المؤلفون: Kanoni, Stavroula, Graham, Sarah E, Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg JM, 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, Yousri, Noha A, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, 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, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E, Bradfield, Jonathan P, Ruotsalainen, Sanni E, Daw, EWarwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Vazquez-Moreno, Miguel, Feitosa, Mary F, Wojczynski, Mary K, Wang, Zhe, Preuss, Michael H, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Tsao, Noah L, Verma, Anurag, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Le, Phuong, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L, Marten, Jonathan, Frank, Mirjam, 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, Bayyana, Swati, Stringham, Heather M, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul RHJ, 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, Nardone, Giuseppe Giovanni, 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 RB, 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, Li, Xiaoyin, Liang, Jingjing, 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 HH, Ikram, M Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline WJ, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, 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, Kardia, Sharon LR, 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, Hollander, Anneke Iden, 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, DC, Arnett, Donna K, Hunt, Steven C, Walker, Mark, Koistinen, Heikki A, Chandak, Giriraj R, Mercader, Josep M, Costanzo, Maria C, Jang, Dongkeun, Burtt, Noël P, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, 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 NA, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M 't, Elders, Petra JM, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth JF, 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 FA, Kiemeney, Lambertus ALM, 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, van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P, Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, 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 KE, Boomsma, Dorret I, Willemsen, Allegonda HM, Cupples, LAdrienne, van Meurs, Joyce BJ, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, 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, YEugene, Ho, Yuk-Lam, Lynch, Julie A, Rader, Daniel J, Tsao, Philip S, Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J, Gaziano, John M, Wilson, Peter WF, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Mohlke, Karen L, Sun, Yan V, Morris, Andrew P, Boehnke, Michael, Brown, Christopher D, Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J, Assimes, Themistocles L, Peloso, Gina M

المصدر: essn: 1474-760X ; nlmid: 100960660

مصطلحات موضوعية: Cholesterol, GWAS, Genetics, Genome-wide association study, Lipids, Humans, Genetic Predisposition to Disease, Sex Characteristics, Phenotype, Polymorphism, Single Nucleotide, Genetic Pleiotropy

الوصف: BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

وصف الملف: application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/345879Test

الإتاحة: https://doi.org/10.17863/CAM.93301Test
https://www.repository.cam.ac.uk/handle/1810/345879Test

المؤلفون: Kanoni, Stavroula, Graham, Sarah E, Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg JM, 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, Yousri, Noha A, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, 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, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E, Bradfield, Jonathan P, Ruotsalainen, Sanni E, Daw, EWarwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Vazquez-Moreno, Miguel, Feitosa, Mary F, Wojczynski, Mary K, Wang, Zhe, Preuss, Michael H, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Tsao, Noah L, Verma, Anurag, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Le, Phuong, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L, Marten, Jonathan, Frank, Mirjam, 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, Bayyana, Swati, Stringham, Heather M, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul RHJ, 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, Nardone, Giuseppe Giovanni, 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 RB, 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, Li, Xiaoyin, Liang, Jingjing, 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 HH, Ikram, M Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline WJ, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, 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, Kardia, Sharon LR, 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, Hollander, Anneke Iden, 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, DC, Arnett, Donna K, Hunt, Steven C, Walker, Mark, Koistinen, Heikki A, Chandak, Giriraj R, Mercader, Josep M, Costanzo, Maria C, Jang, Dongkeun, Burtt, Noël P, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, 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 NA, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M 't, Elders, Petra JM, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth JF, 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 FA, Kiemeney, Lambertus ALM, 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, van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P, Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, 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 KE, Boomsma, Dorret I, Willemsen, Allegonda HM, Cupples, LAdrienne, van Meurs, Joyce BJ, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, 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, YEugene, Ho, Yuk-Lam, Lynch, Julie A, Rader, Daniel J, Tsao, Philip S, Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J, Gaziano, John M, Wilson, Peter WF, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Mohlke, Karen L, Sun, Yan V, Morris, Andrew P, Boehnke, Michael, Brown, Christopher D, Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J, Assimes, Themistocles L, Peloso, Gina M

