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1. Role of human plasma metabolites in prediabetes and type 2 diabetes from the IMI-DIRECT study

Author

Sharma, Sapna, Dong, Qiuling, Haid, Mark, Adam, Jonathan, Bizzotto, Roberto, Fernandez-Tajes, Juan J., Jones, Angus G., Tura, Andrea, Artati, Anna, Prehn, Cornelia, Kastenmüller, Gabi, Koivula, Robert W., Franks, Paul W., Walker, Mark, Forgie, Ian M., Giordano, Giuseppe, Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Manolis, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Tsirigos, Konstantinos D., De Masi, Federico, Brunak, Soren, Viñuela, Ana, Mari, Andrea, McDonald, Timothy J., Kokkola, Tarja, Adamski, Jerzy, Pearson, Ewan R., and Grallert, Harald

Published
2024
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5. A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes

Author

Halama, Anna, Zaghlool, Shaza, Thareja, Gaurav, Kader, Sara, Al Muftah, Wadha, Mook-Kanamori, Marjonneke, Sarwath, Hina, Mohamoud, Yasmin Ali, Stephan, Nisha, Ameling, Sabine, Pucic Baković, Maja, Krumsiek, Jan, Prehn, Cornelia, Adamski, Jerzy, Schwenk, Jochen M., Friedrich, Nele, Völker, Uwe, Wuhrer, Manfred, Lauc, Gordan, Najafi-Shoushtari, S. Hani, Malek, Joel A., Graumann, Johannes, Mook-Kanamori, Dennis, Schmidt, Frank, and Suhre, Karsten

Published
2024
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10. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts

Author

Rothwell, Joseph A., Bešević, Jelena, Dimou, Niki, Breeur, Marie, Murphy, Neil, Jenab, Mazda, Wedekind, Roland, Viallon, Vivian, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Scalbert, Augustin, Huybrechts, Inge, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J., Keun, Hector, Chadeau-Hyam, Marc, Boutron-Ruault, Marie-Christine, Overvad, Kim, Dahm, Christina C., Nøst, Therese Haugdahl, Sandanger, Torkjel M., Skeie, Guri, Zamora-Ros, Raul, Tsilidis, Kostas K., Eichelmann, Fabian, Schulze, Matthias B., van Guelpen, Bethany, Vidman, Linda, Sánchez, Maria-José, Amiano, Pilar, Ardanaz, Eva, Smith-Byrne, Karl, Travis, Ruth, Katzke, Verena, Kaaks, Rudolf, Derksen, Jeroen W. G., Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Palli, Domenico, Pasanisi, Fabrizio, Eriksen, Anne Kirstine, Tjønneland, Anne, Severi, Gianluca, and Gunter, Marc J.

Published
2023
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11. Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author

Harewood, Rhea, Rothwell, Joseph A., Bešević, Jelena, Viallon, Vivian, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Wedekind, Roland, Prehn, Cornelia, Adamski, Jerzy, Schmidt, Julie A., Jacobs, Inarie, Tjønneland, Anne, Olsen, Anja, Severi, Gianluca, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B., Prada, Marcela, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Sacerdote, Carlotta, Jakszyn, Paula Gabriela, Sánchez, Maria-Jose, Castilla, Jesús, Chirlaque, María-Dolores, Atxega, Amaia Aizpurua, van Guelpen, Bethany, Heath, Alicia K., Papier, Keren, Tong, Tammy Y.N., Summers, Scott A., Playdon, Mary, Cross, Amanda J., Keski-Rahkonen, Pekka, Chajès, Véronique, Murphy, Neil, and Gunter, Marc J.

Published
2024
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13. International Ring Trial of a High Resolution Targeted Metabolomics and Lipidomics Platform for Serum and Plasma Analysis

Author

Thompson, J Will, Adams, Kendra J, Adamski, Jerzy, Asad, Yasmin, Borts, David, Bowden, John A, Byram, Gregory, Dang, Viet, Dunn, Warwick B, Fernandez, Facundo, Fiehn, Oliver, Gaul, David A, Hühmer, Andreas FR, Kalli, Anastasia, Koal, Therese, Koeniger, Stormy, Mandal, Rupasri, Meier, Florian, Naser, Fuad J, O’Neil, Donna, Pal, Akos, Patti, Gary J, Pham-Tuan, Hai, Prehn, Cornelia, Raynaud, Florence I, Shen, Tong, Southam, Andrew D, St. John-Williams, Lisa, Sulek, Karolina, Vasilopoulou, Catherine G, Viant, Mark, Winder, Catherine L, Wishart, David, Zhang, Lun, Zheng, Jiamin, and Moseley, M Arthur

