidt, Reinhold, Ferrucci, Luigi, Siscovick, David S., van Duijn, Cornelia M., Borecki, Ingrid, Kardia, Sharon L. R., Liu, Yongmei, Curhan, Gary C., Rudan, Igor, Gyllensten, Ulf, Wilson, James F., Franke, Andre, Pramstaller, Peter P., Rettig, Rainer, Prokopenko, Inga, Witteman, Jacqueline C. M., Hayward, Caroline, Ridker, Paul, Parsa, Afshin, Bochud, Murielle, Heid, Iris M., Goessling, Wolfram, Chasman, Daniel I., Kao, W. H. Linda, Fox, Caroline S., Pattaro, Cristian, Koettgen, Anna, Teumer, Alexander, Garnaas, Maija, Boeger, Carsten A., Fuchsberger, Christian, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C., O'Seaghdha, Conall M., Glazer, Nicole, Isaacs, Aaron, Liu, Ching-Ti, Smith, Albert V., O'Connell, Jeffrey R., Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Johnson, Andrew D., Gierman, Hinco J., Feitosa, Mary, Hwang, Shih-Jen, Atkinson, Elizabeth J., Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa, Toenjes, Anke, Dehghan, Abbas, Chouraki, Vincent, Holliday, Elizabeth G., Sorice, Rossella, Kutalik, Zoltan, Lehtimaeki, Terho, Esko, Tonu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y., Murgia, Federico, Trompet, Stella, Imboden, Medea, Kollerits, Barbara, Pistis, Giorgio, Harris, Tamara B., Launer, Lenore J., Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D., Boerwinkle, Eric, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, Hu, Frank B., Demirkan, Ayse, Oostra, Ben A., de Andrade, Mariza, Turner, Stephen T., Ding, Jingzhong, Andrews, Jeanette S., Freedman, Barry I., Koenig, Wolfgang, Illig, Thomas, Doering, Angela, Wichmann, H. -Erich, Kolcic, Ivana, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E., Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H., Wright, Alan F., Campbell, Harry, Ellinghaus, David, Nothlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Endlich, Karlhans, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K., Nauck, Matthias, Stracke, Sylvia, Voelker, Uwe, Voelzke, Henry, Kovacs, Peter, Stumvoll, Michael, Magi, Reedik, Hofman, Albert, Uitterlinden, Andre G., Rivadeneira, Fernando, Aulchenko, Yurii S., Polasek, Ozren, Hastie, Nick, Vitart, Veronique, Helmer, Catherine, Wang, Jie Jin, Ruggiero, Daniela, Bergmann, Sven, Kaehoenen, Mika, Viikari, Jorma, Nikopensius, Tiit, Province, Michael, Ketkar, Shamika, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Giulianini, Franco, Kraemer, Bernhard K., Portas, Laura, Ford, Ian, Buckley, Brendan M., Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Sala, Cinzia, Metzger, Marie, Mitchell, Paul, Ciullo, Marina, Kim, Stuart K., Vollenweider, Peter, Raitakari, Olli, Metspalu, Andres, Palmer, Colin, Gasparini, Paolo, Pirastu, Mario, Jukema, J. Wouter, Probst-Hensch, Nicole M., Kronenberg, Florian, Toniolo, Daniela, Gudnason, Vilmundur, Shuldiner, Alan R., Coresh, Josef, Schmidt, Reinhold, Ferrucci, Luigi, Siscovick, David S., van Duijn, Cornelia M., Borecki, Ingrid, Kardia, Sharon L. R., Liu, Yongmei, Curhan, Gary C., Rudan, Igor, Gyllensten, Ulf, Wilson, James F., Franke, Andre, Pramstaller, Peter P., Rettig, Rainer, Prokopenko, Inga, Witteman, Jacqueline C. M., Hayward, Caroline, Ridker, Paul, Parsa, Afshin, Bochud, Murielle, Heid, Iris M., Goessling, Wolfram, Chasman, Daniel I., Kao, W. H. Linda, and Fox, Caroline S.
- Abstract
Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
- Published
- 2012
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22. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
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Chasman, Daniel I., Fuchsberger, Christian, Pattaro, Cristian, Teumer, Alexander, Boeger, Carsten A., Endlich, Karlhans, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C., O'Seaghdha, Conall M., Glazer, Nicole, Isaacs, Aaron, Liu, Ching-Ti, Smith, Albert V., O'Connell, Jeffrey R., Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Johnson, Andrew D., Gierman, Hinco J., Feitosa, Mary F., Hwang, Shih-Jen, Atkinson, Elizabeth J., Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa, Toenjes, Anke, Dehghan, Abbas, Lambert, Jean-Charles, Holliday, Elizabeth G., Sorice, Rossella, Kutalik, Zoltan, Lehtimaeki, Terho, Esko, Tonu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y., Murgia, Federico, Trompet, Stella, Imboden, Medea, Coassin, Stefan, Pistis, Giorgio, Harris, Tamara B., Launer, Lenore J., Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D., Boerwinkle, Eric, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, Hu, Frank, Demirkan, Ayse, Oostra, Ben