الوصف: BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

وصف الملف: application/octet-stream; application/zip

العلاقة: https://www.repository.cam.ac.uk/handle/1810/344352Test

الإتاحة: https://doi.org/10.17863/CAM.91776Test
https://www.repository.cam.ac.uk/handle/1810/344352Test

المؤلفون: NCD Risk Factor Collaboration (NCD-RisC), Iurilli, Maria LC, Zhou, Bin, Bennett, James E, Carrillo-Larco, Rodrigo M, Sophiea, Marisa K, Rodriguez-Martinez, Andrea, Bixby, Honor, Solomon, Bethlehem D, Taddei, Cristina, Danaei, Goodarz, Di Cesare, Mariachiara, Stevens, Gretchen A, Riley, Leanne M, Savin, Stefan, Cowan, Melanie J, Bovet, Pascal, Damasceno, Albertino, Chirita-Emandi, Adela, Hayes, Alison J, Ikeda, Nayu, Jackson, Rod T, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Saidi, Olfa, Sebert, Sylvain, Sorić, Maroje, Starc, Gregor, Gregg, Edward W, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmed, Soheir H, Ahrens, Wolfgang, Aitmurzaeva, Gulmira, Ajlouni, Kamel, Al-Hazzaa, Hazzaa M, Al-Lahou, Badreya, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amiri, Parisa, Amougou, Norbert, Amouyel, Philippe, Bo Andersen, Lars, Anderssen, Sigmund A, Ängquist, Lars, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Aung, May Soe, Auvinen, Juha, Avdicová, Mária, Avi, Shina, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Jørgensen, Maja Bæksgaard, Baharudin, Azli, Bahijri, Suhad, Baker, Jennifer L, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Baran, Joanna, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro Virgílio Gomes, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, Batieha, Anwar M, Batista, Rosangela L, Battakova, Zhamilya, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Bel-Serrat, Silvia, Belavendra, Antonisamy, Romdhane, Habiba Ben, Benedics, Judith, Benet, Mikhail, Bergh, Ingunn Holden, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloísa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bhutta, Zulfiqar A, Bi, Hongsheng, Bi, Yufang, Bia, Daniel, Lele, Elysée Claude Bika, Bikbov, Mukharram M, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, Cecilia, Bloch, Katia V, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M, Boehm, Bernhard O, Boeing, Heiner, Boggia, Jose G, Bogova, Elena, Boissonnet, Carlos P, Bojesen, Stig E, Bonaccio, Marialaura, Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthias, Borghs, Herman, Braeckevelt, Lien, Braeckman, Lutgart, Bragt, Marjolijn CE, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Breda, João, Brenner, Hermann, Brewster, Lizzy M, Brian, Garry R, Brinduse, Lacramioara, Brophy, Sinead, Bruno, Graziella, Bueno-de-Mesquita, H Bas, Bugge, Anna, Buoncristiano, Marta, Burazeri, Genc, Burns, Con, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cama, Tilema, Cameron, Christine, Camolas, José, Can, Günay, Cândido, Ana Paula C, Cañete, Felicia, Capanzana, Mario V, Capková, Nadežda, Capuano, Eduardo, Capuano, Vincenzo, Cardol, Marloes, Cardoso, Viviane C, Carlsson, Axel C, Carmuega, Esteban, Carvalho, Joana, Casajús, José A, Casanueva, Felipe F, Celikcan, Ertugrul, Censi, Laura, Cervantes-Loaiza, Marvin, Cesar, Juraci A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nish, Rahim, Norsyamlina Che Abdul, Li Chee, Miao, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheraghian, Bahman, Chetrit, Angela, Chikova-Iscener, Ekaterina, Chiolero, Arnaud, Chiou, Shu-Ti, Chirlaque, María-Dolores, Cho, Belong, Christensen, Kaare, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cilia, Michelle, Cinteza, Eliza, Claessens, Frank, Clarke, Janine, Clays, Els, Cohen, Emmanuel, Concin, Hans, Confortin, Susana C, Cooper, Cyrus, Coppinger, Tara C, Corpeleijn, Eva, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L, Crampin, Amelia C, Crujeiras, Ana B, Csilla, Semánová, Cucu, Alexandra M, Cui, Liufu, Cureau, Felipe