Subjects
Amino Acids, Analysis of Variance, Animals, Biogenic Amines, Blood Chemical Analysis, Chromatography, High Pressure Liquid, Data Aggregation, Female, Humans, Limit of Detection, Lipidomics, Lipids, Male, Mass Spectrometry, Metabolome, Metabolomics, Mice, Rats, Reproducibility of Results, Analytical Chemistry, Other Chemical Sciences
Abstract

A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantitative metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with the Biocrates AbsoluteIDQ p400HR kit, to quantify up to 408 metabolites. The specimens included human plasma and serum from male and female donors, mouse and rat plasma, as well as NIST SRM 1950 reference plasma. The metabolite classes covered range from polar (e.g., amino acids and biogenic amines) to nonpolar (e.g., diacyl- and triacyl-glycerols), and they span 11 common metabolite classes. The manuscript describes a strict system suitability testing (SST) criteria used to evaluate each laboratory's readiness to perform the assay, and provides the SST Skyline documents for public dissemination. The study found approximately 250 metabolites were routinely quantified in the sample types tested, using Orbitrap instruments. Interlaboratory variance for the NIST SRM-1950 has a median of 10% for amino acids, 24% for biogenic amines, 38% for acylcarnitines, 25% for glycerolipids, 23% for glycerophospholipids, 16% for cholesteryl esters, 15% for sphingolipids, and 9% for hexoses. Comparing to consensus values for NIST SRM-1950, nearly 80% of comparable analytes demonstrated bias of

Published
2019

14. Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort

Author

Rothwell, Joseph A., Murphy, Neil, Bešević, Jelena, Kliemann, Nathalie, Jenab, Mazda, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Vozar, Béatrice, Scalbert, Augustin, Huybrechts, Inge, Freisling, Heinz, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J., Pala, Valeria Maria, Boutron-Ruault, Marie-Christine, Dahm, Christina C., Overvad, Kim, Gram, Inger Torhild, Sandanger, Torkjel M., Skeie, Guri, Jakszyn, Paula, Tsilidis, Kostas K., Aleksandrova, Krasimira, Schulze, Matthias B., Hughes, David J., van Guelpen, Bethany, Bodén, Stina, Sánchez, Maria-José, Schmidt, Julie A., Katzke, Verena, Kühn, Tilman, Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Masala, Giovanna, Panico, Salvatore, Eriksen, Anne Kirstine, Tjønneland, Anne, Aune, Dagfinn, Weiderpass, Elisabete, Severi, Gianluca, Chajès, Véronique, and Gunter, Marc J.

Published
2022
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15. The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.

Author

Eriksen, Rebeca, White, Margaret C, Dawed, Adem Y, Perez, Isabel Garcia, Posma, Joram M, Haid, Mark, Sharma, Sapna, Prehn, Cornelia, Thomas, E Louise, Koivula, Robert W, Bizzotto, Roberto, Mari, Andrea, Giordano, Giuseppe N, Pavo, Imre, Schwenk, Jochen M, Masi, Federico De, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, and Mahajan, Anubha

Subjects
TYPE 2 diabetes, PEOPLE with diabetes, MULTIPLE regression analysis, INSULIN resistance, FOOD consumption
Abstract

Context The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood. Objective We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. Methods We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D. Results Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes. Conclusion These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

Author

Wesolowska-Andersen, Agata, Brorsson, Caroline A., Bizzotto, Roberto, Mari, Andrea, Tura, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Prehn, Cornelia, Artati, Anna, Hong, Mun-Gwan, Musholt, Petra B., Kurbasic, Azra, De Masi, Federico, Tsirigos, Kostas, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Thomas, Cecilia Engel, Banasik, Karina, Jennison, Chrisopher, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, Louise, Frost, Gary, Thomsen, Henrik, Allin, Kristine, Hansen, Tue Haldor, Vestergaard, Henrik, Hansen, Torben, Rutters, Femke, Elders, Petra, t’Hart, Leen, Bonnefond, Amelie, Canouil, Mickaël, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Hattersley, Andrew, McDonald, Timothy, Teare, Harriet, Ridderstrale, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Froguel, Philippe, Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, Pearson, Ewan, McCarthy, Mark I., and Brunak, Søren

Published
2022
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17. Pre- versus post-operative untargeted plasma nuclear magnetic resonance spectroscopy metabolomics of pheochromocytoma and paraganglioma

Author

Bliziotis, Nikolaos G., Kluijtmans, Leo A. J., Soto, Sebastian, Tinnevelt, Gerjen H., Langton, Katharina, Robledo, Mercedes, Pamporaki, Christina, Engelke, Udo F. H., Erlic, Zoran, Engel, Jasper, Deutschbein, Timo, Nölting, Svenja, Prejbisz, Aleksander, Richter, Susan, Prehn, Cornelia, Adamski, Jerzy, Januszewicz, Andrzej, Reincke, Martin, Fassnacht, Martin, Eisenhofer, Graeme, Beuschlein, Felix, Kroiss, Matthias, Wevers, Ron A., Jansen, Jeroen J., Deinum, Jaap, and Timmers, Henri J. L. M.