A., de Andrade, Mariza, Turner, Stephen T., Ding, Jingzhong, Andrews, Jeanette S., Freedman, Barry I., Giulianini, Franco, Koenig, Wolfgang, Illig, Thomas, Meisinger, Christa, Gieger, Christian, Zgaga, Lina, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E., Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H., Wright, Alan F., Campbell, Harry, Ellinghaus, David, Noethlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K., Nauck, Matthias, Stracke, Sylvia, Voelker, Uwe, Voelzke, Henry, Kovacs, Peter, Stumvoll, Michael, Maegi, Reedik, Hofman, Albert, Uitterlinden, Andre G., Rivadeneira, Fernando, Aulchenko, Yurii S., Polasek, Ozren, Hastie, Nick, Vitart, Veronique, Helmer, Catherine, Wang, Jie Jin, Stengel, Benedicte, Ruggiero, Daniela, Bergmann, Sven, Kahonen, Mika, Viikari, Jorma, Nikopensius, Tiit, Province, Michael, Ketkar, Shamika, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Kraemer, Bernhard K., Portas, Laura, Ford, Ian, Buckley, Brendan M., Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Sala, Cinzia, Mitchell, Paul, Ciullo, Marina, Kim, Stuart K., Vollenweider, Peter, Raitakari, Olli, Metspalu, Andres, Palmer, Colin, Gasparini, Paolo, Pirastu, Mario, Jukema, J. Wouter, Probst-Hensch, Nicole M., Kronenberg, Florian, Toniolo, Daniela, Gudnason, Vilmundur, Shuldiner, Alan R., Coresh, Josef, Schmidt, Reinhold, Ferrucci, Luigi, Siscovick, David S., van Duijn, Cornelia M., Borecki, Ingrid B., Kardia, Sharon L. R., Liu, Yongmei, Curhan, Gary C., Rudan, Igor, Gyllensten, Ulf, Wilson, James F., Franke, Andre, Pramstaller, Peter P., Rettig, Rainer, Prokopenko, Inga, Witteman, Jacqueline, Hayward, Caroline, Ridker, Paul M., Parsa, Afshin, Bochud, Murielle, Heid, Iris M., Kao, W. H. Linda, Fox, Caroline S., Koettgen, Anna, Chasman, Daniel I., Fuchsberger, Christian, Pattaro, Cristian, Teumer, Alexander, Boeger, Carsten A., Endlich, Karlhans, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C., O'Seaghdha, Conall M., Glazer, Nicole, Isaacs, Aaron, Liu, Ching-Ti, Smith, Albert V., O'Connell, Jeffrey R., Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Johnson, Andrew D., Gierman, Hinco J., Feitosa, Mary F., Hwang, Shih-Jen, Atkinson, Elizabeth J., Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa, Toenjes, Anke, Dehghan, Abbas, Lambert, Jean-Charles, Holliday, Elizabeth G., Sorice, Rossella, Kutalik, Zoltan, Lehtimaeki, Terho, Esko, Tonu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y., Murgia, Federico, Trompet, Stella, Imboden, Medea, Coassin, Stefan, Pistis, Giorgio, Harris, Tamara B., Launer, Lenore J., Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D., Boerwinkle, Eric, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, Hu, Frank, Demirkan, Ayse, Oostra, Ben A., de Andrade, Mariza, Turner, Stephen T., Ding, Jingzhong, Andrews, Jeanette S., Freedman, Barry I., Giulianini, Franco, Koenig, Wolfgang, Illig, Thomas, Meisinger, Christa, Gieger, Christian, Zgaga, Lina, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E., Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H., Wright, Alan F., Campbell, Harry, Ellinghaus, David, Noethlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K., Nauck, Matthias, Stracke, Sylvia, Voelker, Uwe, Voelzke, Henry, Kovacs, Peter, Stumvoll, Michael, Maegi, Reedik, Hofman, Albert, Uitterlinden, Andre G., Rivadeneira, Fernando, Aulchenko, Yurii S., Polasek, Ozren, Hastie, Nick, Vitart, Veronique, Helmer, Catherine, Wang, Jie Jin, Stengel, Benedicte, Ruggiero, Daniela, Bergmann, Sven, Kahonen, Mika, Viikari, Jorma, Nikopensius, Tiit, Province, Michael, Ketkar, Shamika, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Kraemer, Bernhard K., Portas, Laura, Ford, Ian, Buckley, Brendan M., Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Sala, Cinzia, Mitchell, Paul, Ciullo, Marina, Kim, Stuart K., Vollenweider, Peter, Raitakari, Olli, Metspalu, Andres, Palmer, Colin, Gasparini, Paolo, Pirastu, Mario, Jukema, J. Wouter, Probst-Hensch, Nicole M., Kronenberg, Florian, Toniolo, Daniela, Gudnason, Vilmundur, Shuldiner, Alan R., Coresh, Josef, Schmidt, Reinhold, Ferrucci, Luigi, Siscovick, David S., van Duijn, Cornelia M., Borecki, Ingrid B., Kardia, Sharon L. R., Liu, Yongmei, Curhan, Gary C., Rudan, Igor, Gyllensten, Ulf, Wilson, James F., Franke, Andre, Pramstaller, Peter P., Rettig, Rainer, Prokopenko, Inga, Witteman, Jacqueline, Hayward, Caroline, Ridker, Paul M., Parsa, Afshin, Bochud, Murielle, Heid, Iris M., Kao, W. H. Linda, Fox, Caroline S., and Koettgen, Anna
