المؤلفون: Reinhold SW, Uihlein DC, Böger CA, Kloiber S, Frölich K, Bergler T, Banas B, Schweda F, Krämer BK

المصدر: European Journal of Medical Research, Vol 14, Iss 12, p 520 (2009)

مصطلحات موضوعية: blood pressure, renin angiotensin system, nitric oxide, endothelins, long-term renal artery stenosis, RNAse protection assay, Medicine

الوصف: Abstract Objective Numerous reports have shown the influence of renin, nitric oxide (NO) and the endothelin (ET) systems for regulation of blood pressure and renal function. Furthermore, interactions between these peptides have been reported. Aim of our study was to investigate the relative contribution of these compounds in long-term renovascular hypertension/renal ischemia. Methods Hypertension/left-sided renal ischemia was induced using the 2K1C-Goldblatt rat model. Renal renin, ET-1, ET-3 and endothelial NO synthase (eNOS) gene expression was measured by means of RNAse protection assay at different timepoints up to 10 weeks after induction of renal artery stenosis. Results Plasma renin activity and renal renin gene expression in the left kidney were increased in the clipped animals while eNOS expression was unchanged. Furthermore, an increase in ET-1 expression and a decrease of ET-3 expression was detected in early stenosis. Conclusions While renin is obviously involved in regulation of blood pressure and renal function in unilateral renal artery stenosis, ET-1, ET-3 and endothelium derived NO do not appear to play an important role in renal adaptation processes in long-term renal artery stenosis, although ET-1 and ET-3 might be involved in short-term adaptation processes.

وصف الملف: electronic resource

العلاقة: http://www.eurjmedres.com/content/14/12/520Test; https://doaj.org/toc/2047-783XTest

الوصول الحر: https://doaj.org/article/672ce9bd55cc46d48fac3b7196618c01Test

المؤلفون: Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lüll, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rüeger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Cañadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jäger, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jørgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Kårhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikäinen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Møllehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Pärna, K, Pauper, M, Petersen, ERB, Petersen, LV, Pitkänen, N, Polašek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RC, Smit, RAJ, Smith, AV, Smith, JA, Smyth, LJ, Southam, L, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, DSP, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Bin Wei, W, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Åsvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Böger, CA, Bønnelykke, K, Boomsma, DI, Børglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DPV, Janaka de Silva, H, Dedoussis, GV, den Hollander, AI, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmståhl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, BI, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hyppönen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jöckel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kähönen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, AV, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Köttgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimäki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Mägi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, März, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellström, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nöthen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, JI, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, 't Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tönjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusié-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Völker, U, Vollenweider, P, Völzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, DI, Cho, YS, Heid, IM, McCarthy, MI, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, YV, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, SI, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN

الوصف: This is the final version. Available on open access from Nature Research via the DOI in this record ; Data availability: Summary statistics for ancestry-specific and multi-ancestry GWASs (excluding data from 23andMe) as well as SNP weights for polygenic scores derived in this study are made publicly available on the GIANT consortium website (see ‘URLs’ for GIANT consortium data files). GWAS summary statistics derived involving 23andMe participants will be made available to qualified researchers under an agreement with 23andMe that protects the privacy of participants. Application for data access can be submitted at https://research.23andme.com/dataset-accessTest/. We used genotypes from various publicly available databases to estimate linkage disequilibrium correlations required for conditional analyses and genome-wide prediction analyses. These databases include the UK Biobank under project 12505 and the database of Genotypes and Phenotypes (dbGaP) under project 15096. Accession numbers for dbGaP datasets are phs000788.v2.p3.c1, phs000386, phs000557.v4.p1, phs000286.v5.p1, phs000613.v1.p2, phs000284.v2.p1, phs000283.v7.p3 and phs001395.v2.p1 cohorts. Details for each dbGaP dataset are given in the Methods. Source data are provided with this paper. ; Code availability: We used publicly available software tools for all analyses. These software tools are listed in the main text and in the Methods. Source data are provided with this paper. ; Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering ...

وصف الملف: 704-712

العلاقة: https://www.ncbi.nlm.nih.gov/pubmed/36224396Test; orcid:0000-0003-1726-948X (Wood, Andrew R); Vol. 610 (7933), pp. 704-712; https://doi.org/10.1038/s41586-022-05275-yTest; http://hdl.handle.net/10871/131725Test; Nature

الإتاحة: https://doi.org/10.1038/s41586-022-05275-yTest
http://hdl.handle.net/10871/131725Test

