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51. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

Author: University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Quantitative Genetics, Huffman, Jennifer E., Albrecht, Eva, Teumer, Alexander, Mangino, Massimo, Kapur, Karen, Johnson, Toby, Kutalik, Zoltn, Pirastu, Nicola, Pistis, Giorgio, Lopez, Lorna M., Haller, Toomas, Salo, Perttu, Goel, Anuj, Li, Man, Tanaka, Toshiko, Dehghan, Abbas, Ruggiero, Daniela, Malerba, Giovanni, Smith, Albert V., Nolte, Ilja M., Portas, Laura, Phipps-Green, Amanda, Boteva, Lora, Navarro, Pau, Johansson, Asa, Hicks, Andrew A., Polasek, Ozren, Esko, Tonu, Peden, John F., Harris, Sarah E., Murgia, Federico, Wild, Sarah H., Tenesa, Albert, Tin, Adrienne, Mihailov, Evelin, Grotevendt, Anne, Gislason, Gauti K., Coresh, Josef, D'Adamo, Pio, Ulivi, Sheila, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Kolcic, Ivana, Fisher, Krista, Viigimaa, Margus, Metter, Jeffrey E., Masciullo, Corrado, Trabetti, Elisabetta, Bombieri, Cristina, Sorice, Rossella, Doering, Angela, Reischl, Eva, Strauch, Konstantin, Hofman, Albert, Uitterlinden, Andre G., Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Dalbeth, Nicola, Stamp, Lisa, Smit, Johannes H., Kirin, Mirna, Nagaraja, Ramaiah, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Farrington, Susan M., Theodoratou, Evropi, Jula, Antti, Salomaa, Veikko, Sala, Cinzia, Hengstenberg, Christian, Burnier, Michel, Maegi, Reedik, Klopp, Norman, Kloiber, Stefan, Schipf, Sabine, Ripatti, Samuli, Cabras, Stefano, Soranzo, Nicole, Homuth, Georg, Nutile, Teresa, Munroe, Patricia B., Hastie, Nicholas, Campbell, Harry, Rudan, Igor, Cabrera, Claudia, Haley, Chris, Franco, Oscar H., Merriman, Tony R., Gudnason, Vilmundur, Pirastu, Mario, Penninx, Brenda W., Snieder, Harold, Metspalu, Andres, Ciullo, Marina, Pramstaller, Peter P., van Duijn, Cornelia M., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Dunlop, Malcolm G., Wilson, James F., Gasparini, Paolo, Gyllensten, Ulf, Spector, Tim D., Wright, Alan F., Hayward, Caroline, Watkins, Hugh, Perola, Markus, Bochud, Murielle, Kao, W. H. Linda, Caulfield, Mark, Toniolo, Daniela, Voelzke, Henry, Gieger, Christian, Koettgen, Anna, Vitart, Veronique, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Quantitative Genetics, Huffman, Jennifer E., Albrecht, Eva, Teumer, Alexander, Mangino, Massimo, Kapur, Karen, Johnson, Toby, Kutalik, Zoltn, Pirastu, Nicola, Pistis, Giorgio, Lopez, Lorna M., Haller, Toomas, Salo, Perttu, Goel, Anuj, Li, Man, Tanaka, Toshiko, Dehghan, Abbas, Ruggiero, Daniela, Malerba, Giovanni, Smith, Albert V., Nolte, Ilja M., Portas, Laura, Phipps-Green, Amanda, Boteva, Lora, Navarro, Pau, Johansson, Asa, Hicks, Andrew A., Polasek, Ozren, Esko, Tonu, Peden, John F., Harris, Sarah E., Murgia, Federico, Wild, Sarah H., Tenesa, Albert, Tin, Adrienne, Mihailov, Evelin, Grotevendt, Anne, Gislason, Gauti K., Coresh, Josef, D'Adamo, Pio, Ulivi, Sheila, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Kolcic, Ivana, Fisher, Krista, Viigimaa, Margus, Metter, Jeffrey E., Masciullo, Corrado, Trabetti, Elisabetta, Bombieri, Cristina, Sorice, Rossella, Doering, Angela, Reischl, Eva, Strauch, Konstantin, Hofman, Albert, Uitterlinden, Andre G., Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Dalbeth, Nicola, Stamp, Lisa, Smit, Johannes H., Kirin, Mirna, Nagaraja, Ramaiah, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Farrington, Susan M., Theodoratou, Evropi, Jula, Antti, Salomaa, Veikko, Sala, Cinzia, Hengstenberg, Christian, Burnier, Michel, Maegi, Reedik, Klopp, Norman, Kloiber, Stefan, Schipf, Sabine, Ripatti, Samuli, Cabras, Stefano, Soranzo, Nicole, Homuth, Georg, Nutile, Teresa, Munroe, Patricia B., Hastie, Nicholas, Campbell, Harry, Rudan, Igor, Cabrera, Claudia, Haley, Chris, Franco, Oscar H., Merriman, Tony R., Gudnason, Vilmundur, Pirastu, Mario, Penninx, Brenda W., Snieder, Harold, Metspalu, Andres, Ciullo, Marina, Pramstaller, Peter P., van Duijn, Cornelia M., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Dunlop, Malcolm G., Wilson, James F., Gasparini, Paolo, Gyllensten, Ulf, Spector, Tim D., Wright, Alan F., Hayward, Caroline, Watkins, Hugh, Perola, Markus, Bochud, Murielle, Kao, W. H. Linda, Caulfield, Mark, Toniolo, Daniela, Voelzke, Henry, Gieger, Christian, Koettgen, Anna, and Vitart, Veronique
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
Published: 2015

52. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Author: de Vries, Paul S., Chasman, Daniel I., Sabater-Lleal, Maria, Chen, Ming-Huei, Huffman, Jennifer E., Steri, Maristella, Tang, Weihong, Teumer, Alexander, Marioni, Riccardo E., Grossmann, Vera, Hottenga, Jouke J., Trompet, Stella, Müller-Nurasyid, Martina, Zhao, Jing Hua, Brody, Jennifer A., Kleber, Marcus E., Guo, Xiuqing, Wang, Jie Jin, Auer, Paul L., Attia, John R., Yanek, Lisa R., Ahluwalia, Tarunveer S., Lahti, Jari, Venturini, Cristina, Tanaka, Toshiko, Bielak, Lawrence F., Joshi, Peter K., Rocanin-Arjo, Ares, Kolcic, Ivana, Navarro, Pau, Rose, Lynda M., Oldmeadow, Christopher, Riess, Helene, Mazur, Johanna, Basu, Saonli, Goel, Anuj, Yang, Qiong, Ghanbari, Mohsen, Willemsen, Gonneke, Rumley, Ann, Fiorillo, Edoardo, de Craen, Anton J. M., Grotevendt, Anne, Scott, Robert, Taylor, Kent D., Delgado, Graciela E., Yao, Jie, Kifley, Annette, Kooperberg, Charles, Qayyum, Rehan, Lopez, Lorna M., Berentzen, Tina L., Räikkönen, Katri, Mangino, Massimo, Bandinelli, Stefania, Peyser, Patricia A., Wild, Sarah, Trégouët, David-Alexandre, Wright, Alan F., Marten, Jonathan, Zemunik, Tatijana, Morrison, Alanna C., Sennblad, Bengt, Tofler, Geoffrey, de Maat, Moniek P. M., de Geus, Eco J. C., Lowe, Gordon D., Zoledziewska, Magdalena, Sattar, Naveed, Binder, Harald, Völker, Uwe, Waldenberger, Melanie, Khaw, Kay-Tee, Mcknight, Barbara, Huang, Jie, Jenny, Nancy S., Holliday, Elizabeth G., Qi, Lihong, Mcevoy, Mark G., Becker, Diane M., Starr, John M., Sarin, Antti-Pekka, Hysi, Pirro G., Hernandez, Dena G., Jhun, Min A., Campbell, Harry, Hamsten, Anders, Rivadeneira, Fernando, Mcardle, Wendy L., Slagboom, P. Eline, Zeller, Tanja, Koenig, Wolfgang, Psaty, Bruce M., Haritunians, Talin, Liu, Jingmin, Palotie, Aarno, Uitterlinden, André G., Stott, David J., Hofman, Albert, Franco, Oscar H., Polasek, Ozren, Rudan, Igor, Morange, Pierre-Emmanuel, Wilson, James F., Kardia, Sharon L. R., Ferrucci, Luigi, Spector, Tim D., Eriksson, Johan G., Hansen, Torben, Deary, Ian J., Becker, Lewis C., Scott, Rodney J., Mitchell, Paul, März, Winfried, Wareham, Nick J., Peters, Annette, Greinacher, Andreas, Wild, Philipp S., Jukema, J. Wouter, Boomsma, Dorret I., Hayward, Caroline, Cucca, Francesco, Tracy, Russell, Watkins, Hugh, Reiner, Alex P., Folsom, Aaron R., Ridker, Paul M., O'Donnell, Christopher J., Smith, Nicholas L., Strachan, David P., Dehghan, Abbas, de Vries, Paul S., Chasman, Daniel I., Sabater-Lleal, Maria, Chen, Ming-Huei, Huffman, Jennifer E., Steri, Maristella, Tang, Weihong, Teumer, Alexander, Marioni, Riccardo E., Grossmann, Vera, Hottenga, Jouke J., Trompet, Stella, Müller-Nurasyid, Martina, Zhao, Jing Hua, Brody, Jennifer A., Kleber, Marcus E., Guo, Xiuqing, Wang, Jie Jin, Auer, Paul L., Attia, John R., Yanek, Lisa R., Ahluwalia, Tarunveer S., Lahti, Jari, Venturini, Cristina, Tanaka, Toshiko, Bielak, Lawrence F., Joshi, Peter K., Rocanin-Arjo, Ares, Kolcic, Ivana, Navarro, Pau, Rose, Lynda M., Oldmeadow, Christopher, Riess, Helene, Mazur, Johanna, Basu, Saonli, Goel, Anuj, Yang, Qiong, Ghanbari, Mohsen, Willemsen, Gonneke, Rumley, Ann, Fiorillo, Edoardo, de Craen, Anton J. M., Grotevendt, Anne, Scott, Robert, Taylor, Kent D., Delgado, Graciela E., Yao, Jie, Kifley, Annette, Kooperberg, Charles, Qayyum, Rehan, Lopez, Lorna M., Berentzen, Tina L., Räikkönen, Katri, Mangino, Massimo, Bandinelli, Stefania, Peyser, Patricia A., Wild, Sarah, Trégouët, David-Alexandre, Wright, Alan F., Marten, Jonathan, Zemunik, Tatijana, Morrison, Alanna C., Sennblad, Bengt, Tofler, Geoffrey, de Maat, Moniek P. M., de Geus, Eco J. C., Lowe, Gordon D., Zoledziewska, Magdalena, Sattar, Naveed, Binder, Harald, Völker, Uwe, Waldenberger, Melanie, Khaw, Kay-Tee, Mcknight, Barbara, Huang, Jie, Jenny, Nancy S., Holliday, Elizabeth G., Qi, Lihong, Mcevoy, Mark G., Becker, Diane M., Starr, John M., Sarin, Antti-Pekka, Hysi, Pirro G., Hernandez, Dena G., Jhun, Min A., Campbell, Harry, Hamsten, Anders, Rivadeneira, Fernando, Mcardle, Wendy L., Slagboom, P. Eline, Zeller, Tanja, Koenig, Wolfgang, Psaty, Bruce M., Haritunians, Talin, Liu, Jingmin, Palotie, Aarno, Uitterlinden, André G., Stott, David J., Hofman, Albert, Franco, Oscar H., Polasek, Ozren, Rudan, Igor, Morange, Pierre-Emmanuel, Wilson, James F., Kardia, Sharon L. R., Ferrucci, Luigi, Spector, Tim D., Eriksson, Johan G., Hansen, Torben, Deary, Ian J., Becker, Lewis C., Scott, Rodney J., Mitchell, Paul, März, Winfried, Wareham, Nick J., Peters, Annette, Greinacher, Andreas, Wild, Philipp S., Jukema, J. Wouter, Boomsma, Dorret I., Hayward, Caroline, Cucca, Francesco, Tracy, Russell, Watkins, Hugh, Reiner, Alex P., Folsom, Aaron R., Ridker, Paul M., O'Donnell, Christopher J., Smith, Nicholas L., Strachan, David P., and Dehghan, Abbas
Abstract: Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.
Published: 2015

53. Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population

Author: Anne Grotevendt, Roberto Lorbeer, Sebastian E. Baumeister, Henri Wallaschofski, Henry Völzke, Marcus Dörr, M. Nauck, Ramachandran S. Vasan, and Wolfgang Lieb
Subjects: Male, medicine.medical_specialty, Population, Statistics as Topic, Gastroenterology, Angiopoietin-2, Risk Factors, Internal medicine, Germany, Neoplasms, medicine, Humans, Receptor, education, Cardiovascular mortality, Proportional Hazards Models, education.field_of_study, business.industry, Angiopoietin 2, Hazard ratio, Middle Aged, medicine.disease, Receptor, TIE-2, Confidence interval, Net reclassification improvement, Standardized mortality ratio, Cardiovascular Diseases, Heart failure, Study of Health in Pomerania, Population Surveillance, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Aims To assess the association of circulating concentrations of angiopoietin-2 (Ang-2) and its soluble receptor Tie-2 (sTie-2) with all-cause, cardiovascular, and cancer mortality in a population-based sample. Methods and results Angiopoietin-2 and sTie-2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow-up of 6.2 years, 217 participants died. Ang-2 levels were positively associated with all-cause mortality [HR 1.29; 95% confidence interval (CI) 1.19–1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18–1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89–1.32; P = 0.416). Levels of sTie-2 were not significantly related to all-cause mortality (HR 1.12; 95% CI 0.98–1.27; P = 0.102). Adding Ang-2 to a prediction model for all-cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, −0.015; P = 0.571). Conclusion In our community-based sample, higher serum Ang-2 concentrations were associated with greater risk for all-cause and cardiovascular mortality, suggesting that subtle increases in Ang-2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang-2 to a mortality prediction model only modestly improved discrimination.
Published: 2013

54. Relation of insulin-like growth factor-I and IGF binding protein 3 with markers of inflammation: results of a population-based study

Author: Matthias Nauck, Johannes Lohr, Anne Grotevendt, Henry Völzke, Henri Wallaschofski, and Nele Friedrich
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, Fibrinogen, Logistic regression, Insulin-like growth factor, Endocrinology, Internal medicine, Diabetes mellitus, Medicine, Humans, Insulin-Like Growth Factor I, education, Aged, Inflammation, education.field_of_study, business.industry, Interleukin-6, Odds ratio, Middle Aged, medicine.disease, Confidence interval, C-Reactive Protein, Insulin-Like Growth Factor Binding Protein 3, Study of Health in Pomerania, Female, business, medicine.drug
Abstract: SummaryObjective Previous studies in acromegaly and growth hormone deficiency observed inverse associations between insulin-like growth factor-I (IGF-I) levels and inflammatory biomarkers including high-sensitive C-reactive protein (hsCRP), interleukin-6 or fibrinogen. We aimed to assess the relations between IGF-I or IGF binding protein 3 (IGFBP-3) levels and hsCRP, interleukin-6, fibrinogen and white blood cell count (WBC) in a population-based sample. Design and Patients Data from 3480 subjects from the population-based Study of Health in Pomerania (SHIP) were used. IGF-I, IGFBP-3 and inflammatory biomarkers were measured. Analysis of variance (anova), quantile regression models and logistic regression models, adjusted for age, smoking, diabetes mellitus and waist circumference, were performed. Measurements and Results anova and/or quantile regression showed inverse associations between IGF-I and hsCRP as well as positive associations between IGF-I and fibrinogen among both sexes. Furthermore, the odds of elevated fibrinogen levels increased with increasing IGF-I levels (per SD IGF-I increase: men: odds ratio (OR) 1·35 [95% confidence interval (CI) 1·04, 1·55]; women: OR 1·44 [95% CI 1·21, 1·71]) in both sexes, whereas the odds of increased hsCRP (women: OR 0·46 [95% CI 0·36, 0·58]) and interleukin-6 (men: odds ratio (OR) 0·77 [95% CI 0·61, 0·96]; women: OR 0·69 [95% CI 0·55, 0·86]) decreased. Conclusion Serum IGF-I levels are associated with inflammatory biomarkers including hsCRP, interleukin-6 and fibrinogen. Further experimental studies are needed to elucidate the mechanisms underlying the relation between the GH/IGF axis and the inflammatory system.
Published: 2013

55. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Author: Sabater-Lleal, M., Huang, J., Chasman, D., Naitza, S., Dehghan, A., Johnson, A.D., Teumer, A., Reiner, A.P., Folkersen, L., Basu, S., Rudnicka, A.R., Trompet, S., Malarstig, A., Baumert, J., Bis, J.C., Guo, X.Q., Hottenga, J.J., Shin, S.Y., Lopez, L.M., Lahti, J., Tanaka, T., Yanek, L.R., Oudot-Mellakh, T., Wilson, J.F., Navarro, P., Huffman, J.E., Zemunik, T., Redline, S., Mehra, R., Pulanic, D., Rudan, I., Wright, A.F., Kolcic, I., Polasek, O., Wild, S.H., Campbell, H., Curb, J.D., Wallace, R., Liu, S.M., Eaton, C.B., Becker, D.M., Becker, L.C., Bandinelli, S., Raikkonen, K., Widen, E., Palotie, A., Fornage, M., Green, D., Gross, M., Davies, G., Harris, S.E., Liewald, D.C., Starr, J.M., Williams, F.M.K., Grant, P.J., Spector, T.D., Strawbridge, R.J., Silveira, A., Sennblad, B., Rivadeneira, F., Uitterlinden, A.G., Franco, O.H., Hofman, A., Dongen, J. van, Willemsen, G., Boomsma, D.I., Yao, J., Jenny, N.S., Haritunians, T., McKnight, B., Lumley, T., Taylor, K.D., Rotter, J.I., Psaty, B.M., Peters, A., Gieger, C., Illig, T., Grotevendt, A., Homuth, G., Volzke, H., Kocher, T., Goel, A., Franzosi, M.G., Seedorf, U., Clarke, R., Steri, M., Tarasov, K.V., Sanna, S., Schlessinger, D., Stott, D.J., Sattar, N., Buckley, B.M., Rumley, A., Lowe, G.D., McArdle, W.L., Chen, M.H., Tofler, G.H., Song, J., Boerwinkle, E., Folsom, A.R., Rose, L.M., Franco-Cereceda, A., Teichert, M., Ikram, M.A., Mosley, T.H., Bevan, S., Dichgans, M., Rothwell, P.M., Sudlow, C.L.M., Hopewell, J.C., Chambers, J.C., Saleheen, D., Kooner, J.S., Danesh, J., Nelson, C.P., Erdmann, J., Reilly, M.P., Kathiresan, S., Schunkert, H., Morange, P.E., Ferrucci, L., Eriksson, J.G., Jacobs, D., Deary, I.J., Soranzo, N., Witteman, J.C.M., Geus, E.J.C. de, Tracy, R.P., Hayward, C., Koenig, W., Cucca, F., Jukema, J.W., Eriksson, P., Seshadri, S., Markus, H.S., Watkins, H., Samani, N.J., Wallaschofski, H., Smith, N.L., Tregouet, D., Ridker, P.M., Tang, W.H., Strachan, D.P., Hamsten, A., O'Donnell, C.J., VTE Consortium, STROKE Consortium, WTCCC2, CD4 Consortium, CARDIoGRAM Consortium, Epidemiology, Cell biology, Urology, Internal Medicine, Immunology, Radiology & Nuclear Medicine, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Male, Netherlands Twin Register (NTR), Pathology, Myocardial Infarction, Genome-wide association study, Coronary Artery Disease, Disease, VARIANTS, 030204 cardiovascular system & hematology, Fibrinogen, Genome, 0302 clinical medicine, Risk Factors, Genotype, ARTERY-DISEASE, GENE-EXPRESSION, Aged, 80 and over, Genetics, INDIVIDUAL PARTICIPANT METAANALYSIS, 0303 health sciences, Hispanic or Latino, Venous Thromboembolism, Middle Aged, 3. Good health, Stroke, Meta-analysis, Medical genetics, Female, HEALTH, Cardiology and Cardiovascular Medicine, medicine.drug, Adult, medicine.medical_specialty, cardiovascular diseases, fibrinogen, gene expression, genome-wide association study, Adolescent, Implementation Science [NCEBP 3], Black People, Polymorphism, Single Nucleotide, White People, Young Adult, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Physiology (medical), medicine, Humans, CORONARY-HEART-DISEASE, HEMOSTASIS, Genetic Predisposition to Disease, Aged, 030304 developmental biology, business.industry, Heritability, GENOTYPES, MYOCARDIAL-INFARCTION, Genetic Loci, RISK-FACTORS, business
Abstract: Background— Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion ( Methods and Results— We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant ( P −8 ) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions— We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013

56. Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study

Author: Till Ittermann, Birte Holtfreter, Anne Grotevendt, Thomas Kocher, Stephan B. Felix, Henry Völzke, Christoph Schäper, Ulrich John, Peter Meisel, Anne Obst, Sven Gläser, Marcus Dörr, Stefanie Richter, and Ralf Ewert
Subjects: Pulmonary and Respiratory Medicine, Spirometry, Adult, Lung Diseases, Male, medicine.medical_specialty, Pathology, Sex Factors, Diffusing capacity, Internal medicine, medicine, Humans, Lung volumes, Prospective Studies, Prospective cohort study, Periodontitis, Lung, Aged, Aged, 80 and over, Inflammation, Carbon Monoxide, medicine.diagnostic_test, business.industry, Respiration, Smoking, Age Factors, Fibrinogen, respiratory system, Middle Aged, medicine.disease, respiratory tract diseases, Respiratory Function Tests, Plethysmography, medicine.anatomical_structure, C-Reactive Protein, Cross-Sectional Studies, Clinical attachment loss, Study of Health in Pomerania, Cardiology, Linear Models, Female, business
Abstract: This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p
Published: 2012

57. Short-term changes of the urine metabolome after bariatric surgery

Author: Anne Grotevendt, Matthias Blüher, Tillmann Wolf, Tobias Lohmann, Arne Jungnickel, Matthias Nauck, Kathrin Budde, Nele Friedrich, Miriam Dressler, Henry Völzke, and Henri Wallaschofksi
Subjects: Adult, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Time Factors, Metabolite, Urinary system, Endocrinology, Diabetes and Metabolism, Bariatric Surgery, Urine, Biochemistry, chemistry.chemical_compound, Young Adult, Weight loss, Diabetes mellitus, Genetics, medicine, Metabolome, Humans, Obesity, Molecular Biology, business.industry, Case-control study, Hippuric acid, Middle Aged, medicine.disease, Surgery, Term (time), chemistry, Case-Control Studies, Molecular Medicine, medicine.symptom, business, Biotechnology
Abstract: Bariatric surgery leads to a loss of excess weight and to a remission of diabetes in a majority of patients. In an attempt to explain these underlying mechanisms, a broad range of metabolic alterations have been suggested. We aimed to investigate short-term changes in the urinary metabolome after bariatric surgery. Data for 50 patients who underwent bariatric surgery at the Municipal Hospital of Dresden-Neustadt, Germany, were used. Healthy controls were selected from the Study of Health in Pomerania. Non-fasting, spontaneous urine samples were collected, (1)H NMR spectroscopic analysis was performed, and metabolites were quantified (Chenomx NMR suite). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) models were carried out (pre-operative versus controls, and post-operative versus controls). On the basis of the urine metabolome separations between pre-operative (predictive ability Q2Y=85.6%; total explained variance R2X=58.3%), or post-operative (Q2Y=82.1%; R2X=44.4%) and controls were possible. Metabolites including hippuric acid, 3-hydroxybutyrate, 2-hydroxyisobutyrate, and trigonelline, were altered among patients. In obese patients, 2-hydroxyisobutyrate levels were higher, whereas trigonelline and hippuric acid levels were lower than in controls. The highest levels of 3-hydroxybutyrate were found in post-operative samples, whereas the metabolite was not present in controls, and only at low levels in pre-operative samples. In conclusion, we demonstrated that the urinary metabotype differs between obese patients and healthy controls. The metabolic alterations identified after bariatric procedures increase our knowledge about the metabolic traits associated with weight reduction. Whether urinary metabotypes might be used for early prediction of a successful bariatric procedure should be evaluated in long-term observations.
Published: 2012

58. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Author: de Vries, Paul S., primary, Chasman, Daniel I., additional, Sabater-Lleal, Maria, additional, Chen, Ming-Huei, additional, Huffman, Jennifer E., additional, Steri, Maristella, additional, Tang, Weihong, additional, Teumer, Alexander, additional, Marioni, Riccardo E., additional, Grossmann, Vera, additional, Hottenga, Jouke J., additional, Trompet, Stella, additional, Müller-Nurasyid, Martina, additional, Zhao, Jing Hua, additional, Brody, Jennifer A., additional, Kleber, Marcus E., additional, Guo, Xiuqing, additional, Wang, Jie Jin, additional, Auer, Paul L., additional, Attia, John R., additional, Yanek, Lisa R., additional, Ahluwalia, Tarunveer S., additional, Lahti, Jari, additional, Venturini, Cristina, additional, Tanaka, Toshiko, additional, Bielak, Lawrence F., additional, Joshi, Peter K., additional, Rocanin-Arjo, Ares, additional, Kolcic, Ivana, additional, Navarro, Pau, additional, Rose, Lynda M., additional, Oldmeadow, Christopher, additional, Riess, Helene, additional, Mazur, Johanna, additional, Basu, Saonli, additional, Goel, Anuj, additional, Yang, Qiong, additional, Ghanbari, Mohsen, additional, Willemsen, Gonneke, additional, Rumley, Ann, additional, Fiorillo, Edoardo, additional, de Craen, Anton J. M., additional, Grotevendt, Anne, additional, Scott, Robert, additional, Taylor, Kent D., additional, Delgado, Graciela E., additional, Yao, Jie, additional, Kifley, Annette, additional, Kooperberg, Charles, additional, Qayyum, Rehan, additional, Lopez, Lorna M., additional, Berentzen, Tina L., additional, Räikkönen, Katri, additional, Mangino, Massimo, additional, Bandinelli, Stefania, additional, Peyser, Patricia A., additional, Wild, Sarah, additional, Trégouët, David-Alexandre, additional, Wright, Alan F., additional, Marten, Jonathan, additional, Zemunik, Tatijana, additional, Morrison, Alanna C., additional, Sennblad, Bengt, additional, Tofler, Geoffrey, additional, de Maat, Moniek P. M., additional, de Geus, Eco J. C., additional, Lowe, Gordon D., additional, Zoledziewska, Magdalena, additional, Sattar, Naveed, additional, Binder, Harald, additional, Völker, Uwe, additional, Waldenberger, Melanie, additional, Khaw, Kay-Tee, additional, Mcknight, Barbara, additional, Huang, Jie, additional, Jenny, Nancy S., additional, Holliday, Elizabeth G., additional, Qi, Lihong, additional, Mcevoy, Mark G., additional, Becker, Diane M., additional, Starr, John M., additional, Sarin, Antti-Pekka, additional, Hysi, Pirro G., additional, Hernandez, Dena G., additional, Jhun, Min A., additional, Campbell, Harry, additional, Hamsten, Anders, additional, Rivadeneira, Fernando, additional, Mcardle, Wendy L., additional, Slagboom, P. Eline, additional, Zeller, Tanja, additional, Koenig, Wolfgang, additional, Psaty, Bruce M., additional, Haritunians, Talin, additional, Liu, Jingmin, additional, Palotie, Aarno, additional, Uitterlinden, André G., additional, Stott, David J., additional, Hofman, Albert, additional, Franco, Oscar H., additional, Polasek, Ozren, additional, Rudan, Igor, additional, Morange, Pierre-Emmanuel, additional, Wilson, James F., additional, Kardia, Sharon L. R., additional, Ferrucci, Luigi, additional, Spector, Tim D., additional, Eriksson, Johan G., additional, Hansen, Torben, additional, Deary, Ian J., additional, Becker, Lewis C., additional, Scott, Rodney J., additional, Mitchell, Paul, additional, März, Winfried, additional, Wareham, Nick J., additional, Peters, Annette, additional, Greinacher, Andreas, additional, Wild, Philipp S., additional, Jukema, J. Wouter, additional, Boomsma, Dorret I., additional, Hayward, Caroline, additional, Cucca, Francesco, additional, Tracy, Russell, additional, Watkins, Hugh, additional, Reiner, Alex P., additional, Folsom, Aaron R., additional, Ridker, Paul M., additional, O'Donnell, Christopher J., additional, Smith, Nicholas L., additional, Strachan, David P., additional, and Dehghan, Abbas, additional
Published: 2015
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59. Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample

Author: Lorbeer, R., primary, Baumeister, S.E., additional, Dörr, M., additional, Felix, S.B., additional, Nauck, M., additional, Grotevendt, A., additional, Markus, M.R.P., additional, von Sarnowski, B., additional, Völzke, H., additional, Vasan, R.S., additional, Wallaschofski, H., additional, and Lieb, W., additional
Published: 2015
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60. No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index:Results from Meta-Analyses of 80,607 Subjects

Author: Baumert, J, Huang, J, McKnight, B, Sabater-Lleal, M, Steri, M, Chu, A.Y., Trompet, Stella, Lopez, L.M., Fornage, M, Teumer, A, Tang, WH, Rudnicka, AR, Malarstig, A, Hottenga, JJ (Jouke Jan), Kavousi, Maryam, Lahti, Jari, Tanaka, Toshiko, Hayward, Caroline, Huffman, JE, Morange, PE, Rose, LM, Basu, S, Rumley, A, Stott, DJ, Buckley, BM, de Craen, AJM, Sanna, S, Masala, M, Biffar, R, Homuth, G, Silveira, A, Sennblad, B, Goel, A, Watkins, H, Muller-Nurasyid, M, Ruckerl, R, Taylor, K, Chen, MH, de Geus, EJC, Hofman, Bert, Witteman, Jacqueline C.M., de Maat, Moniek, Palotie, A, Davies, G, Siscovick, DS, Kolcic, I, Wild, SH, Song, J, McArdle, WL, Ford, I, Sattar, N, Schlessinger, D, Grotevendt, A, Franzosi, MG, Illig, T, Waldenberger, M, Lumley, T, Tofler, GH, Willemsen, G, Uitterlinden, André, Rivadeneira, Fernando, Raikkonen, K, Chasman, DI, Folsom, AR, Lowe, GD, Westendorp, RGJ, Slagboom, PE (Eline), Cucca, F, Wallaschofski, H, Strawbridge, RJ, Seedorf, U, Koenig, W, Bis, JC, Mukamal, KJ, van Dongen, Jenny, Widen, E, Franco Duran, OH, Starr, JM, Liu, Kiang, Ferrucci, L, Polasek, O, Wilson, JF, Oudot-Mellakh, T, Campbell, H, Navarro, P, Bandinelli, S, Eriksson, J, Boomsma, DI, Dehghan, Abbas, Clarke, R, Hamsten, A, Boerwinkle, E, Jukema, JW, Naitza, S, Ridker, PM, Volzke, H, Deary, IJ, Reiner, AP, Tregouet, DA, O'Donnell, CJ, Strachan, DP, Peters, A, Smith, NL, Baumert, J, Huang, J, McKnight, B, Sabater-Lleal, M, Steri, M, Chu, A.Y., Trompet, Stella, Lopez, L.M., Fornage, M, Teumer, A, Tang, WH, Rudnicka, AR, Malarstig, A, Hottenga, JJ (Jouke Jan), Kavousi, Maryam, Lahti, Jari, Tanaka, Toshiko, Hayward, Caroline, Huffman, JE, Morange, PE, Rose, LM, Basu, S, Rumley, A, Stott, DJ, Buckley, BM, de Craen, AJM, Sanna, S, Masala, M, Biffar, R, Homuth, G, Silveira, A, Sennblad, B, Goel, A, Watkins, H, Muller-Nurasyid, M, Ruckerl, R, Taylor, K, Chen, MH, de Geus, EJC, Hofman, Bert, Witteman, Jacqueline C.M., de Maat, Moniek, Palotie, A, Davies, G, Siscovick, DS, Kolcic, I, Wild, SH, Song, J, McArdle, WL, Ford, I, Sattar, N, Schlessinger, D, Grotevendt, A, Franzosi, MG, Illig, T, Waldenberger, M, Lumley, T, Tofler, GH, Willemsen, G, Uitterlinden, André, Rivadeneira, Fernando, Raikkonen, K, Chasman, DI, Folsom, AR, Lowe, GD, Westendorp, RGJ, Slagboom, PE (Eline), Cucca, F, Wallaschofski, H, Strawbridge, RJ, Seedorf, U, Koenig, W, Bis, JC, Mukamal, KJ, van Dongen, Jenny, Widen, E, Franco Duran, OH, Starr, JM, Liu, Kiang, Ferrucci, L, Polasek, O, Wilson, JF, Oudot-Mellakh, T, Campbell, H, Navarro, P, Bandinelli, S, Eriksson, J, Boomsma, DI, Dehghan, Abbas, Clarke, R, Hamsten, A, Boerwinkle, E, Jukema, JW, Naitza, S, Ridker, PM, Volzke, H, Deary, IJ, Reiner, AP, Tregouet, DA, O'Donnell, CJ, Strachan, DP, Peters, A, and Smith, NL
Abstract: Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2x10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.
Published: 2014

61. No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects

Author: Baumert, Jens, primary, Huang, Jie, additional, McKnight, Barbara, additional, Sabater-Lleal, Maria, additional, Steri, Maristella, additional, Chu, Audrey Y., additional, Trompet, Stella, additional, Lopez, Lorna M., additional, Fornage, Myriam, additional, Teumer, Alexander, additional, Tang, Weihong, additional, Rudnicka, Alicja R., additional, Mälarstig, Anders, additional, Hottenga, Jouke-Jan, additional, Kavousi, Maryam, additional, Lahti, Jari, additional, Tanaka, Toshiko, additional, Hayward, Caroline, additional, Huffman, Jennifer E., additional, Morange, Pierre-Emmanuel, additional, Rose, Lynda M., additional, Basu, Saonli, additional, Rumley, Ann, additional, Stott, David J., additional, Buckley, Brendan M., additional, de Craen, Anton J. M., additional, Sanna, Serena, additional, Masala, Marco, additional, Biffar, Reiner, additional, Homuth, Georg, additional, Silveira, Angela, additional, Sennblad, Bengt, additional, Goel, Anuj, additional, Watkins, Hugh, additional, Müller-Nurasyid, Martina, additional, Rückerl, Regina, additional, Taylor, Kent, additional, Chen, Ming-Huei, additional, de Geus, Eco J. C., additional, Hofman, Albert, additional, Witteman, Jacqueline C. M., additional, de Maat, Moniek P. M., additional, Palotie, Aarno, additional, Davies, Gail, additional, Siscovick, David S., additional, Kolcic, Ivana, additional, Wild, Sarah H., additional, Song, Jaejoon, additional, McArdle, Wendy L., additional, Ford, Ian, additional, Sattar, Naveed, additional, Schlessinger, David, additional, Grotevendt, Anne, additional, Franzosi, Maria Grazia, additional, Illig, Thomas, additional, Waldenberger, Melanie, additional, Lumley, Thomas, additional, Tofler, Geoffrey H., additional, Willemsen, Gonneke, additional, Uitterlinden, André G., additional, Rivadeneira, Fernando, additional, Räikkönen, Katri, additional, Chasman, Daniel I., additional, Folsom, Aaron R., additional, Lowe, Gordon D., additional, Westendorp, Rudi G. J., additional, Slagboom, P. Eline, additional, Cucca, Francesco, additional, Wallaschofski, Henri, additional, Strawbridge, Rona J., additional, Seedorf, Udo, additional, Koenig, Wolfgang, additional, Bis, Joshua C., additional, Mukamal, Kenneth J., additional, van Dongen, Jenny, additional, Widen, Elisabeth, additional, Franco, Oscar H., additional, Starr, John M., additional, Liu, Kiang, additional, Ferrucci, Luigi, additional, Polasek, Ozren, additional, Wilson, James F., additional, Oudot-Mellakh, Tiphaine, additional, Campbell, Harry, additional, Navarro, Pau, additional, Bandinelli, Stefania, additional, Eriksson, Johan, additional, Boomsma, Dorret I., additional, Dehghan, Abbas, additional, Clarke, Robert, additional, Hamsten, Anders, additional, Boerwinkle, Eric, additional, Jukema, J. Wouter, additional, Naitza, Silvia, additional, Ridker, Paul M., additional, Völzke, Henry, additional, Deary, Ian J., additional, Reiner, Alexander P., additional, Trégouët, David-Alexandre, additional, O'Donnell, Christopher J., additional, Strachan, David P., additional, Peters, Annette, additional, and Smith, Nicholas L., additional
Published: 2014
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62. Efficient and selective telomerization of 1,3-butadiene with diols catalyzed by palladium-carbene complexes

