TY - JOUR A1 - Warrington, Nicole A1 - Beaumont, Robin A1 - Horikoshi, Momoko A1 - Day, Felix R. A1 - Helgeland, Øyvind A1 - Laurin, Charles A1 - Bacelis, Jonas A1 - Peng, Shouneng A1 - Hao, Ke A1 - Feenstra, Bjarke A1 - Wood, Andrew R. A1 - Mahajan, Anubha A1 - Tyrrell, Jessica A1 - Robertson, Neil R. A1 - Rayner, N. William A1 - Qiao, Zhen A1 - Moen, Gunn-Helen A1 - Vaudel, Marc A1 - Marsit, Carmen A1 - Chen, Jia A1 - Nodzenski, Michael A1 - Schnurr, Theresia M. A1 - Zafarmand, Mohammad Hadi A1 - Bradfield, Jonathan P. A1 - Grarup, Niels A1 - Kooijman, Marjolein N. A1 - Li-Gao, Ruifang A1 - Geller, Frank A1 - Ahluwalia, Tarunveer Singh A1 - Paternoster, Lavinia A1 - Rueedi, Rico A1 - Huikari, Ville A1 - Hottenga, Jouke-Jan A1 - Lyytikäinen, Leo-Pekka A1 - Cavadino, Alana A1 - Metrustry, Sarah A1 - Cousminer, Diana L. A1 - Wu, Ying A1 - Thiering, Elisabeth Paula A1 - Wang, Carol A. A1 - Have, Christian Theil A1 - Vilor-Tejedor, Natalia A1 - Joshi, Peter K. A1 - Painter, Jodie N. A1 - Ntalla, Ioanna A1 - Myhre, Ronny A1 - Pitkänen, Niina A1 - van Leeuwen, Elisabeth M. A1 - Joro, Raimo A1 - Lagou, Vasiliki A1 - Richmond, Rebecca C. A1 - Espinosa, Ana A1 - Barton, Sheila J. A1 - Inskip, Hazel M. A1 - Holloway, John W. A1 - Santa-Marina, Loreto A1 - Estivill, Xavier A1 - Ang, Wei A1 - Marsh, Julie A. A1 - Reichetzeder, Christoph A1 - Marullo, Letizia A1 - Hocher, Berthold A1 - Lunetta, Kathryn L. A1 - Murabito, Joanne M. A1 - Relton, Caroline L. A1 - Kogevinas, Manolis A1 - Chatzi, Leda A1 - Allard, Catherine A1 - Bouchard, Luigi A1 - Hivert, Marie-France A1 - Zhang, Ge A1 - Muglia, Louis J. A1 - Heikkinen, Jani A1 - Morgen, Camilla S. A1 - van Kampen, Antoine H. C. A1 - van Schaik, Barbera D. C. A1 - Mentch, Frank D. A1 - Langenberg, Claudia A1 - Scott, Robert A. A1 - Zhao, Jing Hua A1 - Hemani, Gibran A1 - Ring, Susan M. A1 - Bennett, Amanda J. A1 - Gaulton, Kyle J. A1 - Fernandez-Tajes, Juan A1 - van Zuydam, Natalie R. A1 - Medina-Gomez, Carolina A1 - de Haan, Hugoline G. A1 - Rosendaal, Frits R. A1 - Kutalik, Zoltán A1 - Marques-Vidal, Pedro A1 - Das, Shikta A1 - Willemsen, Gonneke A1 - Mbarek, Hamdi A1 - Müller-Nurasyid, Martina A1 - Standl, Marie A1 - Appel, Emil V. R. A1 - Fonvig, Cilius Esmann A1 - Trier, Caecilie A1 - van Beijsterveldt, Catharina E. M. A1 - Murcia, Mario A1 - Bustamante, Mariona A1 - Bonàs-Guarch, Sílvia A1 - Hougaard, David M. A1 - Mercader, Josep M. A1 - Linneberg, Allan A1 - Schraut, Katharina E. A1 - Lind, Penelope A. A1 - Medland, Sarah Elizabeth A1 - Shields, Beverley M. A1 - Knight, Bridget A. A1 - Chai, Jin-Fang A1 - Panoutsopoulou, Kalliope A1 - Bartels, Meike A1 - Sánchez, Friman A1 - Stokholm, Jakob A1 - Torrents, David A1 - Vinding, Rebecca K. A1 - Willems, Sara M. A1 - Atalay, Mustafa A1 - Chawes, Bo L. A1 - Kovacs, Peter A1 - Prokopenko, Inga A1 - Tuke, Marcus A. A1 - Yaghootkar, Hanieh A1 - Ruth, Katherine S. A1 - Jones, Samuel E. A1 - Loh, Po-Ru A1 - Murray, Anna A1 - Weedon, Michael N. A1 - Tönjes, Anke A1 - Stumvoll, Michael A1 - Michaelsen, Kim Fleischer A1 - Eloranta, Aino-Maija A1 - Lakka, Timo A. A1 - van Duijn, Cornelia M. A1 - Kiess, Wieland A1 - Koerner, Antje A1 - Niinikoski, Harri A1 - Pahkala, Katja A1 - Raitakari, Olli T. A1 - Jacobsson, Bo A1 - Zeggini, Eleftheria A1 - Dedoussis, George V. A1 - Teo, Yik-Ying A1 - Saw, Seang-Mei A1 - Montgomery, Grant W. A1 - Campbell, Harry A1 - Wilson, James F. A1 - Vrijkotte, Tanja G. M. A1 - Vrijheid, Martine A1 - de Geus, Eco J. C. N. A1 - Hayes, M. Geoffrey A1 - Kadarmideen, Haja N. A1 - Holm, Jens-Christian A1 - Beilin, Lawrence J. A1 - Pennell, Craig E. A1 - Heinrich, Joachim A1 - Adair, Linda S. A1 - Borja, Judith B. A1 - Mohlke, Karen L. A1 - Eriksson, Johan G. A1 - Widen, Elisabeth E. A1 - Hattersley, Andrew T. A1 - Spector, Tim D. A1 - Kaehoenen, Mika A1 - Viikari, Jorma S. A1 - Lehtimaeki, Terho A1 - Boomsma, Dorret I. A1 - Sebert, Sylvain A1 - Vollenweider, Peter A1 - Sorensen, Thorkild I. A. A1 - Bisgaard, Hans A1 - Bonnelykke, Klaus A1 - Murray, Jeffrey C. A1 - Melbye, Mads A1 - Nohr, Ellen A. A1 - Mook-Kanamori, Dennis O. A1 - Rivadeneira, Fernando A1 - Hofman, Albert A1 - Felix, Janine F. A1 - Jaddoe, Vincent W. V. A1 - Hansen, Torben A1 - Pisinger, Charlotta A1 - Vaag, Allan A. A1 - Pedersen, Oluf A1 - Uitterlinden, Andre G. A1 - Jarvelin, Marjo-Riitta A1 - Power, Christine A1 - Hypponen, Elina A1 - Scholtens, Denise M. A1 - Lowe, William L. A1 - Smith, George Davey A1 - Timpson, Nicholas J. A1 - Morris, Andrew P. A1 - Wareham, Nicholas J. A1 - Hakonarson, Hakon A1 - Grant, Struan F. A. A1 - Frayling, Timothy M. A1 - Lawlor, Debbie A. A1 - Njolstad, Pal R. A1 - Johansson, Stefan A1 - Ong, Ken K. A1 - McCarthy, Mark I. A1 - Perry, John R. B. A1 - Evans, David M. A1 - Freathy, Rachel M. T1 - Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors JF - Nature genetics N2 - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming. Y1 - 2019 SN - 1061-4036 SN - 1546-1718 VL - 51 IS - 5 SP - 804 EP - + PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Zheng, Ju-Sheng A1 - Luan, Jian'an A1 - Sofianopoulou, Eleni A1 - Imamura, Fumiaki A1 - Stewart, Isobel D. A1 - Day, Felix R. A1 - Pietzner, Maik A1 - Wheeler, Eleanor A1 - Lotta, Luca A. A1 - Gundersen, Thomas E. A1 - Amiano, Pilar A1 - Ardanaz, Eva A1 - Chirlaque, Maria-Dolores A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Kaaks, Rudolf A1 - Laouali, Nasser A1 - Mancini, Francesca Romana A1 - Nilsson, Peter M. A1 - Onland-Moret, N. Charlotte A1 - Olsen, Anja A1 - Overvad, Kim A1 - Panico, Salvatore A1 - Palli, Domenico A1 - Ricceri, Fulvio A1 - Rolandsson, Olov A1 - Spijkerman, Annemieke M. W. A1 - Sanchez, Maria-Jose A1 - Schulze, Matthias Bernd A1 - Sala, Nuria A1 - Sieri, Sabina A1 - Tjonneland, Anne A1 - Tumino, Rosario A1 - van der Schouw, Yvonne T. A1 - Weiderpass, Elisabete A1 - Riboli, Elio A1 - Danesh, John A1 - Butterworth, Adam S. A1 - Sharp, Stephen J. A1 - Langenberg, Claudia A1 - Forouhi, Nita G. A1 - Wareham, Nicholas J. T1 - Plasma vitamin C and type 2 diabetes BT - genome-wide association study and Mendelian randomization analysis in European populations JF - Diabetes care N2 - OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention. Y1 - 2020 U6 - https://doi.org/10.2337/dc20-1328 SN - 0149-5992 SN - 1935-5548 VL - 44 IS - 1 SP - 98 EP - 106 PB - American Diabetes Association CY - Alexandria ER -