1,585 results on '"Bergmann, S."'
Search Results
2. Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths
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Iwersen-Bergmann, S., Plattner, S., Hischke, S., Müller, A., Andresen-Streichert, H., Jungen, H., Erb, R., and Beer-Sandner, B.
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- 2021
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3. Post-mortem analysis of prescription opioids—A follow-up examination by LC–MS/MS with focus on fentanyl
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Schönfeld, T., Heinemann, A., Schulz, M., Gradl, G., Andresen-Streichert, H., Müller, A., and Iwersen-Bergmann, S.
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- 2019
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4. P-080: IMPLEMENTATION OF SCREENING TOOL IN SICKLE CELL CLINIC TO IDENTIFY SOCIAL DETERMINANTS OF HEALTH
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PATEL J., MANDAVA M., NOISETTE L., DIAZ C., BORAD A., JACKSON S., and BERGMANN S.
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. The challenge of post-mortem GHB analysis: storage conditions and specimen types are both important
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Kietzerow, J., Otto, B., Wilke, N., Rohde, H., Iwersen-Bergmann, S., and Andresen-Streichert, H.
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- 2020
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6. Helium poisoning: new procedure for sampling and analysis
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Varlet, Vincent, Iwersen-Bergmann, S., Alexandre, M., Cordes, O., Wunder, C., Holz, F., Andresen-Streichert, H., Bevalot, F., Dumestre-Toulet, V., Malbranque, S., Fracasso, T., and Grabherr, S.
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- 2019
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7. Poisoning with paracetamol: Cases from Hamburg and the GIZ Nord Poison Center with special respect to legislation change in 2009 concerning pack sizes
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Aboutara, N., Jungen, H., Schaper, A., Sterneck, M., Püschel, K., and Iwersen-Bergmann, S.
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- 2019
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8. Cocainkonsumintensität als Ursache erworbener Herzerkrankungen?: Korrelationen bei cocainassoziierten Drogentodesfällen
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Muras, L. H., Iwersen-Bergmann, S., Püschel, K., and Heinemann, A.
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- 2019
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9. Net reclassification improvement with serial biomarkers and bed-sided spirometry to early predict the need of organ support during the early post-transplantation in-hospital stay in allogeneic HCT recipients
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Braun, S. D., Kuhn, M., Bergmann, S., Katzke, S., Weise, M., Alakel, N., Stölzel, F., Kroschinsky, F., Ehninger, G., Höffken, G., and Bornhäuser, M.
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- 2019
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10. Mass poisoning with NPS: 2C-E and Bromo-DragonFly
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Iwersen-Bergmann, S., Lehmann, S., Heinemann, A., Schröder, C., Müller, A., Jungen, H., Andresen-Streichert, H., Pueschel, K., Vidal, C., and Mercer-Chalmers-Bender, K.
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- 2019
- Full Text
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11. Status of the solution to the solar neutrino problem based on non-standard neutrino interactions
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Bergmann, S., Guzzo, M. M., de Holanda, P. C., Krastev, P. I., and Nunokawa, H.
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High Energy Physics - Phenomenology - Abstract
We analyze the current status of the solution to the solar neutrino problem based both on: a) non-standard flavor changing neutrino interactions (FCNI) and b) non-universal flavor diagonal neutrino interactions (FDNI). We find that FCNI and FDNI with matter in the sun as well as in the earth provide a good fit not only to the total rate measured by all solar neutrino experiments but also to the day-night and seasonal variations of the event rate, as well as the recoil electron energy spectrum measured by the SuperKamiokande collaboration. This solution does not require massive neutrinos and neutrino mixing in vacuum. Stringent experimental constraints on FCNI from bounds on lepton flavor violating decays and on FDNI from limits on lepton universality violation rule out $\nu_e \to \nu_\mu$ transitions induced by New Physics as a solution to the solar neutrino problem. However, a solution involving $\nu_e \to \nu_\tau$ transitions is viable and could be tested independently by the upcoming $B$-factories if flavor violating tau decays would be observed at a rate close to the present upper bounds., Comment: 30 pages, 9 figures, Latex
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- 2000
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12. Inoculation of cyprinid herpesvirus 3 (CyHV-3) on common carp brain cells—influence of process parameters on virus yield
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Mletzko, A., Amtmann, A., Bergmann, S., Lee, P., Christian, J., Buchholz, R., and Becker, A.