Published
2022
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21. Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk:a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author

Harewood, Rhea, Rothwell, Joseph A, Bešević, Jelena, Viallon, Vivian, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Wedekind, Roland, Prehn, Cornelia, Adamski, Jerzy, Schmidt, Julie A, Jacobs, Inarie, Tjønneland, Anne, Olsen, Anja, Severi, Gianluca, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B, Prada, Marcela, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Sacerdote, Carlotta, Jakszyn, Paula Gabriela, Sánchez, Maria-Jose, Castilla, Jesús, Chirlaque, María-Dolores, Atxega, Amaia Aizpurua, van Guelpen, Bethany, Heath, Alicia K, Papier, Keren, Tong, Tammy Y N, Summers, Scott A, Playdon, Mary, Cross, Amanda J, Keski-Rahkonen, Pekka, Chajès, Véronique, Murphy, Neil, Gunter, Marc J, Harewood, Rhea, Rothwell, Joseph A, Bešević, Jelena, Viallon, Vivian, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Wedekind, Roland, Prehn, Cornelia, Adamski, Jerzy, Schmidt, Julie A, Jacobs, Inarie, Tjønneland, Anne, Olsen, Anja, Severi, Gianluca, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B, Prada, Marcela, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Sacerdote, Carlotta, Jakszyn, Paula Gabriela, Sánchez, Maria-Jose, Castilla, Jesús, Chirlaque, María-Dolores, Atxega, Amaia Aizpurua, van Guelpen, Bethany, Heath, Alicia K, Papier, Keren, Tong, Tammy Y N, Summers, Scott A, Playdon, Mary, Cross, Amanda J, Keski-Rahkonen, Pekka, Chajès, Véronique, Murphy, Neil, and Gunter, Marc J

Abstract

Background Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. Interpretation Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed ass, BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.METHODS: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.INTERPRETATION: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations.F

Published
2024

23. Functional changes of the liver in the absence of growth hormone (GH) action – Proteomic and metabolomic insights from a GH receptor deficient pig model

Author

Riedel, Evamaria O., Hinrichs, Arne, Kemter, Elisabeth, Dahlhoff, Maik, Backman, Mattias, Rathkolb, Birgit, Prehn, Cornelia, Adamski, Jerzy, Renner, Simone, Blutke, Andreas, de Angelis, Martin Hrabĕ, Bidlingmaier, Martin, Schopohl, Jochen, Arnold, Georg J., Fröhlich, Thomas, and Wolf, Eckhard

Published
2020
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24. Corrigendum to “Longitudinal associations between metabolites and immediate, short- and medium-term exposure to ambient air pollution: Results from the KORA cohort study” [Sci. Total Environ. 900 (2023) 165780]

Author

Yao, Yueli, primary, Schneider, Alexandra, additional, Wolf, Kathrin, additional, Zhang, Siqi, additional, Wang-Sattler, Rui, additional, Prehn, Cornelia, additional, Adamski, Jerzy, additional, Peters, Annette, additional, and Breitner, Susanne, additional

Published
2023
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25. A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene

Author

Jensen, Lars R., Garrett, Lillian, Hölter, Sabine M., Rathkolb, Birgit, Rácz, Ildikó, Adler, Thure, Prehn, Cornelia, Hans, Wolfgang, Rozman, Jan, Becker, Lore, Aguilar-Pimentel, Juan Antonio, Puk, Oliver, Moreth, Kristin, Dopatka, Monika, Walther, Diego J., von Bohlen und Halbach, Viola, Rath, Matthias, Delatycki, Martin, Bert, Bettina, Fink, Heidrun, Blümlein, Katharina, Ralser, Markus, Van Dijck, Anke, Kooy, Frank, Stark, Zornitza, Müller, Sabine, Scherthan, Harry, Gecz, Jozef, Wurst, Wolfgang, Wolf, Eckhard, Zimmer, Andreas, Klingenspor, Martin, Graw, Jochen, Klopstock, Thomas, Busch, Dirk, Adamski, Jerzy, Fuchs, Helmut, Gailus-Durner, Valérie, de Angelis, Martin Hrabě, von Bohlen und Halbach, Oliver, Ropers, Hans-Hilger, and Kuss, Andreas W.