V, Czenczek-Lewandowska, Ewelina, D'Arrigo, Graziella, d'Orsi, Eleonora, Dacica, Liliana, Re Saavedra, María Ángeles Dal, Dallongeville, Jean, Damsgaard, Camilla T, Dankner, Rachel, Dantoft, Thomas M, Dasgupta, Parasmani, Dastgiri, Saeed, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, David, De Ridder, Karin, de Rooij, Susanne R, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, Jr DeGennaro, Vincent, Dehghan, Abbas, Delisle, Hélène, Delpeuch, Francis, Demarest, Stefaan, Dennison, Elaine, Dereń, Katarzyna, Deschamps, Valérie, Dhimal, Meghnath, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soares, Díaz-Sánchez, María Elena, Diaz, Alejandro, Dika, Zivka, Djalalinia, Shirin, Djordjic, Visnja, Do, Ha TP, Dobson, Annette J, Donati, Maria Benedetta, Donfrancesco, Chiara, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, Doua, Kouamelan, Dragano, Nico, Drygas, Wojciech, Li Duan, Jia, Duante, Charmaine A, Duboz, Priscilla, Duda, Rosemary B, Duleva, Vesselka, Dulskiene, Virginija, Dumith, Samuel C, Dushpanova, Anar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Eftekhar, Ebrahim, Egbagbe, Eruke E, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elliott, Paul, Engle-Stone, Reina, Enguerran, Macia, Erasmus, Rajiv T, Erbel, Raimund, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, la Peña, Jorge Escobedo-de, Eslami, Saeid, Esmaeili, Ali, Evans, Alun, Faeh, David, Fakhretdinova, Albina A, Fall, Caroline H, Faramarzi, Elnaz, Farjam, Mojtaba, Sant'Angelo, Victoria Farrugia, Farzadfar, Farshad, Fattahi, Mohammad Reza, Fawwad, Asher, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrao, Thomas, Ferrari, Marika, Ferrario, Marco M, Ferreccio, Catterina, Ferrer, Eldridge, Ferrieres, Jean, Figueiró, Thamara Hubler, Fijalkowska, Anna, Fink, Günther, Fischer, Krista, Foo, Leng Huat, Forsner, Maria, Fouad, Heba M, Francis, Damian K, do Carmo Franco, Maria, Frikke-Schmidt, Ruth, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujiati, Isti I, Fujita, Yuki, Fumihiko, Matsuda, Furusawa, Takuro, Gaciong, Zbigniew, Gafencu, Mihai, Galbarczyk, Andrzej, Galenkamp, Henrike, Galeone, Daniela, Galfo, Myriam, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, García-Solano, Marta, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gaya, Adroaldo Cesar Araujo, Gaya, Anelise Reis, Gazzinelli, Andrea, Gehring, Ulrike, Geiger, Harald, Geleijnse, Johanna M, Ghanbari, Ali, Ghasemi, Erfan, Gheorghe-Fronea, Oana-Florentina, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Gironella, Glen, Giwercman, Aleksander, Gkiouras, Konstantinos, Godos, Justyna, Gogen, Sibel, Goldberg, Marcel, Goldsmith, Rebecca A, Goltzman, David, Gómez, Santiago F, Gomula, Aleksandra, da Silva, Bruna Goncalves Cordeiro, Gonçalves, Helen, Gonzalez-Chica, David A, Gonzalez-Gross, Marcela, González-Leon, Margot, González-Rivas, Juan P, González-Villalpando, Clicerio, González-Villalpando, María-Elena, Gonzalez, Angel R, Gottrand, Frederic, Graça, Antonio Pedro, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, Grøholt, Else Karin, Grøntved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Gu, Dongfeng, Gualdi-Russo, Emanuela, Guallar-Castillón, Pilar, Gualtieri, Andrea, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc J, Guo, Xiu-Hua, Guo, Yin, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutiérrez-González, Enrique, Gutierrez, Laura, Gutzwiller, Felix, Ha, Seongjun, Hadaegh, Farzad, Hadjigeorgiou, Charalambos A, Haghshenas, Rosa, Hakimi, Hamid, Halkjær, Jytte, Hambleton, Ian R, Hamzeh, Behrooz, Hange, Dominique, Hanif, Abu AM, Hantunen, Sari, Hao, Jie, Kumar, Rachakulla Hari, Hashemi-Shahri, Seyed Mohammad, Hassapidou, Maria, Hata, Jun, Haugsgjerd, Teresa, He, Jiang, He, Yuan, He, Yuna, Heidinger-Felso, Regina, Heinen, Mirjam, Hejgaard, Tatjana, Hendriks, Marleen Elisabeth, dos Santos