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- 2017
13. 5610845 A PHASE 1 STUDY OF CSL888 (HEMOPEXIN) IN ADULT PATIENTS WITH SICKLE CELL DISEASE
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Biemond, B.J., primary, Shore, B.J., additional, Wilson, F., additional, Jochems, J., additional, Lindqvist, L.M., additional, Jung, K., additional, Gentinetta, T., additional, Costin, S., additional, Kato, G.J., additional, Eleftheriou, P., additional, Fok, H., additional, Wahab, E., additional, Leung, P.M., additional, Sharif, J., additional, Boucher, A., additional, Fitzgerald, R., additional, Keese-Adu, R., additional, Azbell, R., additional, Liles, D., additional, Bergmann, S., additional, Lanzkron, S., additional, and Gordeuk, V., additional
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- 2023
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14. Emulation of control strategies through machine learning in manufacturing simulations
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Bergmann, S, Feldkamp, N, and Strassburger, S
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- 2017
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15. Quick EPD mapping of GaAs
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Donecker, J., primary, Rautenstrauch, S., additional, and Bergmann, S., additional
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- 2017
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16. Chapter 7: Austria
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Bergmann, S., primary
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- 2017
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17. PMD basierte Fahrspurerkennung und -Verfolgung für Fahrerassistenzsysteme
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Gumpp, T., Schamm, T., Bergmann, S., Zöllner, J. M., Dillmann, R., Brauer, W., editor, Berns, Karsten, editor, and Luksch, Tobias, editor
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- 2007
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18. SARS-CoV-2-seronegative subjects target CTL epitopes in the SARS-CoV-2 nucleoprotein cross-reactive to common cold coronaviruses
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Schmidt, K., Nganou-Makamdop, K., Tenbusch, M., El Kenz, B., Maier, C., Lapuente, D., Uberla, K., Spriewald, B., Bergmann, S., Harrer, E.G., and Harrer, T.
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Nucleoproteins -- Health aspects ,T cells -- Genetic aspects -- Health aspects ,Immune response -- Genetic aspects ,Coronaviruses -- Genetic aspects -- Health aspects ,Health - Abstract
Background: The beta-coronavirus SARS-CoV-2 induces severe disease (COVID-19) mainly in elderly persons with risk factors, whereas the majority of patients experience a mild course of infection. As the circulating common [...]
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- 2021
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19. The amino-terminal domain of ORF149 of koi herpesvirus is preferentially targeted by IgM from carp populations surviving infection
- Author
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Torrent, F., Villena, A., Lee, P. A., Fuchs, W., Bergmann, S. M., and Coll, J. M.
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- 2016
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20. Die HIV-spezifische T-Zellantwort
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Harrer, T., Harrer, E., Schmitt, M., Bäuerle, M., Goldwich, A., Grädner, I., Bergmann, S., Kalden, J. R., Brockmeyer, Norbert H., editor, Hoffmann, Klaus, editor, Reimann, G., editor, Stücker, Markus, editor, Altmeyer, Peter, editor, and Brodt, R., editor
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- 2000
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21. Analyse des Methylierungsstatus eines Integrierten HIV-Konstrukts in Zellkultur nach Inaktivierung und nach Reaktivierung
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Marschall, M., Bergmann, S., Fröhlich, U., Löwer, R., Löwer, J., Brockmeyer, Norbert H., editor, Hoffmann, Klaus, editor, Reimann, G., editor, Stücker, Markus, editor, Altmeyer, Peter, editor, and Brodt, R., editor
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- 2000
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22. Copeptin predicts clinical deterioration and persistent instability in community-acquired pneumonia
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Kolditz, M., Halank, M., Schulte-Hubbert, B., Bergmann, S., Albrecht, S., and Höffken, G.