Published
2019
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26. Multi-omics insights into functional alterations of the liver in insulin-deficient diabetes mellitus

Author

Backman, Mattias, Flenkenthaler, Florian, Blutke, Andreas, Dahlhoff, Maik, Ländström, Erik, Renner, Simone, Philippou-Massier, Julia, Krebs, Stefan, Rathkolb, Birgit, Prehn, Cornelia, Grzybek, Michal, Coskun, Ünal, Rothe, Michael, Adamski, Jerzy, de Angelis, Martin Hrabĕ, Wanke, Rüdiger, Fröhlich, Thomas, Arnold, Georg J., Blum, Helmut, and Wolf, Eckhard

Published
2019
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27. Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study

Author

Cai, Xinting, primary, Thorand, Barbara, additional, Hohenester, Simon, additional, Prehn, Cornelia, additional, Cecil, Alexander, additional, Adamski, Jerzy, additional, Zeller, Tanja, additional, Dennis, Andrea, additional, Banerjee, Rajarshi, additional, Peters, Annette, additional, Yaghootkar, Hanieh, additional, and Nano, Jana, additional

Published
2023
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28. Missing view completion for multi-timepoints omics data via representation disentanglement and temporal knowledge transfer

Author

Han, Siyu, primary, Yu, Shixiang, additional, Shi, Mengya, additional, Harada, Makoto, additional, Ge, Jianhong, additional, Lin, Jiesheng, additional, Prehn, Cornelia, additional, Petrera, Agnese, additional, Li, Ying, additional, Sam, Flora, additional, Matullo, Giuseppe, additional, Adamski, Jerzy, additional, Suhre, Karsten, additional, Gieger, Christian, additional, Hauck, Stefanie M., additional, Herder, Christian, additional, Roden, Michael, additional, Casale, Francesco Paolo, additional, Cai, Na, additional, Peters, Annette, additional, and Wang-Sattler, Rui, additional

Published
2023
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29. Circulating metabolites improve the prediction of renal impairment in patients with type 2 diabetes

Author

Trischitta, Vincenzo, primary, Mastroianno, Mario, additional, Scarale, Maria Giovanna, additional, Prehn, Cornelia, additional, Salvemini, Lucia, additional, Fontana, Andrea, additional, Adamski, Jerzy, additional, Schena, Francesco Paolo, additional, Cosmo, Salvatore De, additional, Copetti, Massimiliano, additional, and Menzaghi, Claudia, additional

Published
2023
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30. The HuMet Repository: Watching human metabolism at work

Author

Weinisch, Patrick, primary, Raffler, Johannes, additional, Römisch-Margl, Werner, additional, Arnold, Matthias, additional, Mohney, Robert P., additional, Rist, Manuela J., additional, Prehn, Cornelia, additional, Skurk, Thomas, additional, Hauner, Hans, additional, Daniel, Hannelore, additional, Suhre, Karsten, additional, and Kastenmüller, Gabi, additional

Published
2023
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31. Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice

Author

Xie, Kan, Ryan, Devon P., Pearson, Brandon L., Henzel, Kristin S., Neff, Frauke, Vidal, Ramon O., Hennion, Magali, Lehmann, Isabelle, Schleif, Melvin, Schröder, Susanne, Adler, Thure, Rathkolb, Birgit, Rozman, Jan, Schütz, Anna-Lena, Prehn, Cornelia, Mickael, Michel E., Weiergräber, Marco, Adamski, Jerzy, Busch, Dirk H., Ehninger, Gerhard, Matynia, Anna, Jackson, Walker S., Wolf, Eckhard, Fuchs, Helmut, Gailus-Durner, Valerie, Bonn, Stefan, de Angelis, Martin Hrabě, and Ehninger, Dan

Published
2018

33. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren

Published
2020
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34. Identification of candidate metabolite biomarkers for metabolic syndrome and its five components in population-based human cohorts

Author

Shi, Mengya, primary, Han, Siyu, additional, Klier, Kristin, additional, Fobo, Gisela, additional, Montrone, Corinna, additional, Yu, Shixiang, additional, Harada, Makoto, additional, Henning, Ann-Kristin, additional, Friedrich, Nele, additional, Bahls, Martin, additional, Dörr, Marcus, additional, Nauck, Matthias, additional, Völzke, Henry, additional, Homuth, Georg, additional, Grabe, Hans J., additional, Prehn, Cornelia, additional, Adamski, Jerzy, additional, Suhre, Karsten, additional, Rathmann, Wolfgang, additional, Ruepp, Andreas, additional, Hertel, Johannes, additional, Peters, Annette, additional, and Wang-Sattler, Rui, additional

Published
2023
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36. Association of Atopic Dermatitis with Cardiovascular Risk Factors and Diseases