Henrique, Rafael, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Herrera, Victor M, Herter-Aeberli, Isabelle, Heshmat, Ramin, Hill, Allan G, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Holdsworth, Michelle, Homayounfar, Reza, Homs, Clara, Hopman, Wilma M, Horimoto, Andrea RVR, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, José María, Huhtaniemi, Ilpo Tapani, Huiart, Laetitia, Petrescu, Constanta Huidumac, Huisman, Martijn, Husseini, Abdullatif, Huu, Chinh Nguyen, Huybrechts, Inge, Hwalla, Nahla, Hyska, Jolanda, Iacoviello, Licia, Ibarluzea, Jesús M, Ibrahim, Mohsen M, Wong, Norazizah Ibrahim, Ikram, M Arfan, Iotova, Violeta, Irazola, Vilma E, Ishida, Takafumi, Islam, Muhammad, Islam, Sheikh Mohammed Shariful, Iwasaki, Masanori, Jacobs, Jeremy M, Jaddou, Hashem Y, Jafar, Tazeen, James, Kenneth, Jamil, Kazi M, Jamrozik, Konrad, Janszky, Imre, Janus, Edward, Jarani, Juel, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jelakovic, Ana, Jelakovic, Bojan, Jennings, Garry, Jha, Anjani Kumar, Jiang, Chao Qiang, Jimenez, Ramon O, Jöckel, Karl-Heinz, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J, Jonas, Jost B, Jonnagaddala, Jitendra, Jørgensen, Torben, Joshi, Pradeep, Joukar, Farahnaz, Jovic, Dragana P, Jóźwiak, Jacek J, Juolevi, Anne, Jurak, Gregor, Simina, Iulia Jurca, Juresa, Vesna, Kaaks, Rudolf, Kaducu, Felix O, Kafatos, Anthony, Kajantie, Eero O, Kalmatayeva, Zhanna, Kalter-Leibovici, Ofra, Kameli, Yves, Kampmann, Freja B, Kanala, Kodanda R, Kannan, Srinivasan, Kapantais, Efthymios, Karakosta, Argyro, Kårhus, Line L, Karki, Khem B, Katibeh, Marzieh, Katz, Joanne, Katzmarzyk, Peter T, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli M, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kelleher, Cecily, Kemper, Han CG, Kengne, Andre P, Keramati, Maryam, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khaw, Kay-Tee, Kheiri, Bahareh, Kheradmand, Motahareh, Khosravi, Alireza, Khouw, Ilse MSL, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Dong Wook, Kim, Hyeon Chang, Kim, Jeongseon, Kindblom, Jenny M, Klakk, Heidi, Klimek, Magdalena, Klimont, Jeannette, Klumbiene, Jurate, Knoflach, Michael, Koirala, Bhawesh, Kolle, Elin, Kolsteren, Patrick, König, Jürgen, Korpelainen, Raija, Korrovits, Paul, Korzycka, Magdalena, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kovacs, Viktoria A, Kowlessur, Sudhir, Koziel, Slawomir, Kratenova, Jana, Kratzer, Wolfgang, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steiner, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kujala, Urho M, Kujundzic, Enisa, Kulaga, Zbigniew, Kumar, R Krishna, Kunešová, Marie, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, La, Quang Ngoc, Laamiri, Fatima Zahra, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Lambrinou, Christina-Paulina, Landais, Edwige, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Latt, Tint Swe, Lauria, Laura, Lazo-Porras, Maria, Le Coroller, Gwenaëlle, Le Nguyen Bao, Khanh, Le Port, Agnès, Le, Tuyen D, Lee, Jeannette, Lee, Jeonghee, Lee, Paul H, Lehmann, Nils, Lehtimäki, Terho, Lemogoum, Daniel, Levitt, Naomi S, Li, Yanping, Liivak, Merike, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lin, Yi-Ting, Lind, Lars, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Liu, Lijuan, Lo, Wei-Cheng, Loit, Helle-Mai, Long, Khuong Quynh, Lopes, Luis, Lopes, Oscar, Lopez-Garcia, Esther, Lopez, Tania, Lotufo, Paulo A, Lozano, José Eugenio, Lukrafka, Janice L, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lunet, Nuno, Lunogelo, Charles, Lustigová, Michala, Łuszczki, Edyta, Ma, Guansheng, Ma, Jun, Ma, Xu, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Macieira, Luisa M, Madar, Ahmed A, Maggi, Stefania, Magliano, Dianna J, Magnacca, Sara, Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Mäki, Päivi, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia K, Maniego, Lynell V, Manios, Yannis, Mann, Jim I, Mansour-Ghanaei, Fariborz, Manzato, Enzo, Margozzini, Paula, Markaki, Anastasia, Markey, Oonagh, Ioannidou, Eliza Markidou, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martin-Prevel, Yves, Martin, Rosemarie, Martorell, Reynaldo, Martos, Eva, Maruszczak, Katharina, Marventano, Stefano, Mascarenhas, Luis P, Masoodi, Shariq R, Mathiesen, Ellisiv B, Mathur, Prashant, Matijasevich, Alicia, Matsha, Tandi E, Mavrogianni, Christina, Mazur, Artur, Mbanya, Jean Claude N, McFarlane, Shelly R, McGarvey, Stephen T, McKee, Martin, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisfjord, Jørgen, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Mensink, Gert BM, Menzano, Maria Teresa, Mereke, Alibek, Meshram, Indrapal I, Metspalu, Andres, Meyer, Haakon E, Mi, Jie, Michaelsen, Kim F, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C, Minderico, Cláudia S, Mini, GK, Miquel, Juan Francisco, Mirjalili, Mohammad Reza, Mirkopoulou, Daphne, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Mistretta, Antonio, Mocanu, Veronica, Modesti, Pietro A, Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K, Mohamed, Shukri F, Mohammad, Kazem, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Molbo, Drude, Møllehave, Line T, Møller, Niels C, Molnár, Dénes, Momenan, Amirabbas, Mondo, Charles K, Monroy-Valle, Michele, Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Morin, Suzanne N, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota-Pinto, Anabela, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Moura-dos-Santos, Marcos André, Mridha, Malay K, Msyamboza, Kelias P, Mu, Thet Thet, Muc, Magdalena, Mugoša, Boban, Muiesan, Maria L, Mukhtorova, Parvina, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M, Najafi, Farid, Nakamura, Harunobu, Námešná, Jana, Ei K Nang, Ei, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Nauck, Matthias, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Liis, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Claes, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pagkalos, Ioannis, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrios, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Pasquet, Patrick, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Pei, Gao, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Marco A, Pérez-Farinós, Napoleón, Pérez, Cynthia M, Peterkova, Valentina, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Petrauskiene, Ausra, Pettenuzzo, Emanuela, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pierannunzio, Daniela, Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N, Plans-Rubió, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Posch, Georg, Poudyal, Anil, Poulimeneas, Dimitrios, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margus, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricardas, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Luis, Rezaianzadeh, Abbas, Ribas-Barba, Lourdes, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santos, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savvas, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Luis, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santos, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinus, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charles, Szklo, Moyses, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Maties, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistoklis, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Tomas, Veidebaum, Toomas, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thomas, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nicholas, Weber, Adelheid, Wedderkopp, Niels, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassilis, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah

مصطلحات موضوعية: Research Article, Epidemiology and Global Health, underweight, obesity, BMI, None

الوصف: Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Test ; Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Test ; From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.

وصف الملف: application/pdf; text/xml; application/zip

العلاقة: https://www.repository.cam.ac.uk/handle/1810/318597Test

الإتاحة: https://doi.org/10.17863/CAM.65712Test
https://www.repository.cam.ac.uk/handle/1810/318597Test

المؤلفون: Nardone, Agostina, Weir, Hazel, Delpuech, Oona, Brown, Henry, De Angelis, Carmine, Cataldo, Maria Letizia, Fu, Xiaoyong, Shea, Martin J, Mitchell, Tamika, Veeraraghavan, Jamunarani, Nagi, Chandandeep, Pilling, Mark, Rimawi, Mothaffar F, Trivedi, Meghana, Hilsenbeck, Susan G, Chamness, Gary C, Jeselsohn, Rinath, Osborne, C Kent, Schiff, Rachel

مصطلحات موضوعية: Animals, Breast Neoplasms, Cell Proliferation, Cinnamates, Drug Resistance, Neoplasm, Estradiol, Estrogens, Female, Fulvestrant, Heterografts, Humans, Indoles, MCF-7 Cells, Mice, Neoplasms, Hormone-Dependent, Receptors, Estrogen, Tamoxifen

الوصف: BACKGROUND: The oestrogen receptor (ER) is an important therapeutic target in ER-positive (ER+) breast cancer. The selective ER degrader (SERD), fulvestrant, is effective in patients with metastatic breast cancer, but its intramuscular route of administration and low bioavailability are major clinical limitations. METHODS: Here, we studied the pharmacology of a new oral SERD, AZD9496, in a panel of in vitro and in vivo endocrine-sensitive and -resistant breast cancer models. RESULTS: In endocrine-sensitive models, AZD9496 inhibited cell growth and blocked ER activity in the presence or absence of oestrogen. In vivo, in the presence of oestrogen, short-term AZD9496 treatment, like fulvestrant, resulted in tumour growth inhibition and reduced expression of ER-dependent genes. AZD9496 inhibited cell growth in oestrogen deprivation-resistant and tamoxifen-resistant cell lines and xenograft models that retain ER expression. AZD9496 effectively reduced ER levels and ER-induced transcription. Expression analysis of short-term treated tumours showed that AZD9496 potently inhibited classic oestrogen-induced gene transcription, while simultaneously increasing expression of genes negatively regulated by ER, including genes potentially involved in escape pathways of endocrine resistance. CONCLUSIONS: These data suggest that AZD9496 is a potent anti-oestrogen that antagonises and degrades ER with anti-tumour activity in both endocrine-sensitive and endocrine-resistant models.

وصف الملف: Print-Electronic; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/300281Test

الإتاحة: https://doi.org/10.17863/CAM.47355Test
https://www.repository.cam.ac.uk/handle/1810/300281Test