- Abstract
In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
- Published
- 2012
- Full Text
- View/download PDF
23. CUBN Is a Gene Locus for Albuminuria
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Boeger, Carsten A., Chen, Ming-Huei, Tin, Adrienne, Olden, Matthias, Koettgen, Anna, de Boer, Ian H., Fuchsberger, Christian, O'Seaghdha, Conall M., Pattaro, Cristian, Teumer, Alexander, Liu, Ching-Ti, Glazer, Nicole L., Li, Man, O'Conne, Jeffrey R., Tanaka, Toshiko, Peralta, Carmen A., Kutalik, Zoltan, Luan, Jian'an, Zhao, Jing Hua, Hwang, Shih-Jen, Akylbekova, Ermeg, Kramer, Holly, van der Harst, Pim, Smith, Albert V., Lohman, Kurt, de Andrade, Mariza, Hayward, Caroline, Kollerits, Barbara, Toenjes, Anke, Aspelund, Thor, Ingelsson, Erik, Eiriksdottir, Gudny, Launer, Lenore J., Harris, Tamara B., Shuldiner, Alan R., Mitchell, Braxton D., Arking, Dan E., Franceschini, Nora, Boerwinkle, Eric, Egan, Josephine, Hernandez, Dena, Reilly, Muredach, Townsend, Raymond R., Lumley, Thomas, Siscovick, David S., Psaty, Bruce M., Kestenbaum, Bryan, Haritunians, Talin, Bergmann, Sven, Vollenweider, Peter, Waeber, Gerard, Mooser, Vincent, Waterworth, Dawn, Johnson, Andrew D., Florez, Jose C., Meigs, James B., Lu, Xiaoning, Turner, Stephen T., Atkinson, Elizabeth J., Leak, Tennille S., Aasarod, Knut, Skorpen, Frank, Syvänen, Ann-Christine, Illig, Thomas, Baumert, Jens, Koenig, Wolfgang, Kraemer, Bernhard K., Devuyst, Olivier, Mychaleckyj, Josyf C., Minelli, Cosetta, Bakker, Stephan J. L., Kedenko, Lyudmyla, Paulweber, Bernhard, Coassin, Stefan, Endlich, Karlhans, Kroemer, Heyo K., Biffar, Reiner, Stracke, Sylvia, Voelzke, Henry, Stumvol, Michael, Maegi, Reedik, Campbell, Harry, Vitart, Veronique, Hastie, Nicholas D., Gudnason, Vilmundur, Kardia, Sharon L. R., Liu, Yongmei, Polasek, Ozren, Curhan, Gary, Kronenberg, Florian, Prokopenko, Inga, Rudan, Igor, Ärnlöv, Johan, Hallan, Stein, Navis, Gerjan, Parsa, Afshin, Ferrucci, Luigi, Coresh, Josef, Shlipak, Michael G., Bul, Shelley B., Paterson, Andrew D., Wichmann, H. -Erich, Wareham, Nicholas J., Loos, Ruth J. F., Rotter, Jerome I., Pramstaller, Peter P., Cupples, L. Adrienne, Beckmann, Jacques S., Yang, Qiong, Heid, Iris M., Rettig, Rainer, Dreisbach, Albert W., Bochud, Murielle, Fox, Caroline S., Kao, W. H. L., Boeger, Carsten A., Chen, Ming-Huei, Tin, Adrienne, Olden, Matthias, Koettgen, Anna, de Boer, Ian H., Fuchsberger, Christian, O'Seaghdha, Conall M., Pattaro, Cristian, Teumer, Alexander, Liu, Ching-Ti, Glazer, Nicole L., Li, Man, O'Conne, Jeffrey R., Tanaka, Toshiko, Peralta, Carmen A., Kutalik, Zoltan, Luan, Jian'an, Zhao, Jing Hua, Hwang, Shih-Jen, Akylbekova, Ermeg, Kramer, Holly, van der Harst, Pim, Smith, Albert V., Lohman, Kurt, de Andrade, Mariza, Hayward, Caroline, Kollerits, Barbara, Toenjes, Anke, Aspelund, Thor, Ingelsson, Erik, Eiriksdottir, Gudny, Launer, Lenore J., Harris, Tamara B., Shuldiner, Alan R., Mitchell, Braxton D., Arking, Dan E., Franceschini, Nora, Boerwinkle, Eric, Egan, Josephine, Hernandez, Dena, Reilly, Muredach, Townsend, Raymond R., Lumley, Thomas, Siscovick, David S., Psaty, Bruce M., Kestenbaum, Bryan, Haritunians, Talin, Bergmann, Sven, Vollenweider, Peter, Waeber, Gerard, Mooser, Vincent, Waterworth, Dawn, Johnson, Andrew D., Florez, Jose C., Meigs, James B., Lu, Xiaoning, Turner, Stephen T., Atkinson, Elizabeth J., Leak, Tennille S., Aasarod, Knut, Skorpen, Frank, Syvänen, Ann-Christine, Illig, Thomas, Baumert, Jens, Koenig, Wolfgang, Kraemer, Bernhard K., Devuyst, Olivier, Mychaleckyj, Josyf C., Minelli, Cosetta, Bakker, Stephan J. L., Kedenko, Lyudmyla, Paulweber, Bernhard, Coassin, Stefan, Endlich, Karlhans, Kroemer, Heyo K., Biffar, Reiner, Stracke, Sylvia, Voelzke, Henry, Stumvol, Michael, Maegi, Reedik, Campbell, Harry, Vitart, Veronique, Hastie, Nicholas D., Gudnason, Vilmundur, Kardia, Sharon L. R., Liu, Yongmei, Polasek, Ozren, Curhan, Gary, Kronenberg, Florian, Prokopenko, Inga, Rudan, Igor, Ärnlöv, Johan, Hallan, Stein, Navis, Gerjan, Parsa, Afshin, Ferrucci, Luigi, Coresh, Josef, Shlipak, Michael G., Bul, Shelley B., Paterson, Andrew D., Wichmann, H. -Erich, Wareham, Nicholas J., Loos, Ruth J. F., Rotter, Jerome I., Pramstaller, Peter P., Cupples, L. Adrienne, Beckmann, Jacques S., Yang, Qiong, Heid, Iris M., Rettig, Rainer, Dreisbach, Albert W., Bochud, Murielle, Fox, Caroline S., and Kao, W. H. L.