Author

Standl, Marie, Tesch, Falko, Baurecht, Hansjörg, Rodríguez, Elke, Müller-Nurasyid, Martina, Gieger, Christian, Peters, Annette, Wang-Sattler, Rui, Prehn, Cornelia, Adamski, Jerzy, Kronenberg, Florian, Schulz, Holger, Koletzko, Sibylle, Schikowski, Tamara, von Berg, Andrea, Lehmann, Irina, Berdel, Dietrich, Heinrich, Joachim, Schmitt, Jochen, and Weidinger, Stephan

Published
2017
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38. The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium

Author

Guida, Florence, Tan, Vanessa Y., Corbin, Laura J., Smith-Byrne, Karl, Alcala, Karine, Langenberg, Claudia, Stewart, Isobel D., Butterworth, Adam S., Surendran, Praveen, Achaintre, David, Adamski, Jerzy, Amiano Exezarreta, Pilar, Bergmann, Manuela M., Bull, Caroline J., Dahm, Christina C., Gicquiau, Audrey, Giles, Graham G., Gunter, Marc J., Haller, Toomas, Langhammer, Arnulf, Larose, Tricia L., Ljungberg, Börje, Metspalu, Andres, Milne, Roger L., Muller, David C., Nøst, Therese H., Pettersen Sørgjerd, Elin, Prehn, Cornelia, Riboli, Elio, Rinaldi, Sabina, Rothwell, Joseph A., Scalbert, Augustin, Schmidt, Julie A., Severi, Gianluca, Sieri, Sabina, Vermeulen, Roel, Vincent, Emma E., Waldenberger, Melanie, Timpson, Nicholas J., and Johansson, Mattias

Subjects
Kidney cancer -- Risk factors -- Development and progression -- Physiological aspects, Metabolites -- Health aspects -- Measurement, Body mass index, Biological sciences
Abstract

Background Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). Methods and findings We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 x 10.sup.-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 x 10.sup.-5 ), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ß.sub.BMI ] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 x 10.sup.-5). BMI was also associated with increased levels of glutamate (ß.sub.BMI : 0.12, p = 1.5 x 10.sup.-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds. Conclusions This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer., Author(s): Florence Guida 1, Vanessa Y. Tan 2,3, Laura J. Corbin 2,3, Karl Smith-Byrne 1, Karine Alcala 1, Claudia Langenberg 4, Isobel D. Stewart 4, Adam S. Butterworth 5,6,7,8, Praveen [...]

Published
2021
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40. Fgf9Y162C Mutation Alters Information Processing and Social Memory in Mice

Author

Garrett, Lillian, Becker, Lore, Rozman, Jan, Puk, Oliver, Stoeger, Tobias, Yildirim, Ali Önder, Bohla, Alexander, Eickelberg, Oliver, Hans, Wolfgang, Prehn, Cornelia, Adamski, Jerzy, Klopstock, Thomas, Rácz, Ildikó, Zimmer, Andreas, Klingenspor, Martin, Fuchs, Helmut, Gailus-Durner, Valerie, Wurst, Wolfgang, Hrabě de Angelis, Martin, Graw, Jochen, and Hölter, Sabine M.

Published
2018
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41. Supplementary Figure 1 from Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo

Author

Mycielska, Maria E., primary, Dettmer, Katja, primary, Rümmele, Petra, primary, Schmidt, Katharina, primary, Prehn, Cornelia, primary, Milenkovic, Vladimir M., primary, Jagla, Wolfgang, primary, Madej, Gregor M., primary, Lantow, Margareta, primary, Schladt, Moritz, primary, Cecil, Alexander, primary, Koehl, Gudrun E., primary, Eggenhofer, Elke, primary, Wachsmuth, Christian J., primary, Ganapathy, Vadivel, primary, Schlitt, Hans J., primary, Kunzelmann, Karl, primary, Ziegler, Christine, primary, Wetzel, Christian H., primary, Gaumann, Andreas, primary, Lang, Sven A., primary, Adamski, Jerzy, primary, Oefner, Peter J., primary, and Geissler, Edward K., primary

Published
2023
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42. Data from Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo

Author

Mycielska, Maria E., primary, Dettmer, Katja, primary, Rümmele, Petra, primary, Schmidt, Katharina, primary, Prehn, Cornelia, primary, Milenkovic, Vladimir M., primary, Jagla, Wolfgang, primary, Madej, Gregor M., primary, Lantow, Margareta, primary, Schladt, Moritz, primary, Cecil, Alexander, primary, Koehl, Gudrun E., primary, Eggenhofer, Elke, primary, Wachsmuth, Christian J., primary, Ganapathy, Vadivel, primary, Schlitt, Hans J., primary, Kunzelmann, Karl, primary, Ziegler, Christine, primary, Wetzel, Christian H., primary, Gaumann, Andreas, primary, Lang, Sven A., primary, Adamski, Jerzy, primary, Oefner, Peter J., primary, and Geissler, Edward K., primary