المؤلفون: Kanoni, S, Graham, SE, Wang, Y, Surakka, I, Ramdas, S, Zhu, X, Clarke, SL, Bhatti, KF, Vedantam, S, Winkler, TW, Locke, AE, Marouli, E, Zajac, GJM, Wu, K-HH, Ntalla, I, Hui, Q, Klarin, D, Hilliard, AT, Wang, Z, Xue, C, Thorleifsson, G, Helgadottir, A, Gudbjartsson, DF, Holm, H, Olafsson, I, Hwang, MY, Han, S, Akiyama, M, Sakaue, S, Terao, C, Kanai, M, Zhou, W, Brumpton, BM, Rasheed, H, Havulinna, AS, Veturi, Y, Pacheco, JA, Rosenthal, EA, Lingren, T, Feng, Q, Kullo, IJ, Narita, A, Takayama, J, Martin, HC, Hunt, KA, Trivedi, B, Haessler, J, Giulianini, F, Bradford, Y, Miller, JE, Campbell, A, Lin, K, Millwood, IY, Rasheed, A, Hindy, G, Faul, JD, Zhao, W, Weir, DR, Turman, C, Huang, H, Graff, M, Choudhury, A, Sengupta, D, Mahajan, A, Brown, MR, Zhang, W, Yu, K, Schmidt, EM, Pandit, A, Gustafsson, S, Yin, X, Luan, J, Zhao, J-H, Matsuda, F, Jang, H-M, Yoon, K, Medina-Gomez, C, Pitsillides, A, Hottenga, JJ, Wood, AR, Ji, Y, Gao, Z, Haworth, S, Yousri, NA, Mitchell, RE, Chai, JF, Aadahl, M, Bjerregaard, AA, Yao, J, Manichaikul, A, Hwu, C-M, Hung, Y-J, Warren, HR, Ramirez, J, Bork-Jensen, J, Kårhus, LL, Goel, A, Sabater-Lleal, M, Noordam, R, Mauro, P, Matteo, F, McDaid, AF, Marques-Vidal, P, Wielscher, M, Trompet, S, Sattar, N, Møllehave, LT, Munz, M, Zeng, L, Huang, J, Yang, B, Poveda, A, Kurbasic, A, Lamina, C, Forer, L, Scholz, M, Galesloot, TE, Bradfield, JP, Ruotsalainen, SE, Daw, E, Zmuda, JM, Mitchell, JS, Fuchsberger, C, Christensen, H, Brody, JA, Vazquez-Moreno, M, Feitosa, MF, Wojczynski, MK, Preuss, MH, Mangino, M, Christofidou, P, Verweij, N, Benjamins, JW, Engmann, J, Tsao, NL, Verma, A, Slieker, RC, Lo, KS, Zilhao, NR, Le, P, Kleber, ME, Delgado, GE, Huo, S, Ikeda, DD, Iha, H, Yang, J, Liu, J, Demirkan, A, Leonard, HL, Marten, J, Frank, M, Schmidt, B, Smyth, LJ, Cañadas-Garre, M, Wang, C, Nakatochi, M, Wong, A, Hutri-Kähönen, N, Sim, X, Xia, R, Huerta-Chagoya, A, Fernandez-Lopez, JC, Lyssenko, V, Nongmaithem, SS, Bayyana, S, Stringham, HM, Irvin, MR, Oldmeadow, C, Kim, H-N, Ryu, S, Timmers, PRHJ, Arbeeva, L, Dorajoo, R, Lange, LA, Prasad, G, Lorés-Motta, L, Pauper, M, Long, J, Li, X, Theusch, E, Takeuchi, F, Spracklen, CN, Loukola, A, Bollepalli, S, Warner, SC, Wang, YX, Wei, WB, Nutile, T, Ruggiero, D, Sung, YJ, Chen, S, Liu, F, Kentistou, KA, Banas, B, Nardone, GG, Meidtner, K, Bielak, LF, Smith, JA, Hebbar, P, Farmaki, A-E, Hofer, E, Lin, M, Concas, MP, Vaccargiu, S, van der Most, PJ, Pitkänen, N, Cade, BE, van der Laan, SW, Chitrala, KN, Weiss, S, Bentley, AR, Doumatey, AP, Adeyemo, AA, Lee, JY, Petersen, ERB, Nielsen, AA, Choi, HS, Nethander, M, Freitag-Wolf, S, Southam, L, Rayner, NW, Wang, CA, Lin, S-Y, Wang, J-S, Couture, C, Lyytikäinen, L-P, Nikus, K, Cuellar-Partida, G, Vestergaard, H, Hidalgo, B, Giannakopoulou, O, Cai, Q, Obura, MO, van Setten, J, Liang, J, Tang, H, Terzikhan, N, Shin, JH, Jackson, RD, Reiner, AP, Martin, LW, Chen, Z, Li, L, Kawaguchi, T, Thiery, J, Bis, JC, Launer, LJ, Li, H, Nalls, MA, Raitakari, OT, Ichihara, S, Wild, SH, Nelson, CP, Campbell, H, Jäger, S, Nabika, T, Al-Mulla, F, Niinikoski, H, Braund, PS, Kolcic, I, Kovacs, P, Giardoglou, T, Katsuya, T, de Kleijn, D, de Borst, GJ, Kim, EK, Adams, HHH, Ikram, MA, Asselbergs, FW, Kraaijeveld, AO, Beulens, JWJ, Shu, X-O, Rallidis, LS, Pedersen, O, Hansen, T, Mitchell, P, Hewitt, AW, Kähönen, M, Pérusse, L, Bouchard, C, Tönjes, A, Chen, Y-DI, Pennell, CE, Mori, TA, Lieb, W, Franke, A, Ohlsson, C, Mellström, D, Cho, YS, Lee, H, Yuan, J-M, Koh, W-P, Rhee, SY, Woo, J-T, Heid, IM, Stark, KJ, Zimmermann, ME, Völzke, H, Homuth, G, Evans, MK, Zonderman, AB, Polasek, O, Pasterkamp, G, Hoefer, IE, Redline, S, Pahkala, K, Oldehinkel, AJ, Snieder, H, Biino, G, Schmidt, R, Schmidt, H, Bandinelli, S, Dedoussis, G, Thanaraj, TA, Kardia, SLR, Peyser, PA, Kato, N, Schulze, MB, Girotto, G, Böger, CA, Jung, B, Joshi, PK, Bennett, DA, De Jager, PL, Lu, X, Mamakou, V, Brown, M, Caulfield, MJ, Munroe, PB, Guo, X, Ciullo, M, Jonas, JB, Samani, NJ, Kaprio, J, Pajukanta, P, Tusié-Luna, T, Aguilar-Salinas, CA, Adair, LS, Bechayda, SA, de Silva, HJ, Wickremasinghe, AR, Krauss, RM, Wu, J-Y, Zheng, W, Hollander, AI, Bharadwaj, D, Correa, A, Wilson, JG, Lind, L, Heng, C-K, Nelson, AE, Golightly, YM, Wilson, JF, Penninx, B, Kim, H-L, Attia, J, Scott, RJ, Rao, DC, Arnett, DK, Hunt, SC, Walker, M, Koistinen, HA, Chandak, GR, Mercader, JM, Costanzo, MC, Jang, D, Burtt, NP, Villalpando, CG, Orozco, L, Fornage, M, Tai, E, van Dam, RM, Lehtimäki, T, Chaturvedi, N, Yokota, M, Reilly, DF, McKnight, AJ, Kee, F, Jöckel, K-H, McCarthy, MI, Palmer, CNA, Vitart, V, Hayward, C, Simonsick, E, van Duijn, CM, Jin, Z-B, Qu, J, Hishigaki, H, Lin, X, März, W, Gudnason, V, Tardif, J-C, Lettre, G, Hart, LMT, Elders, PJM, Damrauer, SM, Kumari, M, Kivimaki, M, van der Harst, P, Spector, TD, Loos, RJF, Province, MA, Parra, EJ, Cruz, M, Psaty, BM, Brandslund, I, Pramstaller, PP, Rotimi, CN, Christensen, K, Ripatti, S, Widén, E, Hakonarson, H, Grant, SFA, Kiemeney, LALM, de Graaf, J, Loeffler, M, Kronenberg, F, Gu, D, Erdmann, J, Schunkert, H, Franks, PW, Linneberg, A, Jukema, JW, Khera, AV, Männikkö, M, Jarvelin, M-R, Kutalik, Z, Francesco, C, Mook-Kanamori, DO, van Dijk, KW, Watkins, H, Strachan, DP, Grarup, N, Sever, P, Poulter, N, Chuang, L-M, Rotter, JI, Dantoft, TM, Karpe, F, Neville, MJ, Timpson, NJ, Cheng, C-Y, Wong, T-Y, Khor, CC, Sabanayagam, C, Peters, A, Gieger, C, Hattersley, AT, Pedersen, NL, Magnusson, PKE, Boomsma, DI, Willemsen, AHM, Cupples, L, van Meurs, JBJ, Ghanbari, M, Gordon-Larsen, P, Huang, W, Kim, YJ, Tabara, Y, Wareham, NJ, Langenberg, C, Zeggini, E, Kuusisto, J, Laakso, M, Ingelsson, E, Abecasis, G, Chambers, JC, Kooner, JS, de Vries, PS, Morrison, AC, Hazelhurst, S, Ramsay, M, North, KE, Daviglus, M, Kraft, P, Martin, NG, Whitfield, JB, Abbas, S, Saleheen, D, Walters, RG, Holmes, MV, Black, C, Smith, BH, Baras, A, Justice, AE, Buring, JE, Ridker, PM, Chasman, DI, Kooperberg, C, Tamiya, G, Yamamoto, M, van Heel, DA, Trembath, RC, Wei, W-Q, Jarvik, GP, Namjou, B, Hayes, MG, Ritchie, MD, Jousilahti, P, Salomaa, V, Hveem, K, Åsvold, BO, Kubo, M, Kamatani, Y, Okada, Y, Murakami, Y, Kim, B-J, Thorsteinsdottir, U, Stefansson, K, Zhang, J, Chen, Y, Ho, Y-L, Lynch, JA, Rader, DJ, Tsao, PS, Chang, K-M, Cho, K, O'Donnell, CJ, Gaziano, JM, Wilson, PWF, Frayling, TM, Hirschhorn, JN, Kathiresan, S, Mohlke, KL, Sun, YV, Morris, AP, Boehnke, M, Brown, CD, Natarajan, P, Deloukas, P, Willer, CJ, Assimes, TL, Peloso, GM