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- 2012
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23. Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs
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Andresen-Streichert, Hilke, Jensen, P., Kietzerow, J., Schrot, M., Wilke, N., Vettorazzi, E., Mueller, A., and Iwersen-Bergmann, S.
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- 2015
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24. Correction to: Mass poisoning with NPS: 2C-E and Bromo-DragonFly
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Iwersen-Bergmann, S., Lehmann, S., Heinemann, A., Schröder, C., Müller, A., Jungen, H., Andresen-Streichert, H., Pueschel, K., Vidal, C., and Mercer-Chalmers-Bender, K.
- Published
- 2019
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25. Optical reconfiguration of surface relief gratings on supramolecular polymer films using grating translation and superposition.
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Krüger, J., Bolle, N., Calvelo, T., Bergmann, S., Abourahma, H., and McGee, D. J.
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SUPRAMOLECULAR polymers ,POLYMER films ,FIREPLACES ,TRANSLATIONS - Abstract
We demonstrate the optical erasure and amplification of surface relief gratings written on supramolecular azobenzene-polymer films. The reversible photomechanical response of azobenzene-polymer films enables surface reconfiguration through grating superposition, which is implemented through mechanical film translation and exposure in a laser interference pattern. Sinusoidal surface relief gratings could be photoerased and regenerated using laser exposures with interference patterns shifted by half a period. Gratings could also be amplified and their surface coverage extended through multiple translations and exposures at integer-period steps. We report the fabrication of a 2.0 × 2.0 mm 2 surface grating of amplitude 697 nm from an initial grating of 78 nm amplitude through raster scanning and reexposing using a step translation equal to 10 fringes. [ABSTRACT FROM AUTHOR]
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- 2019
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26. Influence of smoking and body weight on adipokines in middle aged women
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Bergmann S and Siekmeier R
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smoking ,women ,adipokines ,inflammation ,Medicine - Abstract
Abstract Objective Quitting smoking was associated with an undesirable weight gain. Both, cigarette smoking and obesity were accompanied by subclinical systemic inflammation. This may cause unfavourable changes in (plasma) adipokine concentration. The aim of the present study was to establish the influence of moderate cigarette smoking on the concentration of the adipokines leptin and adiponectin and the pro-inflammatory factors CRP, SAA, IL-6 and TNF-α in non-obese (n = 138) and obese (n = 175) perimenopausal women of the DRECAN-2005 survey. Results Among non-obese women, adiponectin was significantly lower in smokers than in non-smokers (16.88 ± 6.85 vs. 20.63 ± 10.04 μg/ml; P < 0.05). Leptin tended to lower values, too. Among obese women, none significant differences in adiponectin or leptin concentration were observed between smokers and non-smokers. In obese smokers and obese non-smokers, the adiponectin concentrations were significantly lower and the leptin concentrations were significantly higher than in non-obese non-smokers. Non-obese smokers showed significantly higher leukocyte count (6.50 ± 1.83 vs. 5.51 ± 1.31 GPT/l; P < 0.001) and serum amyloid A concentration (7.81 ± 1.25 vs. 4.22 ± 1.43 mg/l; P < 0.05) than non-obese non-smokers. There were only tendencies to higher concentration of CRP, IL-6, and TNF-α. In obese women, moderate cigarette smoking was not associated with higher leukocyte count or concentration of SAA. Among non-smokers, overweight was associated higher concentration of leptin (22.16 ± 12.16 vs. 11.49 ± 6.37 ng/ml; P < 0.001) and with significantly lower concentration of adiponectin (16.29 ± 8.01 vs. 20.77 ± 9.99 μg/ml; P < 0.001). Among smokers, overweight was associated with higher leptin concentration only (obese: 18.62 ± 13.46 vs. non-obese: 8.84 ± 4.92 ng/ml; P < 0.01). Conclusions In non-obese middle aged women, even moderate cigarette smoking adversely influences the serum concentration of adiponectin and SAA. Over-weight hides possible effects of smoking on cytokines and adipokines.
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- 2009
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27. Pharmakokinetische Wechselwirkungen illegaler Drogen mit Arzneimitteln
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Keil, S., Iwersen-Bergmann, S., Müller, A., and Andresen-Streichert, H.