Published
2023
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43. Supplementary Figure S6 from Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo

Author

Mycielska, Maria E., primary, Dettmer, Katja, primary, Rümmele, Petra, primary, Schmidt, Katharina, primary, Prehn, Cornelia, primary, Milenkovic, Vladimir M., primary, Jagla, Wolfgang, primary, Madej, Gregor M., primary, Lantow, Margareta, primary, Schladt, Moritz, primary, Cecil, Alexander, primary, Koehl, Gudrun E., primary, Eggenhofer, Elke, primary, Wachsmuth, Christian J., primary, Ganapathy, Vadivel, primary, Schlitt, Hans J., primary, Kunzelmann, Karl, primary, Ziegler, Christine, primary, Wetzel, Christian H., primary, Gaumann, Andreas, primary, Lang, Sven A., primary, Adamski, Jerzy, primary, Oefner, Peter J., primary, and Geissler, Edward K., primary

Published
2023
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44. Supplementary Table S1 from Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo

Author

Mycielska, Maria E., primary, Dettmer, Katja, primary, Rümmele, Petra, primary, Schmidt, Katharina, primary, Prehn, Cornelia, primary, Milenkovic, Vladimir M., primary, Jagla, Wolfgang, primary, Madej, Gregor M., primary, Lantow, Margareta, primary, Schladt, Moritz, primary, Cecil, Alexander, primary, Koehl, Gudrun E., primary, Eggenhofer, Elke, primary, Wachsmuth, Christian J., primary, Ganapathy, Vadivel, primary, Schlitt, Hans J., primary, Kunzelmann, Karl, primary, Ziegler, Christine, primary, Wetzel, Christian H., primary, Gaumann, Andreas, primary, Lang, Sven A., primary, Adamski, Jerzy, primary, Oefner, Peter J., primary, and Geissler, Edward K., primary

Published
2023
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47. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Author

Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J.M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adragni, Kofi, Allesøe, Rosa Lundbye L., Artati, Anna A., Arumugam, Manimozhiyan, Atabaki-Pasdar, Naeimeh, Baltauss, Tania, Banasik, Karina, Barnett, Anna L., Baum, Patrick, Bell, Jimmy D., Beulens, Joline W., Bianzano, Susanna B., Bizzotto, Roberto, Bonnefond, Amelie, Cabrelli, Louise, Dale, Matilda, Dawed, Adem Y., de Preville, Nathalie, Dekkers, Koen F., Deshmukh, Harshal A., Dings, Christiane, Donnelly, Louise, Dutta, Avirup, Ehrhardt, Beate, Engelbrechtsen, Line, Eriksen, Rebeca, Fan, Yong, Ferrer, Jorge, Fitipaldi, Hugo, Forman, Annemette, Fritsche, Andreas, Froguel, Philippe, Gassenhuber, Johann, Gough, Stephen, Graefe-Mody, Ulrike, Grempler, Rolf, Groeneveld, Lenka, Groop, Leif, Gudmundsdóttir, Valborg, Gupta, Ramneek, Hennige, Anita M.H., Hill, Anita V., Holl, Reinhard W., Hudson, Michelle, Jacobsen, Ulrik Plesner, Jennison, Christopher, Johansen, Joachim, Jonsson, Anna, Karaderi, Tugce, Kaye, Jane, Kennedy, Gwen, Klintenberg, Maria, Kuulasmaa, Teemu, Lehr, Thorsten, Loftus, Heather, Lundgaard, Agnete Troen T., Mazzoni, Gianluca, McRobert, Nicky, McVittie, Ian, Nice, Rachel, Nicolay, Claudia, Nijpels, Giel, Palmer, Colin N., Pedersen, Helle K., Perry, Mandy H., Pomares-Millan, Hugo, Prehn, Cornelia P., Ramisch, Anna, Rasmussen, Simon, Robertson, Neil, Rodriquez, Marianne, Sackett, Peter, Scherer, Nina, Shah, Nisha, Sihinevich, Iryna, Slieker, Roderick C., Sondertoft, Nadja B., Steckel-Hamann, Birgit, Thomas, Melissa K., Thomas, Cecilia Engel E., Thomas, Elizabeth Louise L., Thorand, Barbara, Thorne, Claire E., Tillner, Joachim, Tura, Andrea, Uhlen, Mathias, van Leeuwen, Nienke, van Oort, Sabine, Verkindt, Helene, Vogt, Josef, Wad Sackett, Peter W., Wesolowska-Andersen, Agata, Whitcher, Brandon, White, Margaret W., Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., Viñuela, Ana, Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J.M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adragni, Kofi, Allesøe, Rosa Lundbye L., Artati, Anna A., Arumugam, Manimozhiyan, Atabaki-Pasdar, Naeimeh, Baltauss, Tania, Banasik, Karina, Barnett, Anna L., Baum, Patrick, Bell, Jimmy D., Beulens, Joline W., Bianzano, Susanna B., Bizzotto, Roberto, Bonnefond, Amelie, Cabrelli, Louise, Dale, Matilda, Dawed, Adem Y., de Preville, Nathalie, Dekkers, Koen F., Deshmukh, Harshal A., Dings, Christiane, Donnelly, Louise, Dutta, Avirup, Ehrhardt, Beate, Engelbrechtsen, Line, Eriksen, Rebeca, Fan, Yong, Ferrer, Jorge, Fitipaldi, Hugo, Forman, Annemette, Fritsche, Andreas, Froguel, Philippe, Gassenhuber, Johann, Gough, Stephen, Graefe-Mody, Ulrike, Grempler, Rolf, Groeneveld, Lenka, Groop, Leif, Gudmundsdóttir, Valborg, Gupta, Ramneek, Hennige, Anita M.H., Hill, Anita V., Holl, Reinhard W., Hudson, Michelle, Jacobsen, Ulrik Plesner, Jennison, Christopher, Johansen, Joachim, Jonsson, Anna, Karaderi, Tugce, Kaye, Jane, Kennedy, Gwen, Klintenberg, Maria, Kuulasmaa, Teemu, Lehr, Thorsten, Loftus, Heather, Lundgaard, Agnete Troen T., Mazzoni, Gianluca, McRobert, Nicky, McVittie, Ian, Nice, Rachel, Nicolay, Claudia, Nijpels, Giel, Palmer, Colin N., Pedersen, Helle K., Perry, Mandy H., Pomares-Millan, Hugo, Prehn, Cornelia P., Ramisch, Anna, Rasmussen, Simon, Robertson, Neil, Rodriquez, Marianne, Sackett, Peter, Scherer, Nina, Shah, Nisha, Sihinevich, Iryna, Slieker, Roderick C., Sondertoft, Nadja B., Steckel-Hamann, Birgit, Thomas, Melissa K., Thomas, Cecilia Engel E., Thomas, Elizabeth Louise L., Thorand, Barbara, Thorne, Claire E., Tillner, Joachim, Tura, Andrea, Uhlen, Mathias, van Leeuwen, Nienke, van Oort, Sabine, Verkindt, Helene, Vogt, Josef, Wad Sackett, Peter W., Wesolowska-Andersen, Agata, Whitcher, Brandon, White, Margaret W., Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., and Viñuela, Ana