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; application/vnd.ms-excel; application/vnd.openxmlformats-officedocument.wordprocessingml.document

العلاقة: https://openaccess.sgul.ac.uk/id/eprint/115047/1/GLGC_Kanoni_LipidsBiology_Manuscript_Accepted_2022Dec04.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/6/s13059-022-02837-1.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/11/13059_2022_2837_MOESM1_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/12/13059_2022_2837_MOESM2_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/13/13059_2022_2837_MOESM3_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/18/13059_2022_2837_MOESM4_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/19/13059_2022_2837_MOESM5_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/20/13059_2022_2837_MOESM6_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/25/13059_2022_2837_MOESM7_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/26/13059_2022_2837_MOESM8_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/27/13059_2022_2837_MOESM9_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/32/13059_2022_2837_MOESM10_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/33/13059_2022_2837_MOESM11_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/38/13059_2022_2837_MOESM12_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/39/13059_2022_2837_MOESM13_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/44/13059_2022_2837_MOESM14_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/49/13059_2022_2837_MOESM15_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/54/13059_2022_2837_MOESM16_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/59/13059_2022_2837_MOESM17_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/60/13059_2022_2837_MOESM18_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/61/13059_2022_2837_MOESM19_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/62/13059_2022_2837_MOESM20_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/63/13059_2022_2837_MOESM21_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/64/13059_2022_2837_MOESM22_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/65/13059_2022_2837_MOESM23_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/66/13059_2022_2837_MOESM24_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/71/13059_2022_2837_MOESM25_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/72/13059_2022_2837_MOESM26_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/77/13059_2022_2837_MOESM27_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/78/13059_2022_2837_MOESM28_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/79/13059_2022_2837_MOESM29_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/80/13059_2022_2837_MOESM30_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/81/13059_2022_2837_MOESM31_ESM.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115047/89/13059_2022_2837_MOESM32_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/90/13059_2022_2837_MOESM33_ESM.xlsxTest; https://openaccess.sgul.ac.uk/id/eprint/115047/91/13059_2022_2837_MOESM34_ESM.docxTest; Kanoni, S; Graham, SE; Wang, Y; Surakka, I; Ramdas, S; Zhu, X; Clarke, SL; Bhatti, KF; Vedantam, S; Winkler, TW; et al. 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Genome Biol, 23 (1). p. 268. ISSN 1474-760X https://doi.org/10.1186/s13059-022-02837-1Test SGUL Authors: Strachan, David Peter

الإتاحة: https://doi.org/10.1186/s13059-022-02837-1Test
https://openaccess.sgul.ac.uk/id/eprint/115047Test/
https://openaccess.sgul.ac.uk/id/eprint/115047/1/GLGC_Kanoni_LipidsBiology_Manuscript_Accepted_2022Dec04.pdfTest
https://openaccess.sgul.ac.uk/id/eprint/115047/6/s13059-022-02837-1.pdfTest
https://openaccess.sgul.ac.uk/id/eprint/115047/11/13059_2022_2837_MOESM1_ESM.xlsxTest
https://openaccess.sgul.ac.uk/id/eprint/115047/12/13059_2022_2837_MOESM2_ESM.xlsxTest
https://openaccess.sgul.ac.uk/id/eprint/115047/13/13059_2022_2837_MOESM3_ESM.pdfTest
https://openaccess.sgul.ac.uk/id/eprint/115047/18/13059_2022_2837_MOESM4_ESM.xlsxTest
https://openaccess.sgul.ac.uk/id/eprint/115047/19/13059_2022_2837_MOESM5_ESM.xlsxTest
https://openaccess.sgul.ac.uk/id/eprint/115047/20/13059_2022_2837_MOESM6_ESM.pdfTest