Author: Matthias Beller, Ralf Jackstell, Anne Grotevendt, Dirk Michalik, and Mario Dr. Gomez
Subjects: inorganic chemicals, Polymers, General Chemical Engineering, chemistry.chemical_element, Homogeneous catalysis, Ether, Catalysis, Substrate Specificity, chemistry.chemical_compound, Glycols, Butadienes, Organometallic Compounds, Environmental Chemistry, Organic chemistry, General Materials Science, Group 2 organometallic chemistry, 1,3-Butadiene, General Energy, Telomerization (dimerization), chemistry, Carbene, Methane, Palladium, Ethers
Abstract: The selective telomerization of 1,3-butadiene with seven different linear and cyclic diols proceeds in the presence of in situ generated palladium carbene catalysts. By applying optimized reaction conditions, including very low metal loadings (2-10 ppm), excellent catalyst turnover numbers (>250,000) and good chemoselectivities are observed with respect to the mono-octadienyl ether derivatives. This protocol allows the efficient preparation of unsaturated alcohols, which are useful for various applications.
Published: 2008

63. ChemInform Abstract: Development of Palladium-Carbene Catalysts for Telomerization and Dimerization of 1,3-Dienes: Form Basic Research to Industrial Applications

Author: Ralf Jackstell, Nicolas D. Clement, Lucie Routaboul, Anne Grotevendt, and Matthias Beller
Subjects: chemistry.chemical_compound, Telomerization (dimerization), chemistry, Basic research, chemistry.chemical_element, Organic chemistry, General Medicine, Carbene, Palladium, Catalysis
Published: 2008

64. Development of palladium-carbene catalysts for telomerization and dimerization of 1,3-dienes: from basic research to industrial applications

Author: Nicolas D. Clement, Ralf Jackstell, Anne Grotevendt, Matthias Beller, and Lucie Routaboul
Subjects: Green chemistry, Models, Molecular, Molecular Structure, Organic Chemistry, chemistry.chemical_element, Pilot Projects, General Chemistry, Crystallography, X-Ray, Catalysis, Alkadienes, chemistry.chemical_compound, Pilot plant, Telomerization (dimerization), chemistry, Basic research, Chemical Industry, Organometallic Compounds, Organic chemistry, Hydrogenation, Carbene, Dimerization, Methane, Palladium
Abstract: The following account summarises recent developments in the area of palladium-catalysed telomerisation and dimerisation reactions of 1,3-dienes. The most active types of catalyst, palladium-carbene complexes, were tested in pilot plant and proved to be industrially viable.
Published: 2008

65. Development of a general and efficient iron-catalyzed epoxidation with hydrogen peroxide as oxidant

Author: Ralf Jackstell, Gopinathan Anilkumar, Bianca Bitterlich, Anne Grotevendt, Man Kin Tse, Bjoern Spilker, Feyissa Gadissa Gelalcha, and Matthias Beller
Subjects: Models, Molecular, Iron, Homogeneous catalysis, Systematic variation, Alkenes, Biochemistry, Ferric Compounds, Catalysis, Metal, chemistry.chemical_compound, Stilbenes, Organic chemistry, Industry, Reactivity (chemistry), Ferrous Compounds, Hydrogen peroxide, Reaction conditions, Chemistry, Iron catalyzed, Organic Chemistry, General Medicine, General Chemistry, Hydrogen Peroxide, Oxidants, Combinatorial chemistry, Enzymes, visual_art, visual_art.visual_art_medium, Epoxy Compounds, Selectivity
Abstract: The development of inexpensive and practical iron catalysts for the environmentally benign epoxidation of olefins with hydrogen peroxide as terminal oxidant is described. By systematic variation of ligands, metal sources, and reaction conditions, it was discovered that FeCl3 x 6 H2O in combination with pyridine-2,6-dicarboxylic acid and different amines shows high reactivity and excellent selectivity towards the epoxidation of aromatic olefins and moderate reactivity towards that of aliphatic olefins.
Published: 2007

66. Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample

Author: Marcello Ricardo Paulista Markus, Anne Grotevendt, Matthias Nauck, Henri Wallaschofski, Bettina von Sarnowski, Stephan B. Felix, Sebastian E. Baumeister, Wolfgang Lieb, Roberto Lorbeer, Marcus Dörr, Ramachandran S. Vasan, and Henry Völzke
Subjects: Adult, Male, medicine.medical_specialty, Cross-sectional study, Population, Disease, Rate ratio, Carotid Intima-Media Thickness, Angiopoietin-2, Risk Factors, Germany, medicine.artery, Internal medicine, Humans, Medicine, Common carotid artery, education, Receptor, Survival rate, Aged, Retrospective Studies, Subclinical infection, Aged, 80 and over, education.field_of_study, business.industry, Incidence, Angiopoietin 2, Population based sample, Middle Aged, Receptor, TIE-2, Survival Rate, Cross-Sectional Studies, Endocrinology, Intima-media thickness, Cardiovascular Diseases, Echocardiography, Population Surveillance, Study of Health in Pomerania, Immunology, Disease Progression, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
Abstract: Objective Higher circulating Angiopoietin-2 (Ang-2) levels predict cardiovascular events and mortality in clinical samples and in the general population. To better understand the underlying mechanisms, we investigated the association of circulating Ang-2 and sTie-2 (the soluble form of the Ang-2 receptor) levels with various measures of subclinical cardiovascular disease. Methods Cross-sectional data of 3204 participants (1654 women) aged 25–88 years from the population-based Study of Health in Pomerania were analysed. LV mass (LVM) and fractional shortening were determined echocardiographically as indices of cardiac structure and function, respectively. Intima media thickness (IMT) of the common carotid artery, the number of carotid plaques and flow-mediated dilation (FMD) were used to characterise large and medium-sized arterial structure and function. Results Multivariable-adjusted linear and negative binomial regression models revealed an inverse association of circulating Ang-2 levels (independent variable) with fractional shortening (s=−0.51 per 1 SD increment; 95% CI −0.86 to −0.16, p=0.005) and a positive association with number of carotid plaques (rate ratio=1.04 95% CI 1.01 to 1.07, p=0.019). No associations of Ang-2 or sTie-2 with LVM, IMT and FMD were found. Conclusions Circulating Ang-2 levels were associated with select subclinical cardiovascular disease traits, consistent with the notion that the Ang-2-pathway plays a role in mediating cardiovascular morbidity.
Published: 2015

67. Synthesis of a New Chiral N,N,N-Tridentate Pyridinebisimidazole Ligand Library and Its Application in Ru-Catalyzed Asymmetric Epoxidation

Author: Markus Klawonn, Christian Doebler, Santosh Bhor, Matthias Beller, Anne Grotevendt, Man Kin Tse, Gopinathan Anilkumar, and Bianca Bitterlich
Subjects: Ligand, Stereochemistry, Chemistry, General Medicine, Catalysis
Published: 2005

68. Synthesis of a new chiral N,N,N-tridentate pyridinebisimidazoline ligand library and its application in Ru-catalyzed asymmetric epoxidation

Author: Santosh Bhor, Christian Döbler, Markus Klawonn, Matthias Beller, Bianca Bitterlich, and Anne Grotevendt, Man Kin Tse, and Gopinathan Anilkumar
Subjects: chemistry.chemical_compound, chemistry, Stereochemistry, Ligand, Organic Chemistry, Physical and Theoretical Chemistry, Hydrogen peroxide, Biochemistry, Combinatorial chemistry, Catalysis
Abstract: A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins. [reaction: see text]
Published: 2005

69. Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample

Author: Lorbeer, Roberto, primary, Baumeister, Sebastian E, additional, Dörr, Marcus, additional, Felix, Stephan B, additional, Nauck, Matthias, additional, Grotevendt, Anne, additional, Markus, Marcello R P, additional, von Sarnowski, Bettina, additional, Völzke, Henry, additional, Vasan, Ramachandran S, additional, Wallaschofski, Henri, additional, and Lieb, Wolfgang, additional
Published: 2014
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70. Abdominal obesity modifies long-term associations between periodontitis and markers of systemic inflammation

Author: Gocke, Christiane, primary, Holtfreter, Birte, additional, Meisel, Peter, additional, Grotevendt, Anne, additional, Jablonowski, Lukasz, additional, Nauck, Matthias, additional, Markus, Marcello Ricardo Paulista, additional, and Kocher, Thomas, additional
Published: 2014
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71. Circulating angiopoietin-2, its soluble receptor tie-2 and mortality in the general population

Author: Lorbeer, R., primary, Baumeister, S.E., additional, Dörr, M., additional, Nauck, M., additional, Grotevendt, A., additional, Völzke, H., additional, Vasan, R.S., additional, Wallaschofski, H., additional, and Lieb, W., additional
Published: 2014
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72. Cross-sectional and longitudinal relation of IGF1 and IGF-binding protein 3 with lipid metabolism

Author: Eggert, Marie-Luise, primary, Wallaschofski, Henri, additional, Grotevendt, Anne, additional, Nauck, Matthias, additional, Völzke, Henry, additional, Samietz, Stefanie, additional, and Friedrich, Nele, additional
Published: 2014
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73. Acquired Hemophilia With Inhibitors Presenting as an Emergency

Author: Sümnig, Ariane, primary, Grotevendt, Anne, additional, Westphal, Antje, additional, Fiene, Michael, additional, Greinacher, Andreas, additional, and Thiele, Thomas, additional
Published: 2014
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74. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Author: Koettgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M., Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D., Kutalik, Zoltan, Smith, Albert V., Shi, Julia, Struchalin, Maksim, Middelberg, Rita P. S., Brown, Morris J., Gaffo, Angelo L., Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F., Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E., Hicks, Andrew A., Nolte, Ilja M., Johansson, Åsa, Murgia, Federico, Wild, Sarah H., Bakker, Stephan J. L., Peden, John F., Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M., Lehtimaki, Terho, Woodward, Owen M., Okada, Yukinori, Tin, Adrienne, Mueller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B., Launer, Lenore J., McArdle, Patrick, Shuldiner, Alan R., Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G., Montgomery, Grant W., Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B., Samani, Nilesh J., Jacobs, David R., Jr., Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I., Psaty, Bruce M., Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tonu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J., Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S., Scott, Rodney J., Holliday, Elizabeth G., Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E., Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Doering, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Bruinenberg, Marcel, Stolk, Ronald P., Kooner, Jaspal S., Zhang, Weihua, Winkelmann, Bernhard R., Boehm, Bernhard O., Lucae, Susanne, Penninx, Brenda W., Smit, Johannes H., Curhan, Gary, Mudgal, Poorva, Plenge, Robert M., Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F., Leach, Irene Mateo, van Gilst, Wiek H., Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M., Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D., Sala, Cinzia, Ridker, Paul M., Kaehoenen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P., Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Singleton, Andrew B., Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L., Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M., Voelzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B., Fornage, Myriam, Gasparini, Paolo, Siscovick, David S., Polasek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J. F., van Duijn, Cornelia M., Borecki, Ingrid B., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Wolffenbuttel, Bruce H. R., Chambers, John C., Maerz, Winfried, Pramstaller, Peter P., Snieder, Harold, Gyllensten, Ulf, Wright, Alan F., Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C. M., Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G., Toenjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I., Raitakari, Olli, Kao, W. H. Linda, Ciullo, Marina, Fox, Caroline S., Caulfield, Mark, Bochud, Murielle, Gieger, Christian, Koettgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M., Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D., Kutalik, Zoltan, Smith, Albert V., Shi, Julia, Struchalin, Maksim, Middelberg, Rita P. S., Brown, Morris J., Gaffo, Angelo L., Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F., Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E., Hicks, Andrew A., Nolte, Ilja M., Johansson, Åsa, Murgia, Federico, Wild, Sarah H., Bakker, Stephan J. L., Peden, John F., Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M., Lehtimaki, Terho, Woodward, Owen M., Okada, Yukinori, Tin, Adrienne, Mueller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B., Launer, Lenore J., McArdle, Patrick, Shuldiner, Alan R., Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G., Montgomery, Grant W., Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B., Samani, Nilesh J., Jacobs, David R., Jr., Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I., Psaty, Bruce M., Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tonu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J., Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S., Scott, Rodney J., Holliday, Elizabeth G., Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E., Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Doering, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Bruinenberg, Marcel, Stolk, Ronald P., Kooner, Jaspal S., Zhang, Weihua, Winkelmann, Bernhard R., Boehm, Bernhard O., Lucae, Susanne, Penninx, Brenda W., Smit, Johannes H., Curhan, Gary, Mudgal, Poorva, Plenge, Robert M., Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F., Leach, Irene Mateo, van Gilst, Wiek H., Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M., Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D., Sala, Cinzia, Ridker, Paul M., Kaehoenen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P., Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Singleton, Andrew B., Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L., Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M., Voelzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B., Fornage, Myriam, Gasparini, Paolo, Siscovick, David S., Polasek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J. F., van Duijn, Cornelia M., Borecki, Ingrid B., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Wolffenbuttel, Bruce H. R., Chambers, John C., Maerz, Winfried, Pramstaller, Peter P., Snieder, Harold, Gyllensten, Ulf, Wright, Alan F., Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C. M., Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G., Toenjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I., Raitakari, Olli, Kao, W. H. Linda, Ciullo, Marina, Fox, Caroline S., Caulfield, Mark, Bochud, Murielle, and Gieger, Christian
Abstract: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Published: 2013
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75. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Author: UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M, van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, Gieger, Christian, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M, van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, and Gieger, Christian
Published: 2013

76. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Author: LifeLines Cohort Study, CARDIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium, Köttgen, A., Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, C.M., Haller, T., Yang, Q., Tanaka, T., Johnson, A.D., Kutalik, Z., Smith, A.V., Shi, J., Struchalin, M., Middelberg, R.P., Brown, M.J., Gaffo, A.L., Pirastu, N., Li, G., Hayward, C., Zemunik, T., Huffman, J., Yengo, L., Zhao, J.H., Demirkan, A., Feitosa, M.F., Liu, X., Malerba, G., Lopez, L.M., van der Harst, P., Li, X., Kleber, M.E., Hicks, A.A., Nolte, I.M., Johansson, A., Murgia, F., Wild, S.H., Bakker, S.J., Peden, J.F., Dehghan, A., Steri, M., Tenesa, A., Lagou, V., Salo, P., Mangino, M., Rose, L.M., Lehtimäki, T., Woodward, O.M., Okada, Y., Tin, A., Müller, C., Oldmeadow, C., Putku, M., Czamara, D., Kraft, P., Frogheri, L., Thun, G.A., Grotevendt, A., Gislason, G.K., Harris, T.B., Launer, L.J., McArdle, P., Shuldiner, A.R., Boerwinkle, E., Coresh, J., Schmidt, H., Schallert, M., Martin, N.G., Montgomery, G.W., Kubo, M., Nakamura, Y., Munroe, P.B., Samani, N.J., Jacobs, D.R., Liu, K., D'Adamo, P., Ulivi, S., Rotter, J.I., Psaty, B.M., Vollenweider, P., Waeber, G., Campbell, S., Devuyst, O., Navarro, P., Kolcic, I., Hastie, N., Balkau, B., Froguel, P., Esko, T., Salumets, A., Khaw, K.T., Langenberg, C., Wareham, N.J., Isaacs, A., Kraja, A., Zhang, Q., Wild, P.S., Scott, R.J., Holliday, E.G., Org, E., Viigimaa, M., Bandinelli, S., Metter, J.E., Lupo, A., Trabetti, E., Sorice, R., Döring, A., Lattka, E., Strauch, K., Theis, F., Waldenberger, M., Wichmann, H.E., Davies, G., Gow, A.J., Bruinenberg, M., Stolk, R.P., Kooner, J.S., Zhang, W., Winkelmann, B.R., Boehm, B.O., Lucae, S., Penninx, B.W., Smit, J.H., Curhan, G., Mudgal, P., Plenge, R.M., Portas, L., Persico, I., Kirin, M., Wilson, J.F., Mateo Leach, I., van Gilst, W.H., Goel, A., Ongen, H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Imboden, M., von Eckardstein, A., Cucca, F., Nagaraja, R., Piras, M.G., Nauck, M., Schurmann, C., Budde, K., Ernst, F., Farrington, S.M., Theodoratou, E., Prokopenko, I., Stumvoll, M., Jula, A., Perola, M., Salomaa, V., Shin, S.Y., Spector, T.D., Sala, C., Ridker, P.M., Kähönen, M., Viikari, J., Hengstenberg, C., Nelson, C.P., Meschia, J.F., Nalls, M.A., Sharma, P., Singleton, A.B., Kamatani, N., Zeller, T., Burnier, M., Attia, J., Laan, M., Klopp, N., Hillege, H.L., Kloiber, S., Choi, H., Pirastu, M., Tore, S., Probst-Hensch, N.M., Völzke, H., Gudnason, V., Parsa, A., Schmidt, R., Whitfield, J.B., Fornage, M., Gasparini, P., Siscovick, D.S., Pola?ek O., Campbell, H., Rudan, I., Bouatia-Naji, N., Metspalu, A., Loos, R.J., van Duijn, C.M., Borecki, I.B., Ferrucci, L., Gambaro, G., Deary, I.J., Wolffenbuttel, B.H., Chambers, J.C., März, W., Pramstaller, P.P., Snieder, H., Gyllensten, U., Wright, A.F., Navis, G., Watkins, H., Witteman, J.C., Sanna, S., Schipf, S., Dunlop, M.G., Tönjes, A., Ripatti, S., Soranzo, N., Toniolo, D., Chasman, D.I., Raitakari, O., Kao, W.H., Ciullo, M., Fox, C.S., Caulfield, M., Bochud, M., Gieger, C., LifeLines Cohort Study, CARDIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium, Köttgen, A., Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, C.M., Haller, T., Yang, Q., Tanaka, T., Johnson, A.D., Kutalik, Z., Smith, A.V., Shi, J., Struchalin, M., Middelberg, R.P., Brown, M.J., Gaffo, A.L., Pirastu, N., Li, G., Hayward, C., Zemunik, T., Huffman, J., Yengo, L., Zhao, J.H., Demirkan, A., Feitosa, M.F., Liu, X., Malerba, G., Lopez, L.M., van der Harst, P., Li, X., Kleber, M.E., Hicks, A.A., Nolte, I.M., Johansson, A., Murgia, F., Wild, S.H., Bakker, S.J., Peden, J.F., Dehghan, A., Steri, M., Tenesa, A., Lagou, V., Salo, P., Mangino, M., Rose, L.M., Lehtimäki, T., Woodward, O.M., Okada, Y., Tin, A., Müller, C., Oldmeadow, C., Putku, M., Czamara, D., Kraft, P., Frogheri, L., Thun, G.A., Grotevendt, A., Gislason, G.K., Harris, T.B., Launer, L.J., McArdle, P., Shuldiner, A.R., Boerwinkle, E., Coresh, J., Schmidt, H., Schallert, M., Martin, N.G., Montgomery, G.W., Kubo, M., Nakamura, Y., Munroe, P.B., Samani, N.J., Jacobs, D.R., Liu, K., D'Adamo, P., Ulivi, S., Rotter, J.I., Psaty, B.M., Vollenweider, P., Waeber, G., Campbell, S., Devuyst, O., Navarro, P., Kolcic, I., Hastie, N., Balkau, B., Froguel, P., Esko, T., Salumets, A., Khaw, K.T., Langenberg, C., Wareham, N.J., Isaacs, A., Kraja, A., Zhang, Q., Wild, P.S., Scott, R.J., Holliday, E.G., Org, E., Viigimaa, M., Bandinelli, S., Metter, J.E., Lupo, A., Trabetti, E., Sorice, R., Döring, A., Lattka, E., Strauch, K., Theis, F., Waldenberger, M., Wichmann, H.E., Davies, G., Gow, A.J., Bruinenberg, M., Stolk, R.P., Kooner, J.S., Zhang, W., Winkelmann, B.R., Boehm, B.O., Lucae, S., Penninx, B.W., Smit, J.H., Curhan, G., Mudgal, P., Plenge, R.M., Portas, L., Persico, I., Kirin, M., Wilson, J.F., Mateo Leach, I., van Gilst, W.H., Goel, A., Ongen, H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Imboden, M., von Eckardstein, A., Cucca, F., Nagaraja, R., Piras, M.G., Nauck, M., Schurmann, C., Budde, K., Ernst, F., Farrington, S.M., Theodoratou, E., Prokopenko, I., Stumvoll, M., Jula, A., Perola, M., Salomaa, V., Shin, S.Y., Spector, T.D., Sala, C., Ridker, P.M., Kähönen, M., Viikari, J., Hengstenberg, C., Nelson, C.P., Meschia, J.F., Nalls, M.A., Sharma, P., Singleton, A.B., Kamatani, N., Zeller, T., Burnier, M., Attia, J., Laan, M., Klopp, N., Hillege, H.L., Kloiber, S., Choi, H., Pirastu, M., Tore, S., Probst-Hensch, N.M., Völzke, H., Gudnason, V., Parsa, A., Schmidt, R., Whitfield, J.B., Fornage, M., Gasparini, P., Siscovick, D.S., Pola?ek O., Campbell, H., Rudan, I., Bouatia-Naji, N., Metspalu, A., Loos, R.J., van Duijn, C.M., Borecki, I.B., Ferrucci, L., Gambaro, G., Deary, I.J., Wolffenbuttel, B.H., Chambers, J.C., März, W., Pramstaller, P.P., Snieder, H., Gyllensten, U., Wright, A.F., Navis, G., Watkins, H., Witteman, J.C., Sanna, S., Schipf, S., Dunlop, M.G., Tönjes, A., Ripatti, S., Soranzo, N., Toniolo, D., Chasman, D.I., Raitakari, O., Kao, W.H., Ciullo, M., Fox, C.S., Caulfield, M., Bochud, M., and Gieger, C.
Abstract: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Published: 2013

77. Multiethnic Meta-Analysis of Genome-Wide Association Studies in >100 000 Subjects Identifies 23 Fibrinogen-Associated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease

Author: Sabater-Lleal, Maria, Huang, Jie, Chasman, Daniel, Naitza, Silvia, Dehghan, Abbas, Johnson, Andrew D., Teumer, Alexander, Reiner, Alex P., Folkersen, Lasse, Basu, Saonli, Rudnicka, Alicja R., Trompet, Stella, Mälarstig, Anders, Baumert, Jens, Bis, Joshua C., Guo, Xiuqing, Hottenga, Jouke J., Shin, So-Youn, Lopez, Lorna M., Lahti, Jari, Tanaka, Toshiko, Yanek, Lisa R., Oudot-Mellakh, Tiphaine, Wilson, James F., Navarro, Pau, Huffman, Jennifer E., Zemunik, Tatijana, Redline, Susan, Mehra, Reena, Pulanic, Drazen, Rudan, Igor, Wright, Alan F., Kolcic, Ivana, Polasek, Ozren, Wild, Sarah H., Campbell, Harry, Curb, J. David, Wallace, Robert, Liu, Simin, Eaton, Charles B., Becker, Diane M., Becker, Lewis C., Bandinelli, Stefania, Räikkönen, Katri, Widen, Elisabeth, Palotie, Aarno, Fornage, Myriam, Green, David, Gross, Myron, Davies, Gail, Harris, Sarah E., Liewald, David C., Starr, John M., Williams, Frances M.K., Grant, Peter J., Spector, Timothy D., Strawbridge, Rona J., Silveira, Angela, Sennblad, Bengt, Rivadeneira, Fernando, Uitterlinden, Andre G., Franco, Oscar H., Hofman, Albert, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Yao, Jie, Swords Jenny, Nancy, Haritunians, Talin, McKnight, Barbara, Lumley, Thomas, Taylor, Kent D., Rotter, Jerome I., Psaty, Bruce M., Peters, Annette, Gieger, Christian, Illig, Thomas, Grotevendt, Anne, Homuth, Georg, Völzke, Henry, Kocher, Thomas, Goel, Anuj, Franzosi, Maria Grazia, Seedorf, Udo, Clarke, Robert, Steri, Maristella, Tarasov, Kirill V., Sanna, Serena, Schlessinger, David, Stott, David J., Sattar, Naveed, Buckley, Brendan M., Rumley, Ann, Lowe, Gordon D., McArdle, Wendy L., Chen, Ming-Huei, Tofler, Geoffrey H., Song, Jaejoon, Boerwinkle, Eric, Folsom, Aaron R., Rose, Lynda M., Franco-Cereceda, Anders, Teichert, Martina, Ikram, M. Arfan, Mosley, Thomas H., Bevan, Steve, Dichgans, Martin, Rothwell, Peter M., Sudlow, Cathie L.M., Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Kooner, Jaspal S., Danesh, John, Nelson, Christopher P., Erdmann, Jeanette, Reilly, Muredach P., Kathiresan, Sekar, Schunkert, Heribert, Morange, Pierre-Emmanuel, Ferrucci, Luigi, Eriksson, Johan G., Jacobs, David, Deary, Ian J., Soranzo, Nicole, Witteman, Jacqueline C.M., de Geus, Eco J.C., Tracy, Russell P., Hayward, Caroline, Koenig, Wolfgang, Cucca, Francesco, Jukema, J. Wouter, Eriksson, Per, Seshadri, Sudha, Markus, Hugh S., Watkins, Hugh, Samani, Nilesh J., Wallaschofski, Henri, Smith, Nicholas L., Tregouet, David, Ridker, Paul M, Tang, Weihong, Strachan, David P., Hamsten, Anders, O’Donnell, Christopher J., Sabater-Lleal, Maria, Huang, Jie, Chasman, Daniel, Naitza, Silvia, Dehghan, Abbas, Johnson, Andrew D., Teumer, Alexander, Reiner, Alex P., Folkersen, Lasse, Basu, Saonli, Rudnicka, Alicja R., Trompet, Stella, Mälarstig, Anders, Baumert, Jens, Bis, Joshua C., Guo, Xiuqing, Hottenga, Jouke J., Shin, So-Youn, Lopez, Lorna M., Lahti, Jari, Tanaka, Toshiko, Yanek, Lisa R., Oudot-Mellakh, Tiphaine, Wilson, James F., Navarro, Pau, Huffman, Jennifer E., Zemunik, Tatijana, Redline, Susan, Mehra, Reena, Pulanic, Drazen, Rudan, Igor, Wright, Alan F., Kolcic, Ivana, Polasek, Ozren, Wild, Sarah H., Campbell, Harry, Curb, J. David, Wallace, Robert, Liu, Simin, Eaton, Charles B., Becker, Diane M., Becker, Lewis C., Bandinelli, Stefania, Räikkönen, Katri, Widen, Elisabeth, Palotie, Aarno, Fornage, Myriam, Green, David, Gross, Myron, Davies, Gail, Harris, Sarah E., Liewald, David C., Starr, John M., Williams, Frances M.K., Grant, Peter J., Spector, Timothy D., Strawbridge, Rona J., Silveira, Angela, Sennblad, Bengt, Rivadeneira, Fernando, Uitterlinden, Andre G., Franco, Oscar H., Hofman, Albert, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Yao, Jie, Swords Jenny, Nancy, Haritunians, Talin, McKnight, Barbara, Lumley, Thomas, Taylor, Kent D., Rotter, Jerome I., Psaty, Bruce M., Peters, Annette, Gieger, Christian, Illig, Thomas, Grotevendt, Anne, Homuth, Georg, Völzke, Henry, Kocher, Thomas, Goel, Anuj, Franzosi, Maria Grazia, Seedorf, Udo, Clarke, Robert, Steri, Maristella, Tarasov, Kirill V., Sanna, Serena, Schlessinger, David, Stott, David J., Sattar, Naveed, Buckley, Brendan M., Rumley, Ann, Lowe, Gordon D., McArdle, Wendy L., Chen, Ming-Huei, Tofler, Geoffrey H., Song, Jaejoon, Boerwinkle, Eric, Folsom, Aaron R., Rose, Lynda M., Franco-Cereceda, Anders, Teichert, Martina, Ikram, M. Arfan, Mosley, Thomas H., Bevan, Steve, Dichgans, Martin, Rothwell, Peter M., Sudlow, Cathie L.M., Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Kooner, Jaspal S., Danesh, John, Nelson, Christopher P., Erdmann, Jeanette, Reilly, Muredach P., Kathiresan, Sekar, Schunkert, Heribert, Morange, Pierre-Emmanuel, Ferrucci, Luigi, Eriksson, Johan G., Jacobs, David, Deary, Ian J., Soranzo, Nicole, Witteman, Jacqueline C.M., de Geus, Eco J.C., Tracy, Russell P., Hayward, Caroline, Koenig, Wolfgang, Cucca, Francesco, Jukema, J. Wouter, Eriksson, Per, Seshadri, Sudha, Markus, Hugh S., Watkins, Hugh, Samani, Nilesh J., Wallaschofski, Henri, Smith, Nicholas L., Tregouet, David, Ridker, Paul M, Tang, Weihong, Strachan, David P., Hamsten, Anders, and O’Donnell, Christopher J.
Abstract: Background: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. Methods and results: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013

78. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Author: Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, Gieger, Christian, Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, and Gieger, Christian
Abstract: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Published: 2013

79. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Author: KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Chambers, J.C., Zhang, W., Lord, G.M., van der Harst, P., Lawlor, D.A., Sehmi, J.S., Gale, D.P., Wass, M.N., Ahmadi, K.R., Bakker, S.J., Beckmann, J., Bilo, H.J., Bochud, M., Brown, M.J., Caulfield, M.J., Connell, J.M., Cook, H.T., Cotlarciuc, I., Smith, G.D., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Farrall, M., Ferrucci, L., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Hedblad, B., van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., Johnson, T., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Li, Y., Loos, R.J., Luan, J., Luttropp, K., Maréchal, C., Melander, O., Munroe, P.B., Nordfors, L., Parsa, A., Peltonen, L., Penninx, B.W., Perucha, E., Pouta, A., Prokopenko, I., Roderick, P.J., Ruokonen, A., Samani, N.J., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Shuldiner, A.R., Sjögren, M., Smit, J.H., Snieder, H., Soranzo, N., Spector, T.D., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Tanaka, T., Ubink-Veltmaat, L.J., Uda, M., Vollenweider, P., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Wareham, N.J., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., Mooser, V., Abecasis, G.R., Lightstone, L., Scott, J., Navis, G., Elliott, P., Kooner, J.S., Köttgen, A., Pattaro, C., Böger, C.A., Fuchsberger, C., Olden, M., Glazer, N.L., Gao, X., Yang, Q., Smith, A.V., O'Connell, J.R., Li, M., Schmidt, H., Isaacs, A., Ketkar, S., Hwang, S.J., Johnson, A.D., Dehghan, A., Teumer, A., Paré, G., Atkinson, E.J., Zeller, T., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Hayward, C., Aspelund, T., Eiriksdottir, G., Launer, L.J., Harris, T.B., Rampersaud, E., Mitchell, B.D., Arking, D.E., Boerwinkle, E., Struchalin, M., Cavalieri, M., Singleton, A., Giallauria, F., Metter, J., de Boer, I.H., Haritunians, T., Lumley, T., Siscovick, D., Psaty, B.M., Zillikens, M.C., Oostra, B.A., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Schillert, A., Ziegler, A., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Illig, T., Klopp, N., Meisinger, C., Wichmann, H.E., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, Å., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Schreiber, S., Aulchenko, Y.S., Felix, J.F., Rivadeneira, F., Uitterlinden, A.G., Hofman, A., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Völzke, H., Kroemer, H.K., Nauck, M., Völker, U., Polasek, O., Vitart, V., Badola, S., Parker, A.N., Ridker, P.M., Kardia, S.L., Blankenberg, S., Liu, Y., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Gudnason, V., Coresh, J., Schmidt, R., Shlipak, M.G., van Duijn, C.M., Borecki, I., Krämer, B.K., Rudan, I., Gyllensten, U., Wilson, J.F., Witteman, J.C., Pramstaller, P.P., Rettig, R., Hastie, N., Chasman, D.I., Kao, W.H., Heid, I.M., Fox, C.S., Albrecht, E., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, M., Haller, T., Kutalik, Z., Shi, J., Middelberg, P.S., Gaffo, A.L., Pirastu, N., Li, G., Huffman, J., Yengo, L., Zhao, J.H., Demirkan, A., Feitosa, M.F., Liu, X., Malerba, G., Lopez, L.M., Li, X., Kleber, M.E., Hicks, A.A., Nolte, I.M., Johansson, A., Murgia, F., Peden, J.F., Steri, M., Tenesa, A., Salo, P., Mangino, M., Rose, L.M., Lehtimäki, T., Woodward, O.M., Okada, Y., Tin, A., Müller, C., Oldmeadow, C., Putku, M., Czamara, D., Kraft, P., Frogheri, L., Thun, G.A., Grotevendt, A., Gislason, G.K., McArdle, P., Schallert, M., Martin, N.G., Montgomery, G.W., Kubo, M., Nakamura, Y., Jacobs, D.R., Liu, K., D'Adamo, P., Ulivi, S., Rotter, J.I., Navaro, P., Balkau, B., Froguel, P., Esko, T., Salumets, A., Khaw, K.T., Langenberg, C., Kraja, A., Zhang, Q., Scott, R.J., Holliday, E.G., Org, E., Viigimaa, M., Bandinelli, S., Metter, J.E., Lupo, A., Trabetti, E., Sorice, R., Döring, A., Lattka, E., Strauch, K., Theis, F., Waldenberger, M., Davies, G., Gow, A.J., Bruinenberg, M., Stolk, R.P., Winkelmann, B.R., Boehm, B.O., Lucae, S., Curhan, G., Mudgal, P., Plenge, R.M., Portas, L., Persico, I., Kirin, M., Mateo Leach, I., van Gilst, W.H., Goel, A., Ongen, H., von Eckardstein, A., Cucca, F., Nagaraja, R., Piras, M.G., Schurmann, C., Budde, K., Ernst, F., Farrington, S.M., Theodoratou, E., Jula, A., Perola, M., Salomaa, V., Shin, S.Y., Sala, C., Kähönen, M., Viikari, J., Hengstenberg, C., Nelson, C.P., Meschia, J.F., Nalls, M.A., Sharma, P., Singleton, A.B., Kamatani, N., Burnier, M., Attia, J., Laan, M., Hillege, H.L., Kloiber, S., Choi, H., Pirastu, M., Tore, S., Whitfield, J.B., Fornage, M., Gasparini, P., Siscovick, D.S., Bouatia-Naji, N., Metspalu, A., Borecki, I.B., Gambaro, G., Deary, I.J., Wolffenbuttel, B.H., März, W., Watkins, H., Schipf, S., Dunlop, M.G., Ripatti, S., Toniolo, D., Raitakari, O., Ciullo, M., Caulfield, M., Gieger, C., Sim, X., Go, M.J., Wu, J.Y., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, S.C., Wong, T.Y., Liu, J., Young, T.L., Aung, T., Seielstad, M., Teo, Y.Y., Kim, Y.J., Lee, J.Y., Han, B.G., Kang, D., Chen, C.H., Tsai, F.J., Chang, L.C., Fann, S.J., Mei, H., Rao, D.C., Hixson, J.E., Chen, S., Katsuya, T., Isono, M., Ogihara, T., Yamamoto, K., Kato, N., He, J., Chen, Y.T., Cho, Y.S., Tai, E.S., KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Chambers, J.C., Zhang, W., Lord, G.M., van der Harst, P., Lawlor, D.A., Sehmi, J.S., Gale, D.P., Wass, M.N., Ahmadi, K.R., Bakker, S.J., Beckmann, J., Bilo, H.J., Bochud, M., Brown, M.J., Caulfield, M.J., Connell, J.M., Cook, H.T., Cotlarciuc, I., Smith, G.D., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Farrall, M., Ferrucci, L., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Hedblad, B., van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., Johnson, T., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Li, Y., Loos, R.J., Luan, J., Luttropp, K., Maréchal, C., Melander, O., Munroe, P.B., Nordfors, L., Parsa, A., Peltonen, L., Penninx, B.W., Perucha, E., Pouta, A., Prokopenko, I., Roderick, P.J., Ruokonen, A., Samani, N.J., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Shuldiner, A.R., Sjögren, M., Smit, J.H., Snieder, H., Soranzo, N., Spector, T.D., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Tanaka, T., Ubink-Veltmaat, L.J., Uda, M., Vollenweider, P., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Wareham, N.J., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., Mooser, V., Abecasis, G.R., Lightstone, L., Scott, J., Navis, G., Elliott, P., Kooner, J.S., Köttgen, A., Pattaro, C., Böger, C.A., Fuchsberger, C., Olden, M., Glazer, N.L., Gao, X., Yang, Q., Smith, A.V., O'Connell, J.R., Li, M., Schmidt, H., Isaacs, A., Ketkar, S., Hwang, S.J., Johnson, A.D., Dehghan, A., Teumer, A., Paré, G., Atkinson, E.J., Zeller, T., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Hayward, C., Aspelund, T., Eiriksdottir, G., Launer, L.J., Harris, T.B., Rampersaud, E., Mitchell, B.D., Arking, D.E., Boerwinkle, E., Struchalin, M., Cavalieri, M., Singleton, A., Giallauria, F., Metter, J., de Boer, I.H., Haritunians, T., Lumley, T., Siscovick, D., Psaty, B.M., Zillikens, M.C., Oostra, B.A., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Schillert, A., Ziegler, A., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Illig, T., Klopp, N., Meisinger, C., Wichmann, H.E., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, Å., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Schreiber, S., Aulchenko, Y.S., Felix, J.F., Rivadeneira, F., Uitterlinden, A.G., Hofman, A., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Völzke, H., Kroemer, H.K., Nauck, M., Völker, U., Polasek, O., Vitart, V., Badola, S., Parker, A.N., Ridker, P.M., Kardia, S.L., Blankenberg, S., Liu, Y., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Gudnason, V., Coresh, J., Schmidt, R., Shlipak, M.G., van Duijn, C.M., Borecki, I., Krämer, B.K., Rudan, I., Gyllensten, U., Wilson, J.F., Witteman, J.C., Pramstaller, P.P., Rettig, R., Hastie, N., Chasman, D.I., Kao, W.H., Heid, I.M., Fox, C.S., Albrecht, E., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, M., Haller, T., Kutalik, Z., Shi, J., Middelberg, P.S., Gaffo, A.L., Pirastu, N., Li, G., Huffman, J., Yengo, L., Zhao, J.H., Demirkan, A., Feitosa, M.F., Liu, X., Malerba, G., Lopez, L.M., Li, X., Kleber, M.E., Hicks, A.A., Nolte, I.M., Johansson, A., Murgia, F., Peden, J.F., Steri, M., Tenesa, A., Salo, P., Mangino, M., Rose, L.M., Lehtimäki, T., Woodward, O.M., Okada, Y., Tin, A., Müller, C., Oldmeadow, C., Putku, M., Czamara, D., Kraft, P., Frogheri, L., Thun, G.A., Grotevendt, A., Gislason, G.K., McArdle, P., Schallert, M., Martin, N.G., Montgomery, G.W., Kubo, M., Nakamura, Y., Jacobs, D.R., Liu, K., D'Adamo, P., Ulivi, S., Rotter, J.I., Navaro, P., Balkau, B., Froguel, P., Esko, T., Salumets, A., Khaw, K.T., Langenberg, C., Kraja, A., Zhang, Q., Scott, R.J., Holliday, E.G., Org, E., Viigimaa, M., Bandinelli, S., Metter, J.E., Lupo, A., Trabetti, E., Sorice, R., Döring, A., Lattka, E., Strauch, K., Theis, F., Waldenberger, M., Davies, G., Gow, A.J., Bruinenberg, M., Stolk, R.P., Winkelmann, B.R., Boehm, B.O., Lucae, S., Curhan, G., Mudgal, P., Plenge, R.M., Portas, L., Persico, I., Kirin, M., Mateo Leach, I., van Gilst, W.H., Goel, A., Ongen, H., von Eckardstein, A., Cucca, F., Nagaraja, R., Piras, M.G., Schurmann, C., Budde, K., Ernst, F., Farrington, S.M., Theodoratou, E., Jula, A., Perola, M., Salomaa, V., Shin, S.Y., Sala, C., Kähönen, M., Viikari, J., Hengstenberg, C., Nelson, C.P., Meschia, J.F., Nalls, M.A., Sharma, P., Singleton, A.B., Kamatani, N., Burnier, M., Attia, J., Laan, M., Hillege, H.L., Kloiber, S., Choi, H., Pirastu, M., Tore, S., Whitfield, J.B., Fornage, M., Gasparini, P., Siscovick, D.S., Bouatia-Naji, N., Metspalu, A., Borecki, I.B., Gambaro, G., Deary, I.J., Wolffenbuttel, B.H., März, W., Watkins, H., Schipf, S., Dunlop, M.G., Ripatti, S., Toniolo, D., Raitakari, O., Ciullo, M., Caulfield, M., Gieger, C., Sim, X., Go, M.J., Wu, J.Y., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, S.C., Wong, T.Y., Liu, J., Young, T.L., Aung, T., Seielstad, M., Teo, Y.Y., Kim, Y.J., Lee, J.Y., Han, B.G., Kang, D., Chen, C.H., Tsai, F.J., Chang, L.C., Fann, S.J., Mei, H., Rao, D.C., Hixson, J.E., Chen, S., Katsuya, T., Isono, M., Ogihara, T., Yamamoto, K., Kato, N., He, J., Chen, Y.T., Cho, Y.S., and Tai, E.S.
Abstract: Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.
Published: 2012

