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Your search keyword '"Rice, Kenneth M."' showing total 11 results
Start Over Author "Rice, Kenneth M." Journal nature communications
11 results on '"Rice, Kenneth M."'

1. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

Author

Scholz, Markus, Horn, Katrin, Pott, Janne, Wuttke, Matthias, Kühnapfel, Andreas, Nasr, M. Kamal, Kirsten, Holger, Li, Yong, Hoppmann, Anselm, Gorski, Mathias, Ghasemi, Sahar, Li, Man, Tin, Adrienne, Chai, Jin-Fang, Cocca, Massimiliano, Wang, Judy, Nutile, Teresa, Akiyama, Masato, Åsvold, Bjørn Olav, Bansal, Nisha, Biggs, Mary L., Boutin, Thibaud, Brenner, Hermann, Brumpton, Ben, Burkhardt, Ralph, Cai, Jianwen, Campbell, Archie, Campbell, Harry, Chalmers, John, Chasman, Daniel I., Chee, Miao Ling, Chee, Miao Li, Chen, Xu, Cheng, Ching-Yu, Cifkova, Renata, Daviglus, Martha, Delgado, Graciela, Dittrich, Katalin, Edwards, Todd L., Endlich, Karlhans, Michael Gaziano, J., Giri, Ayush, Giulianini, Franco, Gordon, Scott D., Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hartman, Catharina A., Hayward, Caroline, Heid, Iris M., Hellwege, Jacklyn N., Holleczek, Bernd, Holm, Hilma, Hutri-Kähönen, Nina, Hveem, Kristian, Isermann, Berend, Jonas, Jost B