المؤلفون: Winkler, TW, Rasheed, H, Teumer, A, Gorski, M, Rowan, BX, Stanzick, KJ, Thomas, LF, Tin, A, Hoppmann, A, Chu, AY, Tayo, B, Thio, CHL, Cusi, D, Chai, J-F, Sieber, KB, Horn, K, Li, M, Scholz, M, Cocca, M, Wuttke, M, Van der Most, PJ, Yang, Q, Ghasemi, S, Nutile, T, Li, Y, Pontali, G, Guenther, F, Dehghan, A, Correa, A, Parsa, A, Feresin, A, De Vries, APJ, Zonderman, AB, Smith, A, Oldehinkel, AJ, De Grandi, A, Rosenkranz, AR, Franke, A, Teren, A, Metspalu, A, Hicks, AA, Morris, AP, Toenjes, A, Morgan, A, Podgornaia, A, Peters, A, Koerner, A, Mahajan, A, Campbell, A, Freedman, B, Spedicati, B, Ponte, B, Schoettker, B, Brumpton, B, Banas, B, Kraemer, BK, Jung, B, Asvold, BO, Smith, BH, Ning, B, Penninx, BWJH, Vanderwerff, BR, Psaty, BM, Kammerer, CM, Langefeld, CD, Hayward, C, Spracklen, CN, Robinson-Cohen, C, Hartman, CA, Lindgren, CM, Wang, C, Sabanayagam, C, Heng, C-K, Lanzani, C, Khor, C-C, Cheng, C-Y, Fuchsberger, C, Gieger, C, Shaffer, CM, Schulz, C-A, Willer, CJ, Chasman, D, Gudbjartsson, DF, Ruggiero, D, Toniolo, D, Czamara, D, Porteous, DJ, Waterworth, DM, Mascalzoni, D, Mook-Kanamori, DO, Reilly, DF, Daw, EW, Hofer, E, Boerwinkle, E, Salvi, E, Bottinger, EP, Tai, E-S, Catamo, E, Rizzi, F, Guo, F, Rivadeneira, F, Guilianini, F, Sveinbjornsson, G, Ehret, G, Waeber, G, Biino, G, Girotto, G, Pistis, G, Nadkarni, GN, Delgado, GE, Montgomery, GW, Snieder, H, Campbell, H, White, HD, Gao, H, Stringham, HM, Schmidt, H, Li, H, Brenner, H, Holm, H, Kirsten, H, Kramer, H, Rudan, I, Nolte, IM, Tzoulaki, I, Olafsson, I, Martins, J, Cook, JP, Wilson, JF, Halbritter, J, Felix, JF, Divers, J, Kooner, JS, Lee, JJ-M, O'Connell, J, Rotter, J, Liu, J, Xu, J, Thiery, J, Arnlov, J, Kuusisto, J, Jakobsdottir, J, Tremblay, J, Chambers, JC, Whitfield, JB, Gaziano, JM, Marten, J, Coresh, J, Jonas, JB, Mychaleckyj, JC, Christensen, K, Eckardt, K-U, Mohlke, KL, Endlich, K, Dittrich, K, Ryan, KA, Rice, KM, Taylor, KD, Ho, K, Nikus, K, Matsuda, K, Strauch, K, Miliku, K, Hveem, K, Lind, L, Wallentin, L, Yerges-Armstrong, LM, Raffield, LM, Phillips, LS, Launer, LJ, Lyytikainen, L-P, Lange, LA, Citterio, L, Klaric, L, Ikram, MA, Ising, M, Kleber, ME, Francescatto, M, Concas, MP, Ciullo, M, Piratsu, M, Orho-Melander, M, Laakso, M, Loeffler, M, Perola, M, De Borst, MH, Gogele, M, La Bianca, M, Lukas, MA, Feitosa, MF, Biggs, ML, Wojczynski, MK, Kavousi, M, Kanai, M, Akiyama, M, Yasuda, M, Nauck, M, Waldenberger, M, Chee, M-L, Boehnke, M, Preuss, MH, Stumvoll, M, Province, MA, Evans, MK, O'Donoghue, ML, Kubo, M, Kahonen, M, Kastarinen, M, Nalls, MA, Kuokkanen, M, Ghanbari, M, Bochud, M, Josyula, NS, Martin, NG, Tan, NYQ, Palmer, ND, Pirastu, N, Schupf, N, Verweij, N, Hutri-Kahonen, N, Mononen, N, Bansal, N, Devuyst, O, Melander, O, Raitakari, OT, Polasek, O, Manunta, P, Gasparini, P, Mishra, PP, Sulem, P, Magnusson, PKE, Elliott, P, Ridker, PM, Hamet, P, Svensson, PO, Joshi, PK, Kovacs, P, Pramstaller, PP, Rossing, P, Vollenweider, P, Van der Harst, P, Dorajoo, R, Sim, RZH, Burkhardt, R, Tao, R, Noordam, R, Magi, R, Schmidt, R, De Mutsert, R, Rueedi, R, Van Dam, RM, Carroll, RJ, Gansevoort, RT, Loos, RJF, Felicita, SC, Sedaghat, S, Padmanabhan, S, Freitag-Wolf, S, Pendergrass, SA, Graham, SE, Gordon, SD, Hwang, S-J, Kerr, SM, Vaccargiu, S, Patil, SB, Hallan, S, Bakker, SJL, Lim, S-C, Lucae, S, Vogelezang, S, Bergmann, S, Corre, T, Ahluwalia, TS, Lehtimaki, T, Boutin, TS, Meitinger, T, Wong, T-Y, Bergler, T, Rabelink, TJ, Esko, T, Haller, T, Thorsteinsdottir, U, Voelker, U, Foo, VHX, Salomaa, V, Vitart, V, Giedraitis, V, Gudnason, V, Jaddoe, VWV, Huang, W, Zhang, W, Wei, WB, Kiess, W, Marz, W, Koenig, W, Lieb, W, Gao, X, Sim, X, Wang, YX, Friedlander, Y, Tham, Y-C, Kamatani, Y, Okada, Y, Milaneschi, Y, Yu, Z, Stark, KJ, Stefansson, K, Boeger, CA, Hung, AM, Kronenberg, F, Koettgen, A, Pattaro, C, Heid, IM

