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6. Climate clubs : politically feasible and desirable?

Author

Falkner, R., Nasiritousi, Naghmeh, Reischl, G., Falkner, R., Nasiritousi, Naghmeh, and Reischl, G.

Abstract

The idea of a stringent climate club, once the reserve of academic debates, is quickly gaining ground in international policy circles. This reflects dissatisfaction with the multilateral UNFCCC process, but also hope that a minilateral club could increase climate policy ambition, reinvigorate the Paris Agreement process, and make future emissions pledges stick. With the Biden Presidency renewing the US commitment toward climate action and the European Green Deal proposal for carbon border tariffs, some are advocating the creation of a transatlantic climate club. What could a club approach hope to achieve, and what do we know about its political feasibility and desirability? In this article, we seek conceptual clarification by establishing a typology of different club models; we inject a greater sense of political realism into current debates on the feasibility of these models; and we consider their legitimacy in the context of international climate cooperation. Key policy insights Knowledge gaps and confusion regarding the nature of climate clubs hold back debates about what intergovernmental clubs can contribute to international climate policy. Club design matters: existing club models vary in terms of the proposed size, purpose, operational principles, legal strength, and relationship to the UNFCCC. Clubs focused on normative commitments face low barriers to establishment. They lack legal strength but can help raise policy ambition. Clubs aimed at negotiating targets and measures can increase bargaining efficiency, but struggle to deal with equity and distributional conflicts. Clubs seeking to change incentives via club benefits and sanctions face the highest hurdles to implementation. Their promise to tackle free-riding remains untested and difficult to achieve. Climate clubs face an international legitimacy deficit. Any club proposal needs to consider how to add to, and not distract from, the multilateral climate regime.

Published
2022
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7. Status-Quo-Erhebung zur Zyklotron-Infrastruktur für die Nuklearmedizin und Radiopharmazie in Deutschland, Österreich und der Schweiz (D-A-CH)

Author

Zippel, C., Ermert, J., Patt, M., Gildehaus, F. J., Ross, T., Reischl, G., Kuwert, T., Solbach, C., Neumaier, B., (0000-0001-7431-0026) Kiß, O., Mitterhauser, M., Wadsak, W., Schibli, R., (0000-0003-4846-1271) Kopka, K., Zippel, C., Ermert, J., Patt, M., Gildehaus, F. J., Ross, T., Reischl, G., Kuwert, T., Solbach, C., Neumaier, B., (0000-0001-7431-0026) Kiß, O., Mitterhauser, M., Wadsak, W., Schibli, R., and (0000-0003-4846-1271) Kopka, K.

Abstract

Zyklotrone bilden als Ressource medizinischer Radionuklide eine zentrale Infrastruktur für die Entwicklung neuer und die Produktion klinisch etablierter Radiotracer zur molekularen Hybridbildgebung. Da die letzte umfassende Veröffentlichung zu Zyklotronen ca. 15 Jahre alt ist, wurde eine Statuserhebung zu den für die Nuklearmedizin und Radiopharmazie in Deutschland, Österreich und der Schweiz (D-A-CH-Länder) betriebenen Zyklotronen angestrebt.

Published
2022

8. Cyclotrons operated for Nuclear Medicine and Radiopharmacy in the German speaking D-A-CH countries: An update on current status and trends

Author

Zippel, C., Ermert, J., Patt, M., Gildehaus, F. J., Ross, T. L., Reischl, G., Neumaier, B., (0000-0001-7431-0026) Kiß, O., Mitterhauser, M., Wadsak, W., Schibli, R., (0000-0003-4846-1271) Kopka, K., Zippel, C., Ermert, J., Patt, M., Gildehaus, F. J., Ross, T. L., Reischl, G., Neumaier, B., (0000-0001-7431-0026) Kiß, O., Mitterhauser, M., Wadsak, W., Schibli, R., and (0000-0003-4846-1271) Kopka, K.