80. Relation of insulin‐like growth factor‐I and IGF binding protein 3 with markers of inflammation: results of a population‐based study

Author: Lohr, Johannes, primary, Grotevendt, Anne, additional, Nauck, Matthias, additional, Völzke, Henry, additional, Wallaschofski, Henri, additional, and Friedrich, Nele, additional
Published: 2013
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81. Partially desulfated heparin modulates the interaction between anti- protamine/ heparin antibodies and platelets.

Author: Jouni, Rabie, Zöllner, Heike, Khadour, Ahmad, Wesche, Jan, Grotevendt, Anne, Brandt, Sven, Delcea, Mihaela, Krauel, Krystin, Schwertz, Hansjörg, Sachs, Ulrich J., Greinacher, Andreas, and Bakchoul, Tamam
Published: 2016
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82. Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study

Author: Holtfreter, Birte, primary, Richter, Stefanie, additional, Kocher, Thomas, additional, Dörr, Marcus, additional, Völzke, Henry, additional, Ittermann, Till, additional, Obst, Anne, additional, Schäper, Christoph, additional, John, Ulrich, additional, Meisel, Peter, additional, Grotevendt, Anne, additional, Felix, Stephan B., additional, Ewert, Ralf, additional, and Gläser, Sven, additional
Published: 2012
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83. Short-Term Changes of the Urine Metabolome After Bariatric Surgery

Author: Friedrich, Nele, primary, Budde, Kathrin, additional, Wolf, Tillmann, additional, Jungnickel, Arne, additional, Grotevendt, Anne, additional, Dreßler, Miriam, additional, Völzke, Henry, additional, Blüher, Matthias, additional, Nauck, Matthias, additional, Lohmann, Tobias, additional, and Wallaschofksi, Henri, additional
Published: 2012
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84. Short-term changes of the urine metabolome after bariatric surgery

Author: Friedrich, N, primary, Budde, K, additional, Wolf, T, additional, Jungnickel, A, additional, Grotevendt, A, additional, Dreßler, M, additional, Völzke, H, additional, Blüher, M, additional, Nauck, M, additional, Lohmann, T, additional, and Wallaschofski, H, additional
Published: 2012
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85. Ethylene-Promoted versus Ethylene-Free Enyne Metathesis

Author: Grotevendt, Anne G. D., primary, Lummiss, Justin A. M., additional, Mastronardi, Melanie L., additional, and Fogg, Deryn E., additional
Published: 2011
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86. A Practical Palladium-Catalyzed Telomerization for the Synthesis of Functionalized Alcohols

Author: Jackstell, Ralf, primary, Grotevendt, Anne, additional, Andreu, Mario Gomez, additional, and Beller, Matthias, additional
Published: 2009
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87. Efficient and Selective Telomerization of 1,3‐Butadiene with Diols Catalyzed by Palladium–Carbene Complexes

Author: Grotevendt, Anne, primary, Jackstell, Ralf, additional, Michalik, Dirk, additional, Gomez, Mario, additional, and Beller, Matthias, additional
Published: 2009
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88. ChemInform Abstract: Development of Palladium—Carbene Catalysts for Telomerization and Dimerization of 1,3‐Dienes: Form Basic Research to Industrial Applications.

Author: Clement, Nicolas D., primary, Routaboul, Lucie, additional, Grotevendt, Anne, additional, Jackstell, Ralf, additional, and Beller, Matthias, additional
Published: 2008
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89. Development of Palladium–Carbene Catalysts for Telomerization and Dimerization of 1,3‐Dienes: From Basic Research to Industrial Applications

Author: Clement, Nicolas D., primary, Routaboul, Lucie, additional, Grotevendt, Anne, additional, Jackstell, Ralf, additional, and Beller, Matthias, additional
Published: 2008
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90. Efficient catalysts for telomerization of butadiene with amines

Author: Grotevendt, Anne, primary, Bartolome, Maribel, additional, Nielsen, David J., additional, Spannenberg, Anke, additional, Jackstell, Ralf, additional, Cavell, Kingsley J., additional, Oro, Luis A., additional, and Beller, Matthias, additional
Published: 2007
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91. Development of a General and Efficient Iron‐Catalyzed Epoxidation with Hydrogen Peroxide as Oxidant.

Author: Bitterlich, Bianca, primary, Anilkumar, Gopinathan, additional, Gelalcha, Feyissa Gadissa, additional, Spilker, Bjoern, additional, Grotevendt, Anne, additional, Jackstell, Ralf, additional, Tse, Man Kin, additional, and Beller, Matthias, additional
Published: 2007
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92. Synthesis of a New Chiral N,N,N-Tridentate Pyridinebisimidazole Ligand Library and Its Application in Ru-Catalyzed Asymmetric Epoxidation.

Author: Bhor, Santosh, primary, Anilkumar, Gopinathan, additional, Tse, Man Kin, additional, Klawonn, Markus, additional, Doebler, Christian, additional, Bitterlich, Bianca, additional, Grotevendt, Anne, additional, and Beller, Matthias, additional
Published: 2005
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93. Synthesis of a New Chiral N,N,N-Tridentate Pyridinebisimidazoline Ligand Library and Its Application in Ru-Catalyzed Asymmetric Epoxidation

Author: Bhor, S., Anilkumar, G., Tse, M. K., Klawonn, M., Dobler, C., Bitterlich, B., Grotevendt, A., and Beller, M.
Abstract: A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (>99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins.
Published: 2005

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

Author: Huffman JE, Albrecht E, Teumer A, Mangino M, Kapur K, Johnson T, Kutalik Z, Pirastu N, Pistis G, Lopez LM, Haller T, Salo P, Goel A, Li M, Tanaka T, Dehghan A, Ruggiero D, Malerba G, Smith AV, Nolte IM, Portas L, Phipps-Green A, Boteva L, Navarro P, Johansson A, Hicks AA, Polasek O, Esko T, Peden JF, Harris SE, Murgia F, Wild SH, Tenesa A, Tin A, Mihailov E, Grotevendt A, Gislason GK, Coresh J, D'Adamo P, Ulivi S, Vollenweider P, Waeber G, Campbell S, Kolcic I, Fisher K, Viigimaa M, Metter JE, Masciullo C, Trabetti E, Bombieri C, Sorice R, Döring A, Reischl E, Strauch K, Hofman A, Uitterlinden AG, Waldenberger M, Wichmann HE, Davies G, Gow AJ, Dalbeth N, Stamp L, Smit JH, Kirin M, Nagaraja R, Nauck M, Schurmann C, Budde K, Farrington SM, Theodoratou E, Jula A, Salomaa V, Sala C, Hengstenberg C, Burnier M, Mägi R, Klopp N, Kloiber S, Schipf S, Ripatti S, Cabras S, Soranzo N, Homuth G, Nutile T, Munroe PB, Hastie N, Campbell H, Rudan I, Cabrera C, Haley C, Franco OH, Merriman TR, Gudnason V, Pirastu M, Penninx BW, Snieder H, Metspalu A, Ciullo M, Pramstaller PP, van Duijn CM, Ferrucci L, Gambaro G, Deary IJ, Dunlop MG, Wilson JF, Gasparini P, Gyllensten U, Spector TD, Wright AF, Hayward C, Watkins H, Perola M, Bochud M, Kao WH, Caulfield M, Toniolo D, Völzke H, Gieger C, Köttgen A, and Vitart V
Subjects: ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters genetics, Antigens, Nuclear genetics, Body Mass Index, Edar Receptor genetics, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Gout genetics, Gout pathology, Humans, Linear Models, Male, Membrane Glycoproteins genetics, Neoplasm Proteins genetics, Nerve Tissue Proteins genetics, Obesity genetics, Obesity pathology, Overweight genetics, Oxidoreductases Acting on Sulfur Group Donors genetics, Polymorphism, Single Nucleotide, Risk Factors, Uric Acid blood
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
Published: 2015
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95. Acquired hemophilia with inhibitors presenting as an emergency: misinterpretation of clotting results during direct oral anticoagulation.