المساهمون: Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), UK DRI Ltd

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Biology, Multidisciplinary Sciences, Life Sciences & Biomedicine - Other Topics, Science & Technology - Other Topics, GENOME-WIDE ASSOCIATION, ENVIRONMENT INTERACTION, QUALITY-CONTROL, METAANALYSIS, LOCI, JOINT, EFFICIENT, SMOKING, DISEASE, EXPRESSION, Lifelines cohort study, DiscovEHR/MyCode study, VA Million Veteran Program, Kidney, Humans, Diabetic Nephropathies, Diabetes Mellitus, Creatinine, Glomerular Filtration Rate, Genome-Wide Association Study

الوصف: 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 (nDM = 178,691, nnoDM = 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.

العلاقة: Communications Biology; http://hdl.handle.net/10044/1/97937Test; 7370192; RDF03; MR/S019669/1; MR/R023484/1; MR/L01632X/1; DRI-CORE2020-IMP

الإتاحة: https://doi.org/10.1038/s42003-022-03448-zTest
http://hdl.handle.net/10044/1/97937Test

المؤلفون: Sawitzki, B, Harden, PN, Reinke, P, Moreau, A, Hutchinson, JA, Game, DS, Tang, Q, Guinan, EC, Battaglia, M, Burlingham, WJ, Roberts, ISD, Streitz, M, Josien, R, Böger, CA, Scottà, C, Markmann, JF, Hester, JL, Juerchott, K, Braudeau, C, James, B, Contreras-Ruiz, L, van der Net, JB, Bergler, T, Caldara, R, Petchey, W, Edinger, M, Dupas, N, Kapinsky, M, Mutzbauer, I, Otto, NM, Öllinger, R, Hernandez-Fuentes, MP, Issa, F, Ahrens, N, Meyenberg, C, Karitzky, S, Kunzendorf, U, Knechtle, SJ, Grinyó, J, Morris, PJ, Brent, L, Bushell, A, Turka, LA, Bluestone, JA, Lechler, RI, Schlitt, HJ, Cuturi, MC, Schlickeiser, S, Friend, PJ, Miloud, T, Scheffold, A, Secchi, A, Crisalli, K, Kang, SM, Hilton, R, Banas, B, Blancho, G, Volk, HD, Lombardi, G, Wood, KJ, Geissler, EK

الوصف: Data sharing: We will follow the common controlled access principles outlined by the Medical Research Council Clinical Trials Unit. According to those principles, we will acknowledge that data with long-term value be preserved, and usable for future research. We do, however, want to ensure that there are legal, ethical, and commercial constraints maintained on the release of research data according to the following code. Research teams are entitled to receive appropriate recognition for their efforts in collecting and analysing data and should be given at least a limited period of sole access to use and publish the data, before key trial data are open for use by other researchers. If such requests are made to access the data, resources need to be available to process the request and prepare the data in a timely manner, if possible. Because of these demands, there must be an important scientific objective behind each request. Especially in the case of our international project, The ONE Study, any request must comply with regulations set by the competent authorities in the relevant countries that govern data security policies. ; Supplementary material is available online at: https://www.sciencedirect.com/science/article/pii/S0140673620301677#sec1Test . ; Background: Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. Methods: The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell ...

وصف الملف: 1627 - 1639; Print-Electronic

العلاقة: The Lancet; ORCiD: Cristiano Scottà orcid:0000-0003-3942-5201; Sawitzki, B. et al. (2020) 'Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials', The Lancet, 395 (10237), pp. 1627 - 1639. doi:10.1016/S0140-6736(20)30167-7.; https://bura.brunel.ac.uk/handle/2438/29198Test; https://doi.org/10.1016/S0140-6736Test(20)30167-7

الإتاحة: https://doi.org/10.1016/S0140-6736Test(20)30167-7
https://bura.brunel.ac.uk/handle/2438/29198Test