Abstract

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.

Published
2023

48. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts

Author

Epi Kanker Team B, Cancer, MS MDL 1, Rothwell, Joseph A, Bešević, Jelena, Dimou, Niki, Breeur, Marie, Murphy, Neil, Jenab, Mazda, Wedekind, Roland, Viallon, Vivian, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Scalbert, Augustin, Huybrechts, Inge, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J, Keun, Hector, Chadeau-Hyam, Marc, Boutron-Ruault, Marie-Christine, Overvad, Kim, Dahm, Christina C, Nøst, Therese Haugdahl, Sandanger, Torkjel M, Skeie, Guri, Zamora-Ros, Raul, Tsilidis, Kostas K, Eichelmann, Fabian, Schulze, Matthias B, van Guelpen, Bethany, Vidman, Linda, Sánchez, Maria-José, Amiano, Pilar, Ardanaz, Eva, Smith-Byrne, Karl, Travis, Ruth, Katzke, Verena, Kaaks, Rudolf, Derksen, Jeroen W G, Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Palli, Domenico, Pasanisi, Fabrizio, Eriksen, Anne Kirstine, Tjønneland, Anne, Severi, Gianluca, Gunter, Marc J, Epi Kanker Team B, Cancer, MS MDL 1, Rothwell, Joseph A, Bešević, Jelena, Dimou, Niki, Breeur, Marie, Murphy, Neil, Jenab, Mazda, Wedekind, Roland, Viallon, Vivian, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Scalbert, Augustin, Huybrechts, Inge, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J, Keun, Hector, Chadeau-Hyam, Marc, Boutron-Ruault, Marie-Christine, Overvad, Kim, Dahm, Christina C, Nøst, Therese Haugdahl, Sandanger, Torkjel M, Skeie, Guri, Zamora-Ros, Raul, Tsilidis, Kostas K, Eichelmann, Fabian, Schulze, Matthias B, van Guelpen, Bethany, Vidman, Linda, Sánchez, Maria-José, Amiano, Pilar, Ardanaz, Eva, Smith-Byrne, Karl, Travis, Ruth, Katzke, Verena, Kaaks, Rudolf, Derksen, Jeroen W G, Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Palli, Domenico, Pasanisi, Fabrizio, Eriksen, Anne Kirstine, Tjønneland, Anne, Severi, Gianluca, and Gunter, Marc J