المؤلفون: Eijsbouts, Chris, Zheng, Tenghao, Kennedy, Nicholas A., Bonfiglio, Ferdinando, Anderson, Carl A., Moutsianas, Loukas, Holliday, Joanne, Shi, Jingchunzi, Shringarpure, Suyash, Voda, Alexandru-Ioan, Farrugia, Gianrico, Franke, Andre, Hübenthal, Matthias, Abecasis, Gonçalo, Zawistowski, Matthew, Skogholt, Anne Heidi, Ness-Jensen, Eivind, Hveem, Kristian, Esko, Tõnu, Teder-Laving, Maris, Zhernakova, Alexandra, Camilleri, Michael, Boeckxstaens, Guy, Whorwell, Peter J., Spiller, Robin, McVean, Gil, D’Amato, Mauro, Jostins, Luke, Parkes, Miles, Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Clark, Sarah K., Elson, Sarah L., Fletez-Brant, Kipper, Fontanillas, Pierre, Furlotte, Nicholas A., Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., Luff, Marie K., McCreight, Jey C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., Northover, Carrie A. M., O’Connell, Jared, Petrakovitz, Aaron A., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shastri, Anjali J., Shelton, Janie F., Tian, Chao, Tung, Joyce Y., Tunney, Robert J., Vacic, Vladimir, Wang, Xin, Zare, Amir S., Kashyap, Purna, Chang, Lin, Mayer, Emeran, Heitkemper, Margaret, Sayuk, Gregory S., Ringel-Kulka, Tamar, Ringel, Yehuda, Chey, William D., Eswaran, Shanti, Merchant, Juanita L., Shulman, Robert J., Bujanda, Luis, Garcia-Etxebarria, Koldo, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T., Karling, Pontus, Ohlsson, Bodil, Walter, Susanna, Faresjö, Åshild O., Simren, Magnus, Halfvarson, Jonas, Portincasa, Piero, Barbara, Giovanni, Usai-Satta, Paolo, Neri, Matteo, Nardone, Gerardo, Cuomo, Rosario, Galeazzi, Francesca, Bellini, Massimo, Latiano, Anna, Houghton, Lesley, Jonkers, Daisy, Kurilshikov, Alexander, Weersma, Rinse K., Netea, Mihai, Tesarz, Jonas, Gauss, Annika, Goebel-Stengel, Miriam, Andresen, Viola, Frieling, Thomas, Pehl, Christian, Schaefert, Rainer, Niesler, Beate, Lieb, Wolfgang, Hanevik, Kurt, Langeland, Nina, Wensaas, Knut-Arne, Litleskare, Sverre, Gabrielsen, Maiken E., Thomas, Laurent, Thijs, Vincent, Lemmens, Robin, Van Oudenhove, Lukas, Wouters, Mira

مصطلحات موضوعية: Article, /631/208/205/2138, /692/699/1503/1502/2071, /692/699/476, /38/43

الوصف: Funder: Kennedy Trust Rheumatology Research Prize Studentship ; Funder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167) ; Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199Test; Grant(s): 715772 ; Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL ; Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Test ; Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS.

وصف الملف: application/pdf; application/zip; text/xml

العلاقة: https://www.repository.cam.ac.uk/handle/1810/330840Test

الإتاحة: https://doi.org/10.17863/CAM.78283Test
https://www.repository.cam.ac.uk/handle/1810/330840Test

المؤلفون: Jeselsohn, Rinath, Cornwell, MacIntosh, Pun, Matthew, Buchwalter, Gilles, Nguyen, Mai, Bango, Clyde, Huang, Ying, Kuang, Yanan, Paweletz, Cloud, Fu, Xiaoyong, Nardone, Agostina, De Angelis, Carmine, Detre, Simone, Dodson, Andrew, Mohammed, Hisham, Carroll, Jason S, Bowden, Michaela, Rao, Prakash, Long, Henry W, Li, Fugen, Dowsett, Mitchell, Schiff, Rachel, Brown, Myles

مصطلحات موضوعية: SOX9, breast cancer, cistrome, endocrine resistance, estrogen receptor, Antineoplastic Agents, Hormonal, Breast, Breast Neoplasms, Cell Proliferation, Chromatin, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, Female, Humans, MCF-7 Cells, Receptors, Estrogen, SOX9 Transcription Factor, Tamoxifen

الوصف: The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

وصف الملف: application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/291901Test

الإتاحة: https://doi.org/10.17863/CAM.39059Test
https://www.repository.cam.ac.uk/handle/1810/291901Test