المؤلفون: Graham, SE, Clarke, SL, Wu, K-HH, Kanoni, S, Zajac, GJM, Ramdas, S, Surakka, I, Ntalla, I, Vedantam, S, Winkler, TW, Locke, AE, Mollehave, LT, Thuesen, BH, Munz, M, Zeng, L, Huang, J, Yang, B, Poveda, A, Kurbasic, A, Lamina, C, Forer, L, Marouli, E, Scholz, M, Galesloot, TE, Bradfield, JP, Daw, EW, Zmuda, JM, Mitchell, JS, Fuchsberger, C, Christensen, H, Brody, JA, Feitosa, MF, Hwang, MY, Wojczynski, MK, Preuss, M, Mangino, M, Christofidou, P, Verweij, N, Benjamins, JW, Engmann, J, Kember, RL, Slieker, RC, Lo, KS, Han, S, Zilhao, NR, Le, P, Kleber, ME, Delgado, GE, Huo, S, Ikeda, DD, Iha, H, Yang, J, Liu, J, Leonard, HL, Narita, A, Marten, J, Schmidt, B, Arendt, M, Smyth, LJ, Canadas-Garre, M, Wang, C, Nakatochi, M, Wong, A, Hutri-Kahonen, N, Sim, X, Choudhury, A, Xia, R, Huerta-Chagoya, A, Fernandez-Lopez, JC, Lyssenko, V, Ahmed, M, Jackson, AU, Yousri, NA, Irvin, MR, Oldmeadow, C, Kim, H-N, Bentley, AR, Ryu, S, Timmers, PRHJ, Arbeeva, L, Dorajoo, R, Lange, LA, Chai, X, Prasad, G, Lores-Motta, L, Pauper, M, Long, J, Ekoru, K, Li, X, Theusch, E, Takeuchi, F, Spracklen, CN, Loukola, A, Bollepalli, S, Warner, SC, Wang, YX, Wei, WB, Nutile, T, Verma, A, Ruggiero, D, Sung, YJ, Hung, Y-J, Chen, S, Liu, F, Kentistou, KA, Gorski, M, Brumat, M, Meidtner, K, Trivedi, B, Bielak, LF, Smith, JA, Hebbar, P, Farmaki, A-E, Hofer, E, Lin, M, Xue, C, Zhang, J, Concas, MP, Vaccargiu, S, Martin, HC, Van der Most, PJ, Pitkanen, N, Cade, BE, Lee, J, Van der Laan, SW, Chitrala, KN, Weiss, S, Zimmermann, ME, Lee, JY, Choi, HS, Hunt, KA, Nethander, M, Freitag-Wolf, S, Southam, L, Rayner, NW, Wang, CA, Lin, S-Y, Wang, J-S, Couture, C, Lyytikainen, L-P, Nikus, K, Hui, Q, Cuellar-Partida, G, Vestergaard, H, Hildalgo, B, Giannakopoulou, O, Cai, Q, Obura, MO, Van Setten, J, Schwander, K, Terzikhan, N, Klarin, D, Shin, JH, Jackson, RD, Reiner, AP, Martin, LW, Chen, Z, Li, L, Highland, HM, Young, KL, Kawaguchi, T, Thiery, J, Zhu, X, Bis, JC, Nadkarni, GN, Launer, LJ, Li, H, Nalls, MA, Raitakari, OT, Ichihara, S, Wild, SH, Nelson, CP, Campbell, H, Thorleifsson, G, Jaeger, S, Nabika, T, Al-Mulla, F, Niinikoski, H, Braund, PS, Kolcic, I, Kovacs, P, Giardoglou, T, Katsuya, T, Bhatti, KF, Helgadottir, A, De Kleijn, D, De Borst, GJ, Kim, EK, Adams, HHH, Ikram, MA, Asselbergs, FW, Kraaijeveld, AO, Beulens, JWJ, Shu, X-O, Gudbjartsson, DF, Rallidis, LS, Pedersen, O, Hansen, T, Mitchell, P, Hewitt, AW, Kahonen, M, Perusse, L, Bouchard, C, Toenjes, A, Chen, Y-DI, Holm, H, Pennell, CE, Mori, TA, Lieb, W, Franke, A, Ohlsson, C, Mellstrom, D, Cho, YS, Lee, H, Yuan, J-M, Koh, W-P, Olafsson, I, Rhee, SY, Woo, J-T, Heid, IM, Stark, KJ, Voelzke, H, Homuth, G, Evans, MK, Zonderman, AB, Polasek, O, Pasterkamp, G, Akiyama, M, Hoefer, IE, Redline, S, Pahkala, K, Oldehinkel, AJ, Snieder, H, Biino, G, Schmidt, R, Schmidt, H, Chen, YE, Bandinelli, S, Sakaue, S, Dedoussis, G, Thanaraj, TA, Kardia, SLR, Kato, N, Schulze, MB, Girotto, G, Jung, B, Boeger, CA, Joshi, PK, Bennett, DA, Terao, C, De Jager, PL, Lu, X, Mamakou, V, Brown, M, Caulfield, MJ, Munroe, PB, Guo, X, Ciullo, M, Jonas, JB, Samani, NJ, Kanai, M, Kaprio, J, Pajukanta, P, Adair, LS, Bechayda, SA, De Silva, HJ, Wickremasinghe, AR, Krauss, RM, Wu, J-Y, Zheng, W, Den Hollander, AI, Zhou, W, Bharadwaj, D, Correa, A, Wilson, JG, Lind, L, Heng, C-K, Nelson, AE, Golightly, YM, Wilson, JF, Penninx, B, Kim, H-L, Brumpton, BM, Attia, J, Scott, RJ, Rao, DC, Arnett, DK, Hunt, SC, Walker, M, Koistinen, HA, Chandak, GR, Yajnik, CS, Mercader, JM, Rasheed, H, Tusie-Luna, T, Aguilar-Salinas, CA, Villalpando, CG, Orozco, L, Fornage, M, Tai, ES, Van Dam, RM, Lehtimaki, T, Chaturvedi, N, Yokota, M, Ruotsalainen, SE, Reilly, DF, McKnight, AJ, Kee, F, Joeckel, K-H, McCarthy, MI, Palmer, CNA, Vitart, V, Hayward, C, Simonsick, E, Havulinna, AS, Van Duijn, CM, Lu, F, Qu, J, Hishigaki, H, Lin, X, Maerz, W, Parra, EJ, Cruz, M, Gudnason, V, Tardif, J-C, Veturi, Y, Lettre, G, 't Hart, LM, Elders, PJM, Damrauer, SM, Kumari, M, Kivimaki, M, Van der Harst, P, Spector, TD, Loos, RJF, Province, MA, Feng, Q, Psaty, BM, Brandslund, I, Pramstaller, PP, Christensen, K, Ripatti, S, Widen, E, Hakonarson, H, Grant, SFA, Kiemeney, LALM, De Graaf, J, Rosenthal, EA, Loeffler, M, Kronenberg, F, Gu, D, Erdmann, J, Schunkert, H, Franks, PW, Linneberg, A, Jukema, JW, Khera, AV, Mannikko, M, Lingren, T, Jarvelin, M-R, Kutalik, Z, Cucca, F, Mook-Kanamori, DO, Van Dijk, KW, Watkins, H, Strachan, DP, Grarup, N, Sever, P, Poulter, N, Pacheco, JA, Rotter, JI, Dantoft, TM, Karpe, F, Neville, MJ, Timpson, NJ, Cheng, C-Y, Wong, T-Y, Khor, CC, Sabanayagam, C, Peters, A, Pendergrass, SA, Gieger, C, Hattersley, AT, Pedersen, NL, Magnusson, PKE, Boomsma, DI, De Geus, EJC, Cupples, LA, Van Meurs, JBJ, Ghanbari, M, Gordon-Larsen, P, Haessler, J, Huang, W, Kim, YJ, Tabara, Y, Wareham, NJ, Langenberg, C, Zeggini, E, Kuusisto, J, Laakso, M, Ingelsson, E, Abecasis, G, Giulianini, F, Chambers, JC, Kooner, JS, De Vries, PS, Morrison, AC, North, KE, Daviglus, M, Kraft, P, Martin, NG, Whitfield, JB, Abbas, S, Bradford, Y, Saleheen, D, Walters, RG, Holmes, MV, Black, C, Smith, BH, Justice, AE, Baras, A, Buring, JE, Ridker, PM, Chasman, DI, Miller, JE, Kooperberg, C, Wei, W-Q, Jarvik, GP, Namjou, B, Hayes, MG, Ritchie, MD, Jousilahti, P, Salomaa, V, Hveem, K, Asvold, BO, Campbell, A, Kubo, M, Kamatani, Y, Okada, Y, Murakami, Y, Thorsteinsdottir, U, Stefansson, K, Ho, Y-L, Lynch, JA, Rader, DJ, Tsao, PS, Lin, K, Chang, K-M, Cho, K, O'Donnell, CJ, Gaziano, JM, Wilson, P, Rotimi, CN, Hazelhurst, S, Ramsay, M, Trembath, RC, Van Heel, DA, Millwood, IY, Tamiya, G, Yamamoto, M, Kim, B-J, Mohlke, KL, Frayling, TM, Hirschhorn, JN, Kathiresan, S, Boehnke, M, Natarajan, P, Peloso, GM, Hindy, G, Brown, CD, Morris, AP, Assimes, TL, Deloukas, P, Sun, YV, Willer, CJ, Rasheed, A, Faul, JD, Zhao, W, Weir, DR, Turman, C, Huang, H, Graff, M, Mahajan, A, Brown, MR, Zhang, W, Yu, K, Schmidt, EM, Pandit, A, Gustafsson, S, Yin, X, Luan, J, Zhao, J-H, Matsuda, F, Jang, H-M, Yoon, K, Medina-Gomez, C, Pitsillides, A, Hottenga, JJ, Willemsen, G, Wood, AR, Ji, Y, Gao, Z, Haworth, S, Mitchell, RE, Chai, JF, Aadahl, M, Yao, J, Manichaikul, A, Warren, HR, Ramirez, J, Bork-Jensen, J, Karhus, LL, Goel, A, Sabater-Lleal, M, Noordam, R, Sidore, C, Fiorillo, E, McDaid, AF, Marques-Vidal, P, Wielscher, M, Trompet, S, Sattar, N