Author: Sümnig A, Grotevendt A, Westphal A, Fiene M, Greinacher A, and Thiele T
Subjects: Administration, Oral, Aged, Anticoagulants administration & dosage, Anticoagulants adverse effects, Diagnosis, Differential, Female, Hemophilia A prevention & control, Humans, Rivaroxaban, Treatment Outcome, Blood Coagulation Tests, Diagnostic Errors prevention & control, Emergency Medical Services methods, Hemophilia A chemically induced, Hemophilia A diagnosis, Morpholines administration & dosage, Morpholines adverse effects, Thiophenes administration & dosage, Thiophenes adverse effects
Abstract: Background: Direct oral anticoagulants (DOACs) were recently introduced and are being increasingly prescribed. Most DOACs alter the values of traditional coagulation tests, such as the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT). Although vitamin K antagonists raise the INR value to an extent that mirrors their anticoagulant effect, DOACs do not, in general, alter standard clotting values in any consistent way. Thus, there is a risk that abnormal INR and aPTT values can be misinterpreted., Case Illustration: A woman taking rivaroxaban, a DOAC, presented with ileus and was scheduled for urgent surgery. A prolonged aPTT was, at first, wrongly attributed to rivaroxaban, delaying the correct diagnosis of autoantibody-associated acquired hemophilia (a rare condition with incidence, 1.34-1.48 cases per million people per year). The patient had a history of unusually intense bleeding in the skin and mucous membranes during anticoagulant treatment. Her aPTT had been prolonged even before any anticoagulants were taken., Course: The operation was delayed to await the elimination of rivaroxaban. The aPTT was still prolonged 24 hours later. The diagnosis of autoantibody-associated acquired hemophilia was suspected and then confirmed by the measurement of a factor VIII residual activity of 1% and the demonstration of factor VIII inhibition at an intensity of 9.2 Bethesda units per mL., Conclusion: The causes of abnormal clotting test results must be clarified before beginning anticoagulant therapy. Unusually intense bleeding during oral anticoagulation should arouse suspicion of a previously undiagnosed acquired coagulopathy, e.g., antibody-associated acquired hemophilia.
Published: 2014
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96. Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

Author: Holtfreter B, Richter S, Kocher T, Dörr M, Völzke H, Ittermann T, Obst A, Schäper C, John U, Meisel P, Grotevendt A, Felix SB, Ewert R, and Gläser S
Subjects: Adult, Age Factors, Aged, Aged, 80 and over, C-Reactive Protein metabolism, Carbon Monoxide analysis, Carbon Monoxide chemistry, Cross-Sectional Studies, Female, Fibrinogen metabolism, Humans, Inflammation, Linear Models, Lung physiopathology, Lung Diseases complications, Male, Middle Aged, Periodontitis complications, Plethysmography, Prospective Studies, Respiration, Respiratory Function Tests, Sex Factors, Smoking adverse effects, Spirometry, Lung Diseases physiopathology, Periodontitis physiopathology
Abstract: This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.
Published: 2013
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97. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

Author: Sabater-Lleal M, Huang J, Chasman D, Naitza S, Dehghan A, Johnson AD, Teumer A, Reiner AP, Folkersen L, Basu S, Rudnicka AR, Trompet S, Mälarstig A, Baumert J, Bis JC, Guo X, Hottenga JJ, Shin SY, Lopez LM, Lahti J, Tanaka T, Yanek LR, Oudot-Mellakh T, Wilson JF, Navarro P, Huffman JE, Zemunik T, Redline S, Mehra R, Pulanic D, Rudan I, Wright AF, Kolcic I, Polasek O, Wild SH, Campbell H, Curb JD, Wallace R, Liu S, Eaton CB, Becker DM, Becker LC, Bandinelli S, Räikkönen K, Widen E, Palotie A, Fornage M, Green D, Gross M, Davies G, Harris SE, Liewald DC, Starr JM, Williams FM, Grant PJ, Spector TD, Strawbridge RJ, Silveira A, Sennblad B, Rivadeneira F, Uitterlinden AG, Franco OH, Hofman A, van Dongen J, Willemsen G, Boomsma DI, Yao J, Swords Jenny N, Haritunians T, McKnight B, Lumley T, Taylor KD, Rotter JI, Psaty BM, Peters A, Gieger C, Illig T, Grotevendt A, Homuth G, Völzke H, Kocher T, Goel A, Franzosi MG, Seedorf U, Clarke R, Steri M, Tarasov KV, Sanna S, Schlessinger D, Stott DJ, Sattar N, Buckley BM, Rumley A, Lowe GD, McArdle WL, Chen MH, Tofler GH, Song J, Boerwinkle E, Folsom AR, Rose LM, Franco-Cereceda A, Teichert M, Ikram MA, Mosley TH, Bevan S, Dichgans M, Rothwell PM, Sudlow CL, Hopewell JC, Chambers JC, Saleheen D, Kooner JS, Danesh J, Nelson CP, Erdmann J, Reilly MP, Kathiresan S, Schunkert H, Morange PE, Ferrucci L, Eriksson JG, Jacobs D, Deary IJ, Soranzo N, Witteman JC, de Geus EJ, Tracy RP, Hayward C, Koenig W, Cucca F, Jukema JW, Eriksson P, Seshadri S, Markus HS, Watkins H, Samani NJ, Wallaschofski H, Smith NL, Tregouet D, Ridker PM, Tang W, Strachan DP, Hamsten A, and O'Donnell CJ
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Black People genetics, Black People statistics & numerical data, Cardiovascular Diseases metabolism, Coronary Artery Disease ethnology, Coronary Artery Disease genetics, Coronary Artery Disease metabolism, Female, Genetic Predisposition to Disease ethnology, Hispanic or Latino genetics, Hispanic or Latino statistics & numerical data, Humans, Male, Middle Aged, Myocardial Infarction ethnology, Myocardial Infarction genetics, Myocardial Infarction metabolism, Polymorphism, Single Nucleotide genetics, Risk Factors, Stroke ethnology, Stroke genetics, Stroke metabolism, Venous Thromboembolism ethnology, Venous Thromboembolism genetics, Venous Thromboembolism metabolism, White People genetics, White People statistics & numerical data, Young Adult, Cardiovascular Diseases ethnology, Cardiovascular Diseases genetics, Fibrinogen genetics, Fibrinogen metabolism, Genetic Loci genetics, Genome-Wide Association Study
Abstract: Background: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation., Methods and Results: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism., Conclusions: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013
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98. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Author: Köttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, Pistis G, Ruggiero D, O'Seaghdha CM, Haller T, Yang Q, Tanaka T, Johnson AD, Kutalik Z, Smith AV, Shi J, Struchalin M, Middelberg RP, Brown MJ, Gaffo AL, Pirastu N, Li G, Hayward C, Zemunik T, Huffman J, Yengo L, Zhao JH, Demirkan A, Feitosa MF, Liu X, Malerba G, Lopez LM, van der Harst P, Li X, Kleber ME, Hicks AA, Nolte IM, Johansson A, Murgia F, Wild SH, Bakker SJ, Peden JF, Dehghan A, Steri M, Tenesa A, Lagou V, Salo P, Mangino M, Rose LM, Lehtimäki T, Woodward OM, Okada Y, Tin A, Müller C, Oldmeadow C, Putku M, Czamara D, Kraft P, Frogheri L, Thun GA, Grotevendt A, Gislason GK, Harris TB, Launer LJ, McArdle P, Shuldiner AR, Boerwinkle E, Coresh J, Schmidt H, Schallert M, Martin NG, Montgomery GW, Kubo M, Nakamura Y, Tanaka T, Munroe PB, Samani NJ, Jacobs DR Jr, Liu K, D'Adamo P, Ulivi S, Rotter JI, Psaty BM, Vollenweider P, Waeber G, Campbell S, Devuyst O, Navarro P, Kolcic I, Hastie N, Balkau B, Froguel P, Esko T, Salumets A, Khaw KT, Langenberg C, Wareham NJ, Isaacs A, Kraja A, Zhang Q, Wild PS, Scott RJ, Holliday EG, Org E, Viigimaa M, Bandinelli S, Metter JE, Lupo A, Trabetti E, Sorice R, Döring A, Lattka E, Strauch K, Theis F, Waldenberger M, Wichmann HE, Davies G, Gow AJ, Bruinenberg M, Stolk RP, Kooner JS, Zhang W, Winkelmann BR, Boehm BO, Lucae S, Penninx BW, Smit JH, Curhan G, Mudgal P, Plenge RM, Portas L, Persico I, Kirin M, Wilson JF, Mateo Leach I, van Gilst WH, Goel A, Ongen H, Hofman A, Rivadeneira F, Uitterlinden AG, Imboden M, von Eckardstein A, Cucca F, Nagaraja R, Piras MG, Nauck M, Schurmann C, Budde K, Ernst F, Farrington SM, Theodoratou E, Prokopenko I, Stumvoll M, Jula A, Perola M, Salomaa V, Shin SY, Spector TD, Sala C, Ridker PM, Kähönen M, Viikari J, Hengstenberg C, Nelson CP, Meschia JF, Nalls MA, Sharma P, Singleton AB, Kamatani N, Zeller T, Burnier M, Attia J, Laan M, Klopp N, Hillege HL, Kloiber S, Choi H, Pirastu M, Tore S, Probst-Hensch NM, Völzke H, Gudnason V, Parsa A, Schmidt R, Whitfield JB, Fornage M, Gasparini P, Siscovick DS, Polašek O, Campbell H, Rudan I, Bouatia-Naji N, Metspalu A, Loos RJ, van Duijn CM, Borecki IB, Ferrucci L, Gambaro G, Deary IJ, Wolffenbuttel BH, Chambers JC, März W, Pramstaller PP, Snieder H, Gyllensten U, Wright AF, Navis G, Watkins H, Witteman JC, Sanna S, Schipf S, Dunlop MG, Tönjes A, Ripatti S, Soranzo N, Toniolo D, Chasman DI, Raitakari O, Kao WH, Ciullo M, Fox CS, Caulfield M, Bochud M, and Gieger C
Subjects: Analysis of Variance, Gene Frequency, Genome-Wide Association Study, Glucose metabolism, Gout blood, Humans, Inhibins genetics, Inhibins metabolism, Polymorphism, Single Nucleotide genetics, White People, Genetic Loci genetics, Gout genetics, Signal Transduction genetics, Uric Acid blood
Abstract: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Published: 2013
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99. Short-term changes of the urine metabolome after bariatric surgery.

Author: Friedrich N, Budde K, Wolf T, Jungnickel A, Grotevendt A, Dressler M, Völzke H, Blüher M, Nauck M, Lohmann T, and Wallaschofksi H
Subjects: Adult, Case-Control Studies, Humans, Magnetic Resonance Spectroscopy, Middle Aged, Time Factors, Young Adult, Bariatric Surgery, Metabolome, Obesity surgery, Obesity urine
Abstract: Bariatric surgery leads to a loss of excess weight and to a remission of diabetes in a majority of patients. In an attempt to explain these underlying mechanisms, a broad range of metabolic alterations have been suggested. We aimed to investigate short-term changes in the urinary metabolome after bariatric surgery. Data for 50 patients who underwent bariatric surgery at the Municipal Hospital of Dresden-Neustadt, Germany, were used. Healthy controls were selected from the Study of Health in Pomerania. Non-fasting, spontaneous urine samples were collected, (1)H NMR spectroscopic analysis was performed, and metabolites were quantified (Chenomx NMR suite). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) models were carried out (pre-operative versus controls, and post-operative versus controls). On the basis of the urine metabolome separations between pre-operative (predictive ability Q2Y=85.6%; total explained variance R2X=58.3%), or post-operative (Q2Y=82.1%; R2X=44.4%) and controls were possible. Metabolites including hippuric acid, 3-hydroxybutyrate, 2-hydroxyisobutyrate, and trigonelline, were altered among patients. In obese patients, 2-hydroxyisobutyrate levels were higher, whereas trigonelline and hippuric acid levels were lower than in controls. The highest levels of 3-hydroxybutyrate were found in post-operative samples, whereas the metabolite was not present in controls, and only at low levels in pre-operative samples. In conclusion, we demonstrated that the urinary metabotype differs between obese patients and healthy controls. The metabolic alterations identified after bariatric procedures increase our knowledge about the metabolic traits associated with weight reduction. Whether urinary metabotypes might be used for early prediction of a successful bariatric procedure should be evaluated in long-term observations.
Published: 2012
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100. Development of palladium-carbene catalysts for telomerization and dimerization of 1,3-dienes: from basic research to industrial applications.

Author: Clement ND, Routaboul L, Grotevendt A, Jackstell R, and Beller M
Subjects: Alkadienes chemistry, Catalysis, Crystallography, X-Ray, Dimerization, Hydrogenation, Methane chemistry, Models, Molecular, Molecular Structure, Organometallic Compounds chemical synthesis, Pilot Projects, Alkadienes chemical synthesis, Chemical Industry methods, Methane analogs & derivatives, Organometallic Compounds chemistry, Palladium chemistry
Abstract: The following account summarises recent developments in the area of palladium-catalysed telomerisation and dimerisation reactions of 1,3-dienes. The most active types of catalyst, palladium-carbene complexes, were tested in pilot plant and proved to be industrially viable.
Published: 2008
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