3 results on '"Zeng LY"'
Search Results
2. A genomic exploration identifies mechanisms that may explain adverse cardiovascular effects of COX-2 inhibitors
- Author
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Braenne, I, Willenborg, C, Tragante, V, Kessler, T, Zeng, LY, Reiz, B, Kleinecke, M, von Ameln, S, Willer, CJ, Laakso, M, Wild, PS, Zeller, T, Wallentin, L, Franks, PW, Salomaa, V, Dehghan, Abbas, Meitinger, T, Samani, NJ, Asselbergs, FW, Erdmann, J, Schunkert, H, Braenne, I, Willenborg, C, Tragante, V, Kessler, T, Zeng, LY, Reiz, B, Kleinecke, M, von Ameln, S, Willer, CJ, Laakso, M, Wild, PS, Zeller, T, Wallentin, L, Franks, PW, Salomaa, V, Dehghan, Abbas, Meitinger, T, Samani, NJ, Asselbergs, FW, Erdmann, J, and Schunkert, H
- Published
- 2017
3. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- Author
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Freitag, DF, Butterworth, AS, Willeit, P, Howson, JMM, Burgess, S, Kaptoge, S, Young, R, Ho, WK, Wood, AM, Sweeting, M, Spackman, S, Staley, JR, Ramond, A, Harshfield, E, Nielsen, SF, Grande, P, Lange, LA, Bown, MJ, Jones, GT, Scott, RA, Bevan, S, Porcu, E, Thorleifsson, G, Zeng, LY, Kessler, T, Nikpay, M, Do, R, Zhang, WH, Hopewell, JC, Kleber, M, Delgado, GE, Nelson, CP, Goel, A, Bis, JC, Dehghan, Abbas, Ligthart, Symen, Smith, AV, Qu, LM, van 't Hof, FNG, de Bakker, PIW, Baas, AF, van Rij, A, Tromp, G, Kuivaniemi, H, Ritchie, MD, Verma, SS, Crawford, DC, Malinowski, J, de Andrade, M, Kullo, IJ, Peissig, PL, McCarty, CA, Bottinger, EP, Gottesman, O, Crosslin, DR, Carrell, DS, Rasmussen-Torvik, LJ, Pacheco, JA, Huang, J, Timpson, NJ, Kettunen, J, Ala-Korpela, M, Mitchell, GF, Parsa, A, Wilkinson, IB, Gorski, M, Li, Yunlei, Franceschini, N, Keller, MF, Ganesh, SK, Langefeld, CD, Bruijn, L, Brown, MA, Evans, DM, Baltic, S, Ferreira, MA, Baurecht, H, Weidinger, S, Franke, A, Lubitz, SA, Muller-Nurasyid, M, Felix, Janine, Smith, NL, Sudman, M, Thompson, SD, Zeggini, E, Panoutsopoulou, K, Nalls, MA, Singleton, A, Polychronakos, C, Bradfield, JP, Hakonarson, H, Easton, DF, Thompson, D, Tomlinson, IP, Dunlop, M, Hemminki, K, Morgan, G, Eisen, T, Goldschmidt, H, Allan, JM, Henrion, M, Whiffin, N, Wang, YF, Chubb, D, Houlston, RS, Iles, MM, Bishop, DT, Law, MH, Hayward, NK, Luo, Y, Nejentsev, S, Barbalic, M, Crossman, D, Sanna, S, Soranzo, N, Markus, HS, Wareham, NJ, Rader, DJ, O Reilly, M, Assimes, T, Harris, TB, Hofman, Bert, Franco Duran, OH, Gudnason, V, Tracy, R, Psaty, BM, Farrall, M, Watkins, H, Hall, AS, Samani, NJ, Marz, W, Clarke, R, Collins, R, Kooner, JS, Chambers, JC, Kathiresan, S, McPherson, R, Erdmann, J, Kastrati, A, Schunkert, H, Stefansson, K, Thorsteinsdottir, U, Walston, JD, Tybjaerg-Hansen, A, Alam, DS, Majumder, AA, Di Angelantonio, E, Chowdhury, R, Nordestgaard, BG, Saleheen, D, Thompson, SG, Danesh, J, Freitag, DF, Butterworth, AS, Willeit, P, Howson, JMM, Burgess, S, Kaptoge, S, Young, R, Ho, WK, Wood, AM, Sweeting, M, Spackman, S, Staley, JR, Ramond, A, Harshfield, E, Nielsen, SF, Grande, P, Lange, LA, Bown, MJ, Jones, GT, Scott, RA, Bevan, S, Porcu, E, Thorleifsson, G, Zeng, LY, Kessler, T, Nikpay, M, Do, R, Zhang, WH, Hopewell, JC, Kleber, M, Delgado, GE, Nelson, CP, Goel, A, Bis, JC, Dehghan, Abbas, Ligthart, Symen, Smith, AV, Qu, LM, van 't Hof, FNG, de Bakker, PIW, Baas, AF, van Rij, A, Tromp, G, Kuivaniemi, H, Ritchie, MD, Verma, SS, Crawford, DC, Malinowski, J, de Andrade, M, Kullo, IJ, Peissig, PL, McCarty, CA, Bottinger, EP, Gottesman, O, Crosslin, DR, Carrell, DS, Rasmussen-Torvik, LJ, Pacheco, JA, Huang, J, Timpson, NJ, Kettunen, J, Ala-Korpela, M, Mitchell, GF, Parsa, A, Wilkinson, IB, Gorski, M, Li, Yunlei, Franceschini, N, Keller, MF, Ganesh, SK, Langefeld, CD, Bruijn, L, Brown, MA, Evans, DM, Baltic, S, Ferreira, MA, Baurecht, H, Weidinger, S, Franke, A, Lubitz, SA, Muller-Nurasyid, M, Felix, Janine, Smith, NL, Sudman, M, Thompson, SD, Zeggini, E, Panoutsopoulou, K, Nalls, MA, Singleton, A, Polychronakos, C, Bradfield, JP, Hakonarson, H, Easton, DF, Thompson, D, Tomlinson, IP, Dunlop, M, Hemminki, K, Morgan, G, Eisen, T, Goldschmidt, H, Allan, JM, Henrion, M, Whiffin, N, Wang, YF, Chubb, D, Houlston, RS, Iles, MM, Bishop, DT, Law, MH, Hayward, NK, Luo, Y, Nejentsev, S, Barbalic, M, Crossman, D, Sanna, S, Soranzo, N, Markus, HS, Wareham, NJ, Rader, DJ, O Reilly, M, Assimes, T, Harris, TB, Hofman, Bert, Franco Duran, OH, Gudnason, V, Tracy, R, Psaty, BM, Farrall, M, Watkins, H, Hall, AS, Samani, NJ, Marz, W, Clarke, R, Collins, R, Kooner, JS, Chambers, JC, Kathiresan, S, McPherson, R, Erdmann, J, Kastrati, A, Schunkert, H, Stefansson, K, Thorsteinsdottir, U, Walston, JD, Tybjaerg-Hansen, A, Alam, DS, Majumder, AA, Di Angelantonio, E, Chowdhury, R, Nordestgaard, BG, Saleheen, D, Thompson, SG, and Danesh, J
- Abstract
Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who ca
- Published
- 2015
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