المصدر: E20 ; E19

العلاقة: Nature; http://hdl.handle.net/10044/1/107123Test

الإتاحة: https://doi.org/10.1038/s41586-023-06194-2Test
http://hdl.handle.net/10044/1/107123Test

المؤلفون: Teumer A, Li Y, Ghasemi S, Prins BP, Wuttke M, Hermle T, Giri A, Sieber KB, Qiu C, Kirsten H, Tin A, Chu AY, Bansal N, Feitosa MF, Wang L, Chai JF, Cocca M, Fuchsberger C, Gorski M, Hoppmann A, Horn K, Li M, Marten J, Noce D, Nutile T, Sedaghat S, Sveinbjornsson G, Tayo BO, van der Most PJ, Xu Y, Yu Z, Gerstner L, Ärnlöv J, Bakker SJL, Baptista D, Biggs ML, Boerwinkle E, Brenner H, Burkhardt R, Carroll RJ, Chee ML, Chen M, Cheng CY, Cook JP, Coresh J, Corre T, Danesh J, de Borst MH, De Grandi A, de Mutsert R, de Vries APJ, Degenhardt F, Dittrich K, Divers J, Eckardt KU, Ehret G, Endlich K, Felix JF, Franco OH, Franke A, Freedman BI, Freitag-Wolf S, Gansevoort RT, Giedraitis V, Gögele M, Grundner-Culemann F, Gudbjartsson DF, Gudnason V, Hamet P, Harris TB, Hicks AA, Holm H, Foo VHX, Hwang SJ, Ikram MA, Ingelsson E, Jaddoe VWV, Jakobsdottir J, Josyula NS, Jung B, Kähönen M, Khor CC, Kiess W, Koenig W, Körner A, Kovacs P, Kramer H, Krämer BK, Kronenberg F, Lange LA, Langefeld CD, Lee JJ, Lehtimäki T, Lieb W, Lim SC, Lind L, Lindgren CM, Liu J, Loeffler M, Lyytikäinen LP, Mahajan A, Maranville JC, Mascalzoni D, McMullen B, Meisinger C, Meitinger T, Miliku K, Mook-Kanamori DO, Müller-Nurasyid M, Mychaleckyj JC, Nauck M, Nikus K, Ning B, Noordam R, Connell JO, Olafsson I, Palmer ND, Peters A, Podgornaia AI, Ponte B, Poulain T, Pramstaller PP, Rabelink TJ, Raffield LM, Reilly DF, Rettig R, Rheinberger M, Rice KM, Rivadeneira F, Runz H, Ryan KA, Sabanayagam C, Saum KU, Schöttker B, Shaffer CM, Shi Y, Smith AV, Strauch K, Stumvoll M, Sun BB, Szymczak S, Tai ES, Tan NYQ, Taylor KD, Teren A, Tham YC, Thiery J, Thio CHL, Thomsen H, Thorsteinsdottir U, Tönjes A, Tremblay J, Uitterlinden AG, van der Harst P, Verweij N, Vogelezang S, Völker U, Waldenberger M, Wang C, Wilson OD, Wong C, Wong TY, Yang Q, Yasuda M, Akilesh S, Bochud M, Böger CA, Devuyst O, Edwards TL, Ho K, Morris AP, Parsa A, Pendergrass SA, Psaty BM, Rotter JI, Stefansson K, Wilson JG, Susztak K, Snieder H, Heid IM, Scholz M, Butterworth AS, Hung AM, Pattaro C, Köttgen A

