Janine Kroeger, Karina Meidtner, Norbert Stefan, Marcela Guevara, Nicola D. Kerrison, Eva Ardanaz, Dagfinn Aune, Heiner Boeing, Miren Dorronsoro, Courtney Dow, Guy Fagherazzi, Paul W. Franks, Heinz Freisling, Marc J. Gunter, Jose Maria Huerta, Rudolf Kaaks, Timothy J. Key, Kay Tee Khaw, Vittorio Krogh, Tilman Kuehn, Francesca Romana Mancini, Amalia Mattiello, Peter M. Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, J. Ramon Quiros, Olov Rolandsson, Carlotta Sacerdote, Nuria Sala, Elena Salamanca-Fernandez, Ivonne Sluijs, Annemieke M. W. Spijkerman, Anne Tjonneland, Konstantinos K. Tsilidis, Rosario Tumino, Yvonne T. van der Schouw, Nita G. Forouhi, Stephen J. Sharp, Claudia Langenberg, Elio Riboli, Matthias Bernd Schulze, Nicholas J. Wareham
- Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with thoseFetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.…
MetadatenAuthor details: | Janine Kroeger, Karina Meidtner, Norbert StefanORCiD, Marcela GuevaraORCiD, Nicola D. Kerrison, Eva Ardanaz, Dagfinn AuneORCiD, Heiner BoeingORCiDGND, Miren Dorronsoro, Courtney Dow, Guy FagherazziORCiD, Paul W. Franks, Heinz FreislingORCiD, Marc J. Gunter, Jose Maria Huerta, Rudolf Kaaks, Timothy J. Key, Kay Tee Khaw, Vittorio KroghORCiD, Tilman Kuehn, Francesca Romana ManciniORCiD, Amalia Mattiello, Peter M. Nilsson, Anja Olsen, Kim OvervadORCiD, Domenico Palli, J. Ramon Quiros, Olov Rolandsson, Carlotta Sacerdote, Nuria SalaORCiD, Elena Salamanca-FernandezORCiD, Ivonne Sluijs, Annemieke M. W. Spijkerman, Anne Tjonneland, Konstantinos K. Tsilidis, Rosario Tumino, Yvonne T. van der Schouw, Nita G. Forouhi, Stephen J. Sharp, Claudia LangenbergORCiD, Elio RiboliORCiD, Matthias Bernd SchulzeORCiDGND, Nicholas J. Wareham |
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DOI: | https://doi.org/10.2337/db17-1268 |
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ISSN: | 0012-1797 |
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ISSN: | 1939-327X |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29523632 |
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Title of parent work (English): | Diabetes : a journal of the American Diabetes Association |
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Subtitle (English): | a mendelian randomization analysis |
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Publisher: | American Diabetes Association |
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Place of publishing: | Alexandria |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/05/21 |
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Publication year: | 2018 |
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Release date: | 2021/11/22 |
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Volume: | 67 |
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Issue: | 6 |
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Number of pages: | 6 |
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First page: | 1200 |
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Last Page: | 1205 |
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Funding institution: | European UnionEuropean Union (EU) [LSHM_CT_2006_037197]; German Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF); State of Brandenburg; Regional Government of Navarre; Instituto de Salud Carlos IIIInstituto de Salud Carlos III [PIE14/00045]; Health Research Fund (FIS) of the Spanish Ministry of HealthInstituto de Salud Carlos III; Navarre Regional Government; Swedish Research CouncilSwedish Research Council; Novo NordiskNovo Nordisk; Swedish Diabetes Association; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Spanish Ministry of Health, Murcia Regional Government [6236]; German Cancer AidDeutsche Krebshilfe; BMBFFederal Ministry of Education & Research (BMBF); Cancer Research UKCancer Research UK [C8221/A19170]; Medical Research CouncilMedical Research Council UK (MRC) [MR/M012190/1]; Medical Research CouncilMedical Research Council UK (MRC); Cancer Research UKCancer Research UK; German Cancer Research Center (DKFZ)Helmholtz Association; Danish Cancer SocietyDanish Cancer Society; Regional Government of Asturias; Vasterboten County Council; Spanish Ministry of Health network RTICCC (ISCIII) [RD12/0036/0018]; FEDER funds/European Regional Development Fund (ERDF)European Union (EU); Generalitat de CatalunyaGeneralitat de Catalunya [AGAUR 2014SGR726]; Dutch Ministry of Health, Welfare and Sport; Netherlands Cancer Registry; LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland)Netherlands Organization for Scientific Research (NWO); World Cancer Research Fund (WCRF)World Cancer Research Fund International (WCRF); Statistics Netherlands; NL Agency [IGE05012]; Board of the University Medical Center Utrecht; VWS Research Fund; NKR Research Fund; Utilita Sociale; Imperial College Biomedical Research Centre |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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