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- 2014
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28. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity
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Frkjær, J. B., Bergmann, S., Brock, C., Madzak, A., Farmer, A. D., Ellrich, J., and Drewes, A. M.
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- 2016
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29. Lp(a)-Verteilung in der Dresdener Bevölkerung — DRECAN-Studie
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Bergmann, S., Freidt, T., Jaroß, W., Schottmann, B., Siegert, G., Thulin, H., Assmann, G., Heinrich, J., Sandkamp, M., Epping, P. H., Martin, H., Petersen, G., Schulte, H., Wahrburg, U., Heinle, H., editor, Schulte, H., editor, and Schaefer, H. E., editor
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- 1993
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30. KHK-Risikoprofil der arbeitenden Bevölkerung im Raum Dresden ein Jahr nach der 'Wende', (DRECAN-Studie)
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DRECAN-Team, Jaroß, W., Schulte, H., Bergmann, S., Assmann, G., Freidt, T., Schottmann, B., Siegert, G., Thulin, H., Epping, P. H., Heinrich, J., Martin, H., Petersen, S., Sandkamp, M., Wahrburg, U., Heinle, H., editor, Schulte, H., editor, and Schaefer, H. E., editor
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- 1993
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31. The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression
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Samaan, Z, Anand, S, Zhang, X, Desai, D, Rivera, M, Pare, G, Thabane, L, Xie, C, Gerstein, H, Engert, J C, Craig, I, Cohen-Woods, S, Mohan, V, Diaz, R, Wang, X, Liu, L, Corre, T, Preisig, M, Kutalik, Z, Bergmann, S, Vollenweider, P, Waeber, G, Yusuf, S, and Meyre, D
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- 2013
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32. Assessment of network module identification across complex diseases
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Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Marbach, D, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, W, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Choobdar S., Ahsen M. E., Crawford J., Tomasoni M., Fang T., Lamparter D., Lin J., Hescott B., Hu X., Mercer J., Natoli T., Narayan R., Aicheler F., Amoroso N., Arenas A., Azhagesan K., Baker A., Banf M., Batzoglou S., Baudot A., Bellotti R., Bergmann S., Boroevich K. A., Brun C., Cai S., Caldera M., Calderone A., Cesareni G., Chen W., Chichester C., Cowen L., Cui H., Dao P., De Domenico M., Dhroso A., Didier G., Divine M., del Sol A., Feng X., Flores-Canales J. C., Fortunato S., Gitter A., Gorska A., Guan Y., Guenoche A., Gomez S., Hamza H., Hartmann A., He S., Heijs A., Heinrich J., Hu Y., Huang X., Hughitt V. K., Jeon M., Jeub L., Johnson N. T., Joo K., Joung I. S., Jung S., Kalko S. G., Kamola P. J., Kang J., Kaveelerdpotjana B., Kim M., Kim Y. -A., Kohlbacher O., Korkin D., Krzysztof K., Kunji K., Kutalik Z., Lage K., Lang-Brown S., Le T. D., Lee J., Lee S., Li D., Li J., Liu L., Loizou A., Luo Z., Lysenko A., Ma T., Mall R., Marbach D., Mattia T., Medvedovic M., Menche J., Micarelli