الوصف: 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. ; open

وصف الملف: application/pdf

العلاقة: http://dx.doi.org/10.1038/s41467-019-11576-0Test; https://www.nature.com/articles/s41467-019-11576-0Test; https://bia.unibz.it/handle/10863/12164Test

الإتاحة: https://doi.org/10.1038/s41467-019-11576-0Test
https://www.nature.com/articles/s41467-019-11576-0Test
https://bia.unibz.it/handle/10863/12164Test

المؤلفون: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Blueher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boeger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Toenjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Voelker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF

المصدر: Nature Genetics , 50 pp. 26-41. (2018)

الوصف: 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.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10069029/3/Turcot_Maroli%20Protein-altering%20variants%20associated%20with%20BMI%20Accepted%202017.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10069029Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10069029/3/Turcot_Maroli%20Protein-altering%20variants%20associated%20with%20BMI%20Accepted%202017.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10069029Test/

المؤلفون: Gorski, Mathias, van der Most, Peter J., Li, Yong, Sedaghat, S, Smith, AV, Sorice, R, Stengel, B, Stracke, S, Strauch, K, Toniolo, D, Uitterlinden, AG, Ulivi, S, Viikari, JS, Tayo, Bamidele, Voelker, U, Vollenweider, P, Voelzke, H, Vuckovic, D, Waldenberger, M, Wang, JJ, Yang, Q, Chasman, DI, Tromp, G, Snieder, H, Tin, Adrienne, Heid, IM, Fox, CS, Koettgen, A, Pattaro, C, Boeger, CA, Fuchsberger, C, Feitosa, Mary F., Aspelund, Thor, Attia, John, Biffar, Reiner, Bochud, Murielle, Boerwinkle, Eric, Borecki, Ingrid, Teumer, Alexander, Bottinger, Erwin P., Chen, Ming-Huei, Chouraki, Vincent, Ciullo, Marina, Coresh, Josef, Cornelis, Marilyn C., Curhan, Gary C., d'Adamo, Adamo P., Dehghan, Abbas, Dengler, Laura, Chu, Audrey Y., Ding, Jingzhong, Eiriksdottir, Gudny, Endlich, K, Enroth, S, Esko, T, Franco, OH, Gasparini, P, Gieger, C, Girotto, G, Gottesman, O, Li, Man, Gudnason, V, Gyllensten, U, Hancock, Stephen J., Harris, TB, Helmer, C, Hoellerer, S, Hofer, E, Hofman, A, Holliday, Elizabeth, Homuth, G, Mijatovic, Vladan, Hu, FB, Huth, C, Hutri-Kahonen, N, Hwang, S-J, Imboden, M, Johansson, A, Kahonen, M, Koenig, W, Kraemer, H, Kramer, BK, Nolte, Ilja M., Kumar, A, Kutalik, Z, Lambert, J-C, Launer, LJ, Lehtimaki, T, de Borst, M, Navis, G, Swertz, M, Liu, Y, Lohman, K, Cocca, Massimiliano, Loos, RJF, Lu, Y, Lyytikainen, L-P, McEvoy, Mark A., Meisinger, C, Meitinger, T, Metspalu, A, Metzger, M, Mihailov, E, Mitchell, P, Taliun, Daniel, Nauck, M, Oldehinkel, AJ, Olden, M, Penninx, BWJH, Pistis, G, Pramstaller, PP, Probst-Hensch, N, Raitakari, OT, Rettig, R, Ridker, PM, Gomez, Felicia, Rivadeneira, F, Robino, A, Rosas, SE, Ruderfer, D, Ruggiero, D, Saba, Y., Sala, C., Schmidt, H, Schmidt, R, Scott, Rodney J.

المساهمون: The University of Newcastle. Faculty of Health & Medicine, School of Medicine and Public Health

مصطلحات موضوعية: chronic kidney disease, genome-wide association studies, The 1000 Genomes project, kidney function

الوصف: 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.

العلاقة: Scientific Reports Vol. 7, no. 45040; http://hdl.handle.net/1959.13/1352081Test; uon:30822

الإتاحة: http://hdl.handle.net/1959.13/1352081Test

المؤلفون: Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, VA, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renström, F, Wu, J, Qi, Q, Ahmad, S, Alfred, T, Amin, N, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Neergaard Harder, M, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikäinen, L-P, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Müller-Nurasyid, M, Navarro, P, Pérusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stančáková, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, Van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N, Vink, JM, Vitart, V, Wu, Y, Yengo, L, Zhang, W, Hua Zhao, J, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Jan Hottenga, J, Huang, J, Hung, J, Hutri-Kähönen, N, Ingelsson, E, James, AL, Jansson, J-O, Jarvelin, M-R, Jhun, MA, Jørgensen, ME, Juonala, M, Kähönen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Krämer, BK, Kuusisto, J, Kvaløy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Männikkö, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellström, D, Menni, C, Montgomery, GW, Musk, AB, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, S, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE, Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, AG, Vandenput, L, Vohl, M-C, Völzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, MC, Baldassarre, D, Balkau, B, Bandinelli, S, Böger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, Y-D, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, Faire, UD, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, H-J, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Wouter Jukema, J, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimäki, T, Marchand, LL, März, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sørensen, TIA, Strauch, K, Tiemeier, H, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, van Duijn, CM, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpeläinen, TO, Liu, C-T, Borecki, IB, North, KE, Cupples, LA

مصطلحات موضوعية: Adiposity, Adult, Body Fat Distribution, Body Mass Index, Epistasis, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Smoking, Waist Circumference, Waist-Hip Ratio

الوصف: 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. ; See Acknowledgements section

وصف الملف: application/pdf; application/vnd.openxmlformats-officedocument.presentationml.presentation; image/tiff

العلاقة: https://www.repository.cam.ac.uk/handle/1810/265012Test

الإتاحة: https://doi.org/10.17863/CAM.10749Test
https://www.repository.cam.ac.uk/handle/1810/265012Test