Abstract

Background: Cyclotrons form a central infrastructure and are a resource of medical radionu- clides for the development of new radiotracers as well as the production and supply of clini- cally established radiopharmaceuticals for patient care in nuclear medicine. Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharma- ceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) vali- dated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results: In total, 39 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 29 of them in Germany, 4 in Austria and 6 in Switzerland. The majority of the cyclotrons reported (69%) are operated by universities, university hospitals or research institutions close to a university (clinic), less by/in cooperation with industrial partners (26%) or a (non-university) clinic/PET-center (5%). Most of the cyclotrons (82%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion: The data presented provide an academically-updated overview of the medical cy- clotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medi- cine in the D-A-CH countries. In this context, we discuss current developments and trends with a

Published
2022

32. Translational immunoPET/MR imaging of invasive pulmonary aspergillosis

Author

Schwenck, J, additional, Beziere, N, additional, Maurer, A, additional, Wild, AM, additional, Henneberg, H, additional, Davies, G, additional, Reischl, G, additional, Spycher, PR, additional, Wehrmüller, JE, additional, Boschetti, F, additional, Wiehr, S, additional, Schibli, R, additional, Gunzer, M, additional, Thornton, C, additional, and Pichler, BJ, additional

Published
2019
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35. Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium

Author

Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), London, S.J. (Stephanie J.), Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), and London, S.J. (Stephanie J.)

Published
2018
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41. OR2-1Low μu-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis

Author

Hermann, D, primary, Hirth, N, additional, Reimold, M, additional, Batra, A, additional, Smolka, M N, additional, Hoffmann, S, additional, Kiefer, F, additional, Noori, H R, additional, Sommer, W H, additional, Reischl, G, additional, La Fougère, C, additional, Mann, K, additional, Spanagel, R, additional, and Hansson, A C, additional

Published
2017
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48. Hypoxia-specific tumor imaging with F-18-fluoroazomycin arabinoside

Author

Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, Wester HJ, Beck R, McEwan AJB, Wiebe LI, Schwaiger M., Piert, M, Machulla, Hj, Picchio, M, Reischl, G, Ziegler, S, Kumar, P, Wester, Hj, Beck, R, Mcewan, Ajb, Wiebe, Li, and Schwaiger, M.

Abstract

The study was performed to compare the F-18-labeled nitroimidazole compound fluoroazomycin arabinoside (F-18-FAZA) with the standard hypoxia tracer fluoromisonidazole (F-18-FMISO) in detection of tumor tissue hypoxia and to verify the oxygenation dependency of F-18-FAZA uptake. Methods: Biodistribution of F-18-FAZA was studied at various time points in EMT6 tumor-bearing BALB/c mice and in AR42J and A431 tumor-bearing nude mice and compared with that of F-18-FMISO. The presence of tumor tissue hypoxia was verified in 5 EMT6 and 5 AR42J tumors using an oxygen-sensing needle electrode system. To evaluate the oxygenation dependency of F-18-FAZA uptake, using the Munich prototype animal PET scanner, 2 serial PET scans were performed in 13 A431 tumor-bearing nude mice breathing pure oxygen or room air on 1 d and then selecting the other oxygen breathing condition on the following day. In addition, digital autoradiography was performed with EMT6 tumor-bearing F-18-FAZA-dosed, nude mice breathing either room air (n = 8) or carbogen (n = 9). Results: Tissue partial pressure of oxygen (Po-2) electrode measurements revealed that tumor hypoxia was present under room air breathing in EMT6 (tissue Po-2 = 2.9 +/- 2.6) and AR42J tumors (tissue Po-2 = 0.4 +/- 0.2), which was significantly lower compared with that of reference tissue (tissue Po-2 = 25.8 +/- 6.7 and tissue Po-2 29.0 +/- 3.0 [mean +/- SD], respectively; P < 0.01). In all tumor models, F-18-FAZA displayed significantly higher tumor-to-muscle and tumor-to-blood ratios compared with F-18-FMISO, indicating a faster clearance of F-18-FAZA from normal tissues. In AR42J tumors, F-18-FAZA tumor-to-normal ratios were found to increase overtime. Serial animal F-18-FAZA PET studies showed that the tumor-to-background ratio was significantly higher in animals breathing room air compared with that of animals breathing pure oxygen (7.3 +/- 2.3 vs. 4.2 +/- 1.2, respectively; P < 0.001). Similarly, autoradiography showed significantly higher tumor-to-muscle ratios in mice breathing room air compared with those of animals breathing carbogen (5.3 +/- 0.8 vs. 2.2 +/- 0.8; respectively; P < 0.02). Conclusion: F-18-FAZA shows superior biokinetics and is, thus, a promising PET tracer for the visualization of tumor hypoxia. This study also verified a hypoxia-specific uptake mechanism for F-18-FAZA in murine tumor models.

Published
2005

49. Modulation of genetic associations with serum urate levels by body-mass-index in humans

Author

Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), Vitart, V. (Veronique), Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), and Vitart, V. (Veronique)

Abstract

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 × 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 × 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight = 9.1 × 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (P difflean-obese= 2 × 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obsogenic environment.

Published
2015
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