Published
2023

50. Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Author

Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., de Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, Brunak, S. ren, Froguel, Philippe, Thomas, Cecilia Engel, Haussler, Ragna, Beulens, Joline, Rutters, Femke, Nijpels, Giel, van Oort, Sabine, Groeneveld, Lenka, Elders, Petra, Giorgino, Toni, Rodriquez, Marianne, Nice, Rachel, Perry, Mandy, Bianzano, Susanna, Graefe-Mody, Ulrike, Hennige, Anita, Grempler, Rolf, Baum, Patrick, Stærfeldt, Hans-Henrik, Shah, Nisha, Teare, Harriet, Ehrhardt, Beate, Tillner, Joachim, Dings, Christiane, Lehr, Thorsten, Scherer, Nina, Sihinevich, Iryna, Cabrelli, Louise, Loftus, Heather, Bizzotto, Roberto, Tura, Andrea, Dekkers, Koen, van Leeuwen, Nienke, Groop, Leif, Slieker, Roderick, Ramisch, Anna, Jennison, Christopher, McVittie, Ian, Frau, Francesca, Steckel-Hamann, Birgit, Adragni, Kofi, Thomas, Melissa, Pasdar, Naeimeh Atabaki, Fitipaldi, Hugo, Kurbasic, Azra, Mutie, Pascal, Pomares-Millan, Hugo, Bonnefond, Amelie, Canouil, Mickael, Caiazzo, Robert, Verkindt, Helene, Holl, Reinhard, Kuulasmaa, Teemu, Deshmukh, Harshal, Cederberg, Henna, Laakso, Markku, Vangipurapu, Jagadish, Dale, Matilda, Thorand, Barbara, Nicolay, Claudia, Fritsche, Andreas, Hill, Anita, Hudson, Michelle, Thorne, Claire, Allin, Kristine, Arumugam, Manimozhiyan, Jonsson, Anna, Engelbrechtsen, Line, Forman, Annemette, Dutta, Avirup, Sondertoft, Nadja, Fan, Yong, Gough, Stephen, Robertson, Neil, McRobert, Nicky, Wesolowska-Andersen, Agata, Brown, Andrew, Davtian, David, Dawed, Adem, Donnelly, Louise, Palmer, Colin, White, Margaret, Ferrer, Jorge, Whitcher, Brandon, Artati, Anna, Prehn, Cornelia, Adam, Jonathan, Grallert, Harald, Gupta, Ramneek, Sackett, Peter Wad, Nilsson, Birgitte, Tsirigos, Konstantinos, Eriksen, Rebeca, Jablonka, Bernd, Uhlen, Mathias, Gassenhuber, Johann, Baltauss, Tania, de Preville, Nathalie, Klintenberg, Maria, Abdalla, Moustafa, Lundgaard, Agnete Troen [0000-0001-7447-6560], Hernández Medina, Ricardo [0000-0001-6373-2362], Johansen, Joachim [0000-0001-7052-1870], Niu, Lili [0000-0003-4571-4368], Biel, Jorge Hernansanz [0000-0002-3125-2951], Benros, Michael Eriksen [0000-0003-4939-9465], Pedersen, Anders Gorm [0000-0001-9650-8965], Jacobsen, Ulrik Plesner [0000-0001-9181-6854], Koivula, Robert [0000-0002-1646-4163], Vinuela, Ana [0000-0003-3771-8537], Haid, Mark [0000-0001-6118-1333], Hong, Mun-Gwan [0000-0001-8603-8293], Kennedy, Gwen [0000-0002-9856-3236], Thomas, E Louise [0000-0003-4235-4694], Frost, Gary [0000-0003-0529-6325], Hansen, Tue Haldor [0000-0001-5948-8993], Kaye, Jane [0000-0002-7311-4725], Hattersley, Andrew [0000-0001-5620-473X], Ridderstråle, Martin [0000-0002-3270-9167], Pedersen, Oluf [0000-0002-3321-3972], Hansen, Torben [0000-0001-8748-3831], Schwenk, Jochen M [0000-0001-8141-8449], Rasmussen, Simon [0000-0001-6323-9041], Brunak, Søren [0000-0003-0316-5866], Apollo - University of Cambridge Repository, Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, General practice, ACS - Heart failure & arrhythmias, APH - Aging & Later Life, Graduate School, and APH - Methodology

Subjects
Biomedical Engineering, Type 2 diabetes, Bioengineering, Applied Microbiology and Biotechnology, Deep Learning, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Type 2, Machine learning, Molecular Medicine, Humans, Data integration, IMI DIRECT Consortium, Systems biology, Algorithms, Biotechnology
Abstract

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.

Published
2023

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