E., Monaco A., Muller F., Narykov O., Norman T., Park S., Perfetto L., Perrin D., Pirro S., Przytycka T. M., Qian X., Raman K., Ramazzotti D., Ramsahai E., Ravindran B., Rennert P., Saez-Rodriguez J., Scharfe C., Sharan R., Shi N., Shin W., Shu H., Sinha H., Slonim D. K., Spinelli L., Srinivasan S., Subramanian A., Suver C., Szklarczyk D., Tangaro S., Thiagarajan S., Tichit L., Tiede T., Tripathi B., Tsherniak A., Tsunoda T., Turei D., Ullah E., Vahedi G., Valdeolivas A., Vivek J., von Mering C., Waagmeester A., Wang B., Wang Y., Weir B. A., White S., Winkler S., Xu K., Xu T., Yan C., Yang L., Yu K., Yu X., Zaffaroni G., Zaslavskiy M., Zeng T., Zhang J. D., Zhang L., Zhang W., Zhang X., Zhang J., Zhou X., Zhou J., Zhu H., Zhu J., Zuccon G., Stolovitzky G., Cowen L. J., Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Marbach, D, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, W, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Choobdar S., Ahsen M. E., Crawford J., Tomasoni M., Fang T., Lamparter D., Lin J., Hescott B., Hu X., Mercer J., Natoli T., Narayan R., Aicheler F., Amoroso N., Arenas A., Azhagesan K., Baker A., Banf M., Batzoglou S., Baudot A., Bellotti R., Bergmann S., Boroevich K. A., Brun C., Cai S., Caldera M., Calderone A., Cesareni G., Chen W., Chichester C., Cowen L., Cui H., Dao P., De Domenico M., Dhroso A., Didier G., Divine M., del Sol A., Feng X., Flores-Canales J. C., Fortunato S., Gitter A., Gorska A., Guan Y., Guenoche A., Gomez S., Hamza H., Hartmann A., He S., Heijs A., Heinrich J., Hu Y., Huang X., Hughitt V. K., Jeon M., Jeub L., Johnson N. T., Joo K., Joung I. S., Jung S., Kalko S. G., Kamola P. J., Kang J., Kaveelerdpotjana B., Kim M., Kim Y. -A., Kohlbacher O., Korkin D., Krzysztof K., Kunji K., Kutalik Z., Lage K., Lang-Brown S., Le T. D., Lee J., Lee S., Li D., Li J., Liu L., Loizou A., Luo Z., Lysenko A., Ma T., Mall R., Marbach D., Mattia T., Medvedovic M., Menche J., Micarelli E., Monaco A., Muller F., Narykov O., Norman T., Park S., Perfetto L., Perrin D., Pirro S., Przytycka T. M., Qian X., Raman K., Ramazzotti D., Ramsahai E., Ravindran B., Rennert P., Saez-Rodriguez J., Scharfe C., Sharan R., Shi N., Shin W., Shu H., Sinha H., Slonim D. K., Spinelli L., Srinivasan S., Subramanian A., Suver C., Szklarczyk D., Tangaro S., Thiagarajan S., Tichit L., Tiede T., Tripathi B., Tsherniak A., Tsunoda T., Turei D., Ullah E., Vahedi G., Valdeolivas A., Vivek J., von Mering C., Waagmeester A., Wang B., Wang Y., Weir B. A., White S., Winkler S., Xu K., Xu T., Yan C., Yang L., Yu K., Yu X., Zaffaroni G., Zaslavskiy M., Zeng T., Zhang J. D., Zhang L., Zhang W., Zhang X., Zhang J., Zhou X., Zhou J., Zhu H., Zhu J., Zuccon G., Stolovitzky G., and Cowen L. J.
- Abstract
Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the ‘Disease Module Identification DREAM Challenge’, an open competition to comprehensively assess module identification methods across diverse protein–protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.
- Published
- 2019
33. Gamma-Hydroxybutyrate in Urine and Serum: Additional Data Supporting Current Cut-Off Recommendations
- Author
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Andresen, H., Sprys, N., Schmoldt, A., Mueller, A., and Iwersen-Bergmann, S.