- Abstract
Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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- 2011
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24. Transplant survival: knowing the future
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Hutchinson, James A and Böger, Carsten A
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- 2016
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25. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity
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Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Goncalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Heijer, Martin, den Hollander, Anneke I, den Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Edwards, Todd L, Ellinghaus, David, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D, Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franco, Oscar H, Franke, Andre, Franks, Paul W, Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P, Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan FA, Grarup, Niels, Griffiths, Helen L, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Have, Christian T, Hayward, Caroline, He, Liang, Heard-Costa, Nancy L, Heath, Andrew C, Heid, Iris M, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna MM, Hu, Yao, Huang, Paul L, Huffman, Jennifer E, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A, Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S, Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lamparter, David, Lange, Ethan M, Lange, Leslie A, Langenberg, Claudia, Larson, Eric B, Lee, Nanette R, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J, Liu, Yongmei, Lo, Ken Sin, Lophatananon, Artitaya, Lotery, Andrew J, Loukola, Anu, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L, McCarthy, Mark I, McKean-Cowdin, Roberta, Medland, Sarah E, Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L, Moilanen, Leena, Moitry, Marie, Montgomery, Grant W, Mook-Kanamori, Dennis O, Moore, Carmel, Mori, Trevor A, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Narisu, Narisu, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Nyholt, Dale R, O'Connel, Jeffrey R, O’Donoghue, Michelle L., Olde Loohuis, Loes M, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Palmer, Nicholette D, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John RB, Pers, Tune H, Person, Thomas N, Peters, Annette, Petersen, Eva RB, Peyser, Patricia A, Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J, Puolijoki, Hannu, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Renström, Frida, Rheinberger, Myriam, Ridker, Paul M, Rioux, John D, Rivas, Manuel A, Roberts, David J, Robertson, Neil R, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati H, Sheu, Wayne H-H, Sim, Xueling, Slater, Andrew J, Small, Kerrin S, Smith, Albert Vernon, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E, Strauch, Konstantin, Stringham, Heather M, Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J, Tada, Hayato, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Uusitupa, Matti, van der Laan, Sander W, van Duijn, Cornelia M, van Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Velez Edwards, Digna R, Vermeulen, Sita H, Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E, Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Ware, Erin B, Wareham, Nicholas J, Warren, Helen R, Waterworth, Dawn M, Wessel, Jennifer, White, Harvey D, Willer, Cristen J, Wilson, James G, Witte, Daniel R, Wood, Andrew R, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I, Pospisilik, John A, Rivadeneira, Fernando, Borecki, Ingrid B, Deloukas, Panos, Frayling, Timothy M, Lettre, Guillaume, North, Kari E, Lindgren, Cecilia M, Hirschhorn, Joel N, and Loos, Ruth JF
- Abstract
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, non-coding variants from which pinpointing causal genes remains challenging. Here, we combined data from 718,734 individuals to discover rare and low-frequency (MAF<5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which eight in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, ZNF169) newly implicated in human obesity, two (MC4R, KSR2) previously observed in extreme obesity, and two variants in GIPR. Effect sizes of rare variants are ~10 times larger than of common variants, with the largest effect observed in carriers of an MC4R stop-codon (p.Tyr35Ter, MAF=0.01%), weighing ~7kg more than non-carriers. Pathway analyses confirmed enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically-supported therapeutic targets to treat obesity.
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- 2018
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26. Adrenal Aldosterone Biosynthesis Is Elevated in a Model of Chronic Renal Failure – Role of Local Adrenal Renin-Angiotensin System
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Endemann, Dierk H., primary, Wolf, Konrad, additional, Boeger, Carsten A., additional, Riegger, Günter A.J., additional, and Krämer, Bernhard K., additional
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- 2004
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27. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function
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Gorski, Mathias, van der Most, Peter J., Teumer, Alexander, Chu, Audrey Y., Li, Man, Mijatovic, Vladan, Nolte, Ilja M., Cocca, Massimiliano, Taliun, Daniel, Gomez, Felicia, Li, Yong, Tayo, Bamidele, Tin, Adrienne, Feitosa, Mary F., Aspelund, Thor, Attia, John, Biffar, Reiner, Bochud, Murielle, Boerwinkle, Eric, Borecki, Ingrid, Bottinger, Erwin P., Chen, Ming-Huei, Chouraki, Vincent, Ciullo, Marina, Coresh, Josef, Cornelis, Marilyn C., Curhan, Gary C., d’Adamo, Adamo Pio, Dehghan, Abbas, Dengler, Laura, Ding, Jingzhong, Eiriksdottir, Gudny, Endlich, Karlhans, Enroth, Stefan, Esko, Tõnu, Franco, Oscar H., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hancock, Stephen J., Harris, Tamara B., Helmer, Catherine, Höllerer, Simon, Hofer, Edith, Hofman, Albert, Holliday, Elizabeth G., Homuth, Georg, Hu, Frank B., Huth, Cornelia, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Imboden, Medea, Johansson, Åsa, Kähönen, Mika, König, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kumar, Ashish, Kutalik, Zoltan, Lambert, Jean-Charles, Launer, Lenore J., Lehtimäki, Terho, de Borst, Martin, Navis, Gerjan, Swertz, Morris, Liu, Yongmei, Lohman, Kurt, Loos, Ruth J. F., Lu, Yingchang, Lyytikäinen, Leo-Pekka, McEvoy, Mark A., Meisinger, Christa, Meitinger, Thomas, Metspalu, Andres, Metzger, Marie, Mihailov, Evelin, Mitchell, Paul, Nauck, Matthias, Oldehinkel, Albertine J., Olden, Matthias, WJH Penninx, Brenda, Pistis, Giorgio, Pramstaller, Peter P., Probst-Hensch, Nicole, Raitakari, Olli T., Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando, Robino, Antonietta, Rosas, Sylvia E., Ruderfer, Douglas, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia, Schmidt, Helena, Schmidt, Reinhold, Scott, Rodney J., Sedaghat, Sanaz, Smith, Albert V., Sorice, Rossella, Stengel, Benedicte, Stracke, Sylvia, Strauch, Konstantin, Toniolo, Daniela, Uitterlinden, Andre G., Ulivi, Sheila, Viikari, Jorma S., Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Vuckovic, Dragana, Waldenberger, Melanie, Jin Wang, Jie, Yang, Qiong, Chasman, Daniel I., Tromp, Gerard, Snieder, Harold, Heid, Iris M., Fox, Caroline S., Köttgen, Anna, Pattaro, Cristian, Böger, Carsten A., and Fuchsberger, Christian
- Abstract
HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.
- Published
- 2017
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28. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
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Justice, Anne E., Winkler, Thomas W., Feitosa, Mary F., Graff, Misa, Fisher, Virginia A., Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S., Ahluwalia, Tarunveer S., Chu, Audrey Y., Heard-Costa, Nancy L., Lim, Elise, Perez, Jeremiah, Eicher, John D., Kutalik, Zoltán, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F., Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E., Jackson, Anne U., Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E., Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P. S., Müller-Nurasyid, Martina, Navarro, Pau, Pérusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A., Stančáková, Alena, Strawbridge, Rona J., Stringham, Heather M., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vedantam, Sailaja L., Verweij, Niek, Vink, Jacqueline M., Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E., Zubair, Niha, Abecasis, Gonçalo R., Adair, Linda S., Afaq, Saima, Afzal, Uzma, Bakker, Stephan J. L., Bartz, Traci M., Beilby, John, Bergman, Richard N., Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L., Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M., Buyske, Steve, Campbell, Harry, Chambers, John C., Collins, Francis S., Curran, Joanne E., de Borst, Gert J., de Craen, Anton J. M., de Geus, Eco J. C., Dedoussis, George, Delgado, Graciela E., den Ruijter, Hester M., Eiriksdottir, Gudny, Eriksson, Anna L., Esko, Tõnu, Faul, Jessica D., Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kähönen, Nina, Ingelsson, Erik, James, Alan L., Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A., Jørgensen, Marit E., Juonala, Markus, Kähönen, Mika, Karlsson, Magnus, Koistinen, Heikki A., Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Krämer, Bernhard K., Kuusisto, Johanna, Kvaløy, Kirsti, Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lee, Nanette R., Lind, Lars, Lindgren, Cecilia M., Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A. F., Männikkö, Reija, Marques-Vidal, Pedro, Martin, Nicholas G., McKenzie, Colin A., McKnight, Barbara, Mellström, Dan, Menni, Cristina, Montgomery, Grant W., Musk, AW (Bill), Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Peyser, Patricia A., Pisinger, Charlotta, Porteous, David J., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rasmussen-Torvik, Laura J., Rawal, Rajesh, Rice, Treva, Ridker, Paul M., Rose, Lynda M., Bien, Stephanie A., Rudan, Igor, Sanna, Serena, Sarzynski, Mark A., Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A., Sennblad, Bengt, Siemelink, Marten A., Silbernagel, Günther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A., Stott, David J., Swertz, Morris A., Swift, Amy J., Taylor, Kent D., Tayo, Bamidele O., Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G., Vandenput, Liesbeth, Vohl, Marie-Claude, Völzke, Henry, Vonk, Judith M., Waeber, Gérard, Waldenberger, Melanie, Westendorp, R. G. J., Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H. R., Wong, Andrew, Wright, Alan F., Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Böger, Carsten A., Boomsma, Dorret I., Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I., Chen, Yii-DerIda, Chines, Peter S., Cooper, Richard S., Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans- Jörgen, Gudnason, Vilmundur, Haiman, Christopher A., Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D., Wouter Jukema, J, Kardia, Sharon L. R., Kivimaki, Mika, Kooner, Jaspal S., Kuh, Diana, Laakso, Markku, Lehtimäki, Terho, Marchand, Loic Le, März, Winfried, McCarthy, Mark I., Metspalu, Andres, Morris, Andrew P., Ohlsson, Claes, Palmer, Lyle J., Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Smith, Blair H., Sørensen, Thorkild I. A., Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J., Weir, David R., Whitfield, John B., Wilson, James F., Tyrrell, Jessica, Frayling, Timothy M., Barroso, Inês, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S., Hirschhorn, Joel N., Hunter, David J., Spector, Tim D., Strachan, David P., van Duijn, Cornelia M., Heid, Iris M., Mohlke, Karen L., Marchini, Jonathan, Loos, Ruth J. F., Kilpeläinen, Tuomas O., Liu, Ching-Ti, Borecki, Ingrid B., North, Kari E., and Cupples, L Adrienne
- Abstract
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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- 2017
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29. Do We Need to Check Our Genes for a Correct Estimate of GFR?
- Author
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Böger, Carsten A.
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- 2014
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30. Rare and low-frequency coding variants alter human adult height
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Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J., de Denus, Simon, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D, Feitosa, Mary F, Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D, Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, He, Liang, Heid, Iris M, Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Hovingh, G. Kees, Howson, Joanna MM, Hoyng, Carel B, Huang, Paul L, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jhun, Min A, Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jousilahti, Pekka, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A, Kitajima, Hidetoshi, Kluivers, Kirsten B, Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A, Lange, Ethan M, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Larson, Eric B, Lee, I-Te, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Mackey, David A, Madden, Pamela AF, Manning, Alisa K, Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G, Mazul, Angela L, Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L, Mook-Kanamori, Dennis O, Morgan, Anna, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Ntalla, Ioanna, O'Connel, Jeffrey R, Oksa, Heikki, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John R.B., Person, Thomas N, Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renström, Frida, Ridker, Paul M, Rioux, John D, Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert Vernon, Smith, Jennifer A, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Steinthorsdottir, Valgerdur, Stringham, Heather M, Stumvoll, Michael, Surendran, Praveen, Hart, Leen M ‘t, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Ulivi, Sheila, van der Laan, Sander W, Van Der Leij, Andries R, van Duijn, Cornelia M, van Schoor, Natasja M, van Setten, Jessica, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J, Warren, Helen R, Wessel, Jennifer, Willems, Sara M, Wilson, James G, Witte, Daniel R, Woods, Michael O, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I, Willer, Cristen J, Stefansson, Kari, Borecki, Ingrid B, Liu, Dajiang J, North, Kari E, Heard-Costa, Nancy L, Pers, Tune H, Lindgren, Cecilia M, Oxvig, Claus, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth JF, Frayling, Timothy M, Hirschhorn, Joel N, Deloukas, Panos, and Lettre, Guillaume
- Abstract
Summary Height is a highly heritable, classic polygenic trait with ∼700 common associated variants identified so far through genome-wide association studies. Here, we report 83 height-associated coding variants with lower minor allele frequencies (range of 0.1-4.8%) and effects of up to 2 cm/allele (e.g. in IHH, STC2, AR and CRISPLD2), >10 times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (+1-2 cm/allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
- Published
- 2016
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31. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
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Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y., Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H., Johnson, Andrew D., Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F., Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B., Nolte, Ilja M., van der Most, Peter J., Wright, Alan F., Shuldiner, Alan R., Morrison, Alanna C., Hofman, Albert, Smith, Albert V., Dreisbach, Albert W., Franke, Andre, Uitterlinden, Andre G., Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I., Ponte, Belen, Oostra, Ben A., Paulweber, Bernhard, Krämer, Bernhard K., Mitchell, Braxton D., Buckley, Brendan M., Peralta, Carmen A., Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N., Shaffer, Christian M., Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M., Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S., Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J., Holliday, Elizabeth G., Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B., Navis, Gerjan J., Curhan, Gary C., Ehret, George B., Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W., Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K., Kramer, Holly, Lin, Honghuang, Leach, I. Mateo, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M., Kolcic, Ivana, Persico, Ivana, Jukema, J. Wouter, Wilson, James F., Felix, Janine F., Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M., Gaspoz, Jean-Michel, Smith, Jennifer A., Faul, Jessica D., Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N., Attia, John, Whitfield, John B., Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C., Karjalainen, Juha, Fernandes, Jyotika K., Endlich, Karlhans, Butterbach, Katja, Keene, Keith L., Lohman, Kurt, Portas, Laura, Launer, Lenore J., Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M., Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E., Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C., Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A., Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K., Sale, Michele M., Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G., Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H., Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B., Ridker, Paul M., Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H., Abecasis, Goncalo R., Adair, Linda S., Alexander, Myriam, Altshuler, David, Amin, Najaf, Arking, Dan E., Arora, Pankaj, Aulchenko, Yurii, Bakker, Stephan J. L., Bandinelli, Stefania, Barroso, Ines, Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Bis, Joshua C., Boehnke, Michael, Bonnycastle, Lori L., Bornstein, Stefan R., Bots, Michiel L., Bragg-Gresham, Jennifer L., Brand, Stefan-Martin, Brand, Eva, Braund, Peter S., Brown, Morris J., Burton, Paul R., Casas, Juan P., Caulfield, Mark J., Chakravarti, Aravinda, Chambers, John C., Chandak, Giriraj R., Chang, Yen-Pei C., Charchar, Fadi J., Chaturvedi, Nish, Shin Cho, Yoon, Clarke, Robert, Collins, Francis S., Collins, Rory, Connell, John M., Cooper, Jackie A., Cooper, Matthew N., Cooper, Richard S., Corsi, Anna Maria, Dörr, Marcus, Dahgam, Santosh, Danesh, John, Smith, George Davey, Day, Ian N. M., Deloukas, Panos, Denniff, Matthew, Dominiczak, Anna F., Dong, Yanbin, Doumatey, Ayo, Elliott, Paul, Elosua, Roberto, Erdmann, Jeanette, Eyheramendy, Susana, Farrall, Martin, Fava, Cristiano, Forrester, Terrence, Fowkes, F. Gerald R., Fox, Ervin R., Frayling, Timothy M., Galan, Pilar, Ganesh, Santhi K., Garcia, Melissa, Gaunt, Tom R., Glazer, Nicole L., Go, Min Jin, Goel, Anuj, Grässler, Jürgen, Grobbee, Diederick E., Groop, Leif, Guarrera, Simonetta, Guo, Xiuqing, Hadley, David, Hamsten, Anders, Han, Bok-Ghee, Hardy, Rebecca, Hartikainen, Anna-Liisa, Heath, Simon, Heckbert, Susan R., Hedblad, Bo, Hercberg, Serge, Hernandez, Dena, Hicks, Andrew A., Hilton, Gina, Hingorani, Aroon D., Bolton, Judith A Hoffman, Hopewell, Jemma C., Howard, Philip, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Ikram, M. Arfan, Islam, Muhammad, Iwai, Naoharu, Jarvelin, Marjo-Riitta, Jackson, Anne U., Jafar, Tazeen H., Janipalli, Charles S., Johnson, Toby, Kathiresan, Sekar, Khaw, Kay-Tee, Kim, Hyung-Lae, Kinra, Sanjay, Kita, Yoshikuni, Kivimaki, Mika, Kooner, Jaspal S., Kumar, M. J. Kranthi, Kuh, Diana, Kulkarni, Smita R., Kumari, Meena, Kuusisto, Johanna, Kuznetsova, Tatiana, Laakso, Markku, Laan, Maris, Laitinen, Jaana, Lakatta, Edward G., Langefeld, Carl D., Larson, Martin G., Lathrop, Mark, Lawlor, Debbie A., Lawrence, Robert W., Lee, Jong-Young, Lee, Nanette R., Levy, Daniel, Li, Yali, Longstreth, Will T., Luan, Jian'an, Lucas, Gavin, Ludwig, Barbara, Mangino, Massimo, Mani, K. Radha, Marmot, Michael G., Mattace-Raso, Francesco U. S., Matullo, Giuseppe, McArdle, Wendy L., McKenzie, Colin A., Meitinger, Thomas, Melander, Olle, Meneton, Pierre, Meschia, James F., Miki, Tetsuro, Milaneschi, Yuri, Mohlke, Karen L., Mooser, Vincent, Morken, Mario A., Morris, Richard W., Mosley, Thomas H., Najjar, Samer, Narisu, Narisu, Newton-Cheh, Christopher, Nguyen, Khanh-Dung Hoang, Nilsson, Peter, Nyberg, Fredrik, O'Donnell, Christopher J., Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ong, RickTwee-Hee, Ongen, Halit, Onland-Moret, N. Charlotte, O'Reilly, Paul F., Org, Elin, Orru, Marco, Palmas, Walter, Palmen, Jutta, Palmer, Lyle J., Palmer, Nicholette D., Parker, Alex N., Peden, John F., Peltonen, Leena, Perola, Markus, Pihur, Vasyl, Platou, Carl G. P., Plump, Andrew, Prabhakaran, Dorairajan, Psaty, Bruce M., Raffel, Leslie J., Rao, Dabeeru C., Rasheed, Asif, Ricceri, Fulvio, Rice, Kenneth M., Rosengren, Annika, Rotter, Jerome I., Rudock, Megan E., Sõber, Siim, Salako, Tunde, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schwartz, Steven M., Schwarz, Peter E. H., Scott, Laura J., Scott, James, Scuteri, Angelo, Sehmi, Joban S., Seielstad, Mark, Seshadri, Sudha, Sharma, Pankaj, Shaw-Hawkins, Sue, Shi, Gang, Shrine, Nick R. G., Sijbrands, Eric J. G., Sim, Xueling, Singleton, Andrew, Sjögren, Marketa, Smith, Nicholas L., Artigas, Maria Soler, Spector, Tim D., Staessen, Jan A., Stancakova, Alena, Steinle, Nanette I., Strachan, David P., Stringham, Heather M., Sun, Yan V., Swift, Amy J., Tabara, Yasuharu, Tai, E-Shyong, Talmud, Philippa J., Taylor, Andrew, Terzic, Janos, Thelle, Dag S., Tobin, Martin D., Tomaszewski, Maciej, Tripathy, Vikal, Tuomilehto, Jaakko, Tzoulaki, Ioanna, Uda, Manuela, Ueshima, Hirotsugu, Uiterwaal, Cuno S. P. M., Umemura, Satoshi, van der Harst, Pim, van der Schouw, Yvonne T., van Gilst, Wiek H., Vartiainen, Erkki, Vasan, Ramachandran S., Veldre, Gudrun, Verwoert, Germaine C., Viigimaa, Margus, Vinay, D. G., Vineis, Paolo, Voight, Benjamin F., Vollenweider, Peter, Wagenknecht, Lynne E., Wain, Louise V., Wang, Xiaoling, Wang, Thomas J., Wareham, Nicholas J., Watkins, Hugh, Weder, Alan B., Whincup, Peter H., Wiggins, Kerri L., Witteman, Jacqueline C. M., Wong, Andrew, Wu, Ying, Yajnik, Chittaranjan S., Yao, Jie, Young, J. H., Zelenika, Diana, Zhai, Guangju, Zhang, Weihua, Zhang, Feng, Zhao, Jing Hua, Zhu, Haidong, Zhu, Xiaofeng, Zitting, Paavo, Zukowska-Szczechowska, Ewa, Okada, Yukinori, Wu, Jer-Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su-Chi, Wong, Tien-Yin, Liu, Jianjun, Young, Terri L., Aung, Tin, Teo, Yik-Ying, Kim, Young Jin, Kang, Daehee, Chen, Chien-Hsiun, Tsai, Fuu-Jen, Chang, Li-Ching, Fann, S. -J. Cathy, Mei, Hao, Hixson, James E., Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan-Tsong, Tanaka, Toshihiro, Reilly, Muredach P, Schunkert, Heribert, Assimes, Themistocles L., Hall, Alistair, Hengstenberg, Christian, König, Inke R., Laaksonen, Reijo, McPherson, Ruth, Thompson, John R., Thorsteinsdottir, Unnur, Ziegler, Andreas, Absher, Devin, Chen, Li, Cupples13, L. Adrienne, Halperin, Eran, Li, Mingyao, Musunuru, Kiran, Preuss, Michael, Schillert, Arne, Thorleifsson, Gudmar, Wells, George A., Holm, Hilma, Roberts, Robert, Stewart, Alexandre F. R., Fortmann, Stephen, Go, Alan, Hlatky, Mark, Iribarren, Carlos, Knowles, Joshua, Myers, Richard, Quertermous, Thomas, Sidney, Steven, Risch, Neil, Tang, Hua, Blankenberg, Stefan, Schnabel, Renate, Sinning, Christoph, Lackner, Karl J., Tiret, Laurence, Nicaud, Viviane, Cambien, Francois, Bickel, Christoph, Rupprecht, Hans J., Perret, Claire, Proust, Carole, Münzel, Thomas F., Barbalic, Maja, Chen, Ida Yii-Der, Demissie-Banjaw, Serkalem, Folsom, Aaron, Lumley, Thomas, Marciante, Kristin, Taylor, Kent D., Volcik, Kelly, Gretarsdottir, Solveig, Gulcher, Jeffrey R., Kong, Augustine, Stefansson, Kari, Thorgeirsson, Gudmundur, Andersen, Karl, Fischer, Marcus, Grosshennig, Anika, Linsel-Nitschke, Patrick, Stark, Klaus, Schreiber, Stefan, Aherrahrou, Zouhair, Bruse, Petra, Doering, Angela, Klopp, Norman, Diemert, Patrick, Loley, Christina, Medack, Anja, Nahrstedt, Janja, Peters, Annette, Wagner, Arnika K., Willenborg, Christina, Böhm, Bernhard O., Dobnig, Harald, Grammer, Tanja B., Hoffmann, Michael M., Meinitzer, Andreas, Winkelmann, Bernhard R., Pilz, Stefan, Renner, Wilfried, Scharnagl, Hubert, Stojakovic, Tatjana, Tomaschitz, Andreas, Winkler, Karl, Guiducci, Candace, Burtt, Noel, Gabriel, Stacey B., Dandona, Sonny, Jarinova, Olga, Qu, Liming, Wilensky, Robert, Matthai, William, Hakonarson, Hakon H., Devaney, Joe, Burnett, Mary Susan, Pichard, Augusto D., Kent, Kenneth M., Satler, Lowell, Lindsay, Joseph M., Waksman, Ron, Knouff, Christopher W., Waterworth, Dawn M., Walker, Max C., Epstein, Stephen E., Rader, Daniel J., Nelson, Christopher P., Wright, Benjamin J., Balmforth, Anthony J., Ball, Stephen G., Loehr, Laura R., Rosamond, Wayne D., Benjamin, Emelia, Haritunians, Talin, Couper, David, Murabito, Joanne, Wang, Ying A., Stricker, Bruno H., Chang, Patricia P., Willerson, James T., Felix, Stephan B., Watzinger, Norbert, Aragam, Jayashri, Zweiker, Robert, Lind, Lars, Rodeheffer, Richard J., Greiser, Karin Halina, Deckers, Jaap W., Stritzke, Jan, Ingelsson, Erik, Kullo, Iftikhar, Haerting, Johannes, Reffelmann, Thorsten, Redfield, Margaret M., Werdan, Karl, Mitchell, Gary F., Arnett, Donna K., Gottdiener, John S., Blettner, Maria, Friedrich, Nele, Kovacs, Peter, Wild, Philipp S., Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P. S., Carroll, Robert J., Penninx, Brenda W., Scott, Rodney J., Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H., Kardia, Sharon L. R., Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J., Turner, Stephen T., Rosas, Sylvia E., Stracke, Sylvia, Harris, Tamara B., Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J. F., Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P., Parsa, Afshin, O'Connell, Jeffrey R., Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H., Böger, Carsten A., Goessling, Wolfram, Chasman, Daniel I., Köttgen, Anna, Kao, W. H. Linda, and Fox, Caroline S.
- Abstract
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
- Published
- 2016
- Full Text
- View/download PDF
32. Genome-wide association study of kidney function decline in individuals of European descent
- Author
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Gorski, Mathias, Tin, Adrienne, Garnaas, Maija, McMahon, Gearoid M., Chu, Audrey Y., Tayo, Bamidele O., Pattaro, Cristian, Teumer, Alexander, Chasman, Daniel I., Chalmers, John, Hamet, Pavel, Tremblay, Johanne, Woodward, Marc, Aspelund, Thor, Eiriksdottir, Gudny, Gudnason, Vilmundur, Harris, Tammara B., Launer, Lenore J., Smith, Albert V., Mitchell, Braxton D., O'Connell, Jeffrey R., Shuldiner, Alan R., Coresh, Josef, Li, Man, Freudenberger, Paul, Hofer, Edith, Schmidt, Helena, Schmidt, Reinhold, Holliday, Elizabeth G., Mitchell, Paul, Wang, Jie Jin, de Boer, Ian H., Li, Guo, Siscovick, David S., Kutalik, Zoltan, Corre, Tanguy, Vollenweider, Peter, Waeber, Gérard, Gupta, Jayanta, Kanetsky, Peter A., Hwang, Shih-Jen, Olden, Matthias, Yang, Qiong, de Andrade, Mariza, Atkinson, Elizabeth J., Kardia, Sharon L.R., Turner, Stephen T., Stafford, Jeanette M., Ding, Jingzhong, Liu, Yongmei, Barlassina, Cristina, Cusi, Daniele, Salvi, Erika, Staessen, Jan A, Ridker, Paul M, Grallert, Harald, Meisinger, Christa, Müller-Nurasyid, Martina, Krämer, Bernhard K., Kramer, Holly, Rosas, Sylvia E., Nolte, Ilja M., Penninx, Brenda W., Snieder, Harold, Del Greco, Fabiola, Franke, Andre, Nöthlings, Ute, Lieb, Wolfgang, Bakker, Stephan J.L., Gansevoort, Ron T., van der Harst, Pim, Dehghan, Abbas, Franco, Oscar H., Hofman, Albert, Rivadeneira, Fernando, Sedaghat, Sanaz, Uitterlinden, André G., Coassin, Stefan, Haun, Margot, Kollerits, Barbara, Kronenberg, Florian, Paulweber, Bernhard, Aumann, Nicole, Endlich, Karlhans, Pietzner, Mike, Völker, Uwe, Rettig, Rainer, Chouraki, Vincent, Helmer, Catherine, Lambert, Jean-Charles, Metzger, Marie, Stengel, Benedicte, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli, Johnson, Andrew, Parsa, Afshin, Bochud, Murielle, Heid, Iris M., Goessling, Wolfram, Köttgen, Anna, Kao, H. Linda, Fox, Caroline S., and Böger, Carsten A.
- Subjects
chronic kidney disease ,kidney development - Abstract
Genome wide association studies (GWAS) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, SNPs at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1 and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFRdecline of 3ml/min/1.73m2 or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11 and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 hours after gentamicin treatment compared to controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.
- Published
- 2014
- Full Text
- View/download PDF
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