- Published
- 2010
- Full Text
- View/download PDF
34. Targeting glioblastoma using a novel peptide specific to a deglycosylated isoform of brevican
- Author
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von Spreckelsen, N, Fadzen, CM, Hartrampf, N, Ghotmi, Y, Wolfe, J, Dubey, S, Yang, BY, Kijewski, M, Wang, S, Farquhar, C, Bergmann, S, Zdioruk, M, Wasserburg, JR, Murrell, E, Bononi, FC, Luyt, LG, Di Carli, M, Lamfers, MLM, Ligon, KL, Chiocca, EA, Viapiano, MS, Pentelute, BL, Lawler, SE, and Cho, CF
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine ,nervous system diseases - Abstract
Objective: Glioblastoma (GBM) is the most common and deadliest form of brain tumor and treatment options available today have limited success. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie
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- 2021
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35. Biological Properties of Hybrid Plasminogen Activators
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Hung, P. P., Wilhelm, J., Kalyan, N. K., Cheng, S. M., Lee, S. G., James, H. L., Nachowiak, D., Weinheimer, C. J., Sobel, B. E., Bergmann, S. R., Liu, Chung Yuan, editor, and Chien, Shu, editor
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- 1990
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36. Corrigendum to “Investigation of the occurrence of pathological carcass alterations at the processing plant in meat turkeys reared in organic production systems in Germany”
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Freihold, D., primary, Bartels, T., additional, Bergmann, S., additional, Berk, J., additional, Deerberg, F., additional, Dressel, A., additional, Erhard, M.H., additional, Ermakow, O., additional, Huchler, M., additional, Spindler, B., additional, Thieme, S., additional, Krautwald-Junghanns, M.-E., additional, and Hafez, H.M., additional
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- 2021
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37. Comparison of Risk Factors for Coronary Heart Disease in Dresden and Münster: Results of the DRECAN (Dresden Cardiovascular Risk and Nutrition) Study and the PROCAM (Prospective Cardiovascular Münster) Study
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Jaross, W., Assmann, G., Bergmann, S., and Schulte, H.
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- 1994
38. Investigation of the occurrence of pathological carcass alterations at the processing plant in meat turkeys reared in organic production systems in Germany
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Freihold, D., primary, Bartels, T., additional, Bergmann, S., additional, Berk, J., additional, Deerberg, F., additional, Dressel, A., additional, Erhard, M.H., additional, Ermakow, O., additional, Huchler, M., additional, Spindler, B., additional, Thieme, S., additional, Krautwald-Junghanns, M.-E., additional, and Hafez, H.M., additional
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- 2021
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39. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
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Vosa, U. (Urmo), Claringbould, A. (Annique), Westra, H.-J. (Harm-Jan), Bonder, M. J. (Marc Jan), Deelen, P. (Patrick), Zeng, B. (Biao), Kirsten, H. (Holger), Saha, A. (Ashis), Kreuzhuber, R. (Roman), Yazar, S. (Seyhan), Brugge, H. (Harm), Oelen, R. (Roy), de Vries, D. H. (Dylan H.), van der Wijst, M. G. (Monique G. P.), Kasela, S. (Silva), Pervjakova, N. (Natalia), Alves, I. (Isabel), Fave, M.-J. (Marie-Julie), Agbessi, M. (Mawusse), Christiansen, M. W. (Mark W.), Jansen, R. (Rick), Seppala, I. (Ilkka), Tong, L. (Lin), Teumer, A. (Alexander), Schramm, K. (Katharina), Hemani, G. (Gibran), Verlouw, J. (Joost), Yaghootkar, H. (Hanieh), Flitman, R. S. (Reyhan Sonmez), Brown, A. (Andrew), Kukushkina, V. (Viktorija), Kalnapenkis, A. (Anette), Rueger, S. (Sina), Porcu, E. (Eleonora), Kronberg, J. (Jaanika), Kettunen, J. (Johannes), Lee, B. (Bernett), Zhang, F. (Futao), Qi, T. (Ting), Hernandez, J. A. (Jose Alquicira), Arindrarto, W. (Wibowo), Beutner, F. (Frank), Dmitrieva, J. (Julia), Elansary, M. (Mahmoud), Fairfax, B. P. (Benjamin P.), Georges, M. (Michel), Heijmans, B. T. (Bastiaan T.), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Kim, Y. (Yungil), Knight, J. C. (Julian C.), Kovacs, P. (Peter), Krohn, K. (Knut), Li, S. (Shuang), Loeffler, M. (Markus), Marigorta, U. M. (Urko M.), Mei, H. (Hailang), Momozawa, Y. (Yukihide), Mueller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. G. (Michel G.), Penninx, B. W. (Brenda W. J. H.), Pritchard, J. K. (Jonathan K.), Raitakari, O. T. (Olli T.), Rotzschke, O. (Olaf), Slagboom, E. P. (Eline P.), Stehouwer, C. D. (Coen D. A.), Stumvoll, M. (Michael), Sullivan, P. (Patrick), Thiery, J. (Joachim), Tonjes, A. (Anke), van Dongen, J. (Jenny), van Iterson, M. (Maarten), Veldink, J. H. (Jan H.), Voelker, U. (Uwe), Warmerdam, R. (Robert), Wijmenga, C. (Cisca), Swertz, M. (Morris), Andiappan, A. (Anand), Montgomery, G. W. (Grant W.), Ripatti, S. (Samuli), Perola, M. (Markus), Kutalik, Z. (Zoltan), Dermitzakis, E. (Emmanouil), Bergmann, S. (Sven), Frayling, T. (Timothy), van Meurs, J. (Joyce), Prokisch, H. (Holger), Ahsan, H. (Habibul), Pierce, B. L. (Brandon L.), Lehtimaki, T. (Terho), Boomsma, D. I. (Dorret, I), Psaty, B. M. (Bruce M.), Gharib, S. A. (Sina A.), Awadalla, P. (Philip), Milani, L. (Lili), Ouwehand, W. H. (Willem H.), Downes, K. (Kate), Stegle, O. (Oliver), Battle, A. (Alexis), Visscher, P. M. (Peter M.), Yang, J. (Jian), Scholz, M. (Markus), Powell, J. (Joseph), Gibson, G. (Greg), Esko, T. (Tonu), and Franke, L. (Lude)
- Abstract
Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.
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- 2021
40. Genetic Dissection of the Regulatory Mechanisms of Ace2 in the Infected Mouse Lung
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Cui, Y., Lu, L., Gao, J., Sims, A.C., Ashbrook, D.G., Bergmann, S., Schughart, K., Li, K., Xu, F., Baric, R.S., Williams, R.W., and Jonsson, C.B.
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viruses - Abstract
Acute lung injury (ALI) is an important cause of morbidity and mortality after viral infections, including influenza A virus H1N1, SARS-CoV, MERS-CoV, and SARS-CoV-2. The angiotensin I converting enzyme 2 (ACE2) is a key host membrane-bound protein that modulates ALI induced by viral infection, pulmonary acid aspiration, and sepsis. However, the contributions of ACE2 sequence variants to individual differences in disease risk and severity after viral infection are not understood. In this study, we quantified H1N1 influenza-infected lung transcriptomes across a family of 41 BXD recombinant inbred strains of mice and both parents—C57BL/6J and DBA/2J. In response to infection Ace2 mRNA levels decreased significantly for both parental strains and the expression levels was associated with disease severity (body weight loss) and viral load (expression levels of viral NA segment) across the BXD family members. Pulmonary RNA-seq for 43 lines was analyzed using weighted gene co-expression network analysis (WGCNA) and Bayesian network approaches. Ace2 not only participated in virus-induced ALI by interacting with TNF, MAPK, and NOTCH signaling pathways, but was also linked with high confidence to gene products that have important functions in the pulmonary epithelium, including Rnf128, Muc5b, and Tmprss2. Comparable sets of transcripts were also highlighted in parallel studies of human SARS-CoV-infected primary human airway epithelial cells. Using conventional mapping methods, we determined that weight loss at two and three days after viral infection maps to chromosome X—the location of Ace2. This finding motivated the hierarchical Bayesian network analysis, which defined molecular endophenotypes of lung infection linked to Ace2 expression and to a key disease outcome. Core members of this Bayesian network include Ace2, Atf4, Csf2, Cxcl2, Lif, Maml3, Muc5b, Reg3g, Ripk3, and Traf3. Collectively, these findings define a causally-rooted Ace2 modulatory network relevant to host response to viral infection and identify potential therapeutic targets for virus-induced respiratory diseases, including those caused by influenza and coronaviruses.
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- 2021
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41. Genetic insights into biological mechanisms governing human ovarian ageing.
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Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., Perry J.R.B., Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., and Perry J.R.B.
- Abstract
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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- 2021
42. Genetic insights into biological mechanisms governing human ovarian ageing
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Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, Perry, JRB, Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, and Perry, JRB
- Abstract
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
- Published
- 2021
43. The trans-ancestral genomic architecture of glycemic traits
- Author
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Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), Barroso, I. (Ines), Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), and Barroso, I. (Ines)
- Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
- Published
- 2021
44. The trans-ancestral genomic architecture of glycemic traits
- Author
-
Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), Tremoli E., Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), and Tremoli E.
- Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
- Published
- 2021
45. Statistical mediation of the relationships between chronological age and lipoproteins by nonessential amino acids in healthy men
- Author
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Universitat Rovira i Virgili, Mallol R; Vallvé JC; Solà R; Girona J; Bergmann S; Correig X; Rock E; Winklhofer-Roob BM; Rehues P; Guardiola M; Masana L; Ribalta J, Universitat Rovira i Virgili, and Mallol R; Vallvé JC; Solà R; Girona J; Bergmann S; Correig X; Rock E; Winklhofer-Roob BM; Rehues P; Guardiola M; Masana L; Ribalta J
- Abstract
Aging is a major risk factor for metabolic impairment that may lead to age-related diseases such as cardiovascular disease. Different mechanisms that may explain the interplay between aging and lipoproteins, and between aging and low-molecular-weight metabolites (LMWMs), in the metabolic dysregulation associated with age-related diseases have been described separately. Here, we statistically evaluated the possible mediation effects of LMWMs on the relationships between chronological age and lipoprotein concentrations in healthy men ranging from 19 to 75 years of age. Relative and absolute concentrations of LMWMs and lipoproteins, respectively, were assessed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate linear regression and mediation analysis were conducted to explore the associations between age, lipoproteins and LMWMs. The statistical significance of the identified mediation effects was evaluated using the bootstrapping technique, and the identified mediation effects were validated on a publicly available dataset. Chronological age was statistically associated with five lipoprotein classes and subclasses. The mediation analysis showed that serine mediated 24.1% (95% CI: 22.9 – 24.7) of the effect of age on LDL-P, and glutamate mediated 17.9% (95% CI: 17.6 – 18.5) of the effect of age on large LDL-P. In the publicly available data, glutamate mediated the relationship between age and an NMR-derived surrogate of cholesterol. Our results suggest that the age-related increase in LDL particles may be mediated by a decrease in the nonessential amino acid glutamate. Future studies may contribute to a better understanding of the potential biological role of glutamate and LDL particles in aging mechanisms and age-related diseases. © 2021 The Authors
- Published
- 2021
46. Depressive disorder moderates the effect of the FTO gene on body mass index
- Author
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Rivera, M, Cohen-Woods, S, Kapur, K, Breen, G, Ng, M Y, Butler, A W, Craddock, N, Gill, M, Korszun, A, Maier, W, Mors, O, Owen, M J, Preisig, M, Bergmann, S, Tozzi, F, Rice, J, Rietschel, M, Rucker, J, Schosser, A, Aitchison, K J, Uher, R, Craig, I W, Lewis, C M, Farmer, A E, and McGuffin, P
- Published
- 2012
- Full Text
- View/download PDF
47. Supplement to: Carotid intima-media thickness and cardiovascular events.
- Author
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Inaba, Y, Chen, J A, and Bergmann, S R
- Published
- 2011
48. Age-dependent baseline values of faecal cortisol metabolites in the American mink (Neovison vison) under semi-natural housing conditions
- Author
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Rauch, E., Bergmann, S., Hagn, A., Meixensperger, J., Reese, S., Palme, R., and Erhard, M. H.
- Published
- 2014
- Full Text
- View/download PDF
49. Ältere Menschen und psychotrope Substanzen im Straßenverkehr
- Author
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Iwersen-Bergmann, S., Andresen, H., Püschel, K., Heinemann , A., and von Renteln-Kruse, W.
- Published
- 2009
- Full Text
- View/download PDF
50. Kontroverse der tödlichen Monointoxikationen mit Flunitrazepam
- Author
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Kaiser, C., Iwersen-Bergmann, S., and Kauert, G.
- Published
- 2009
- Full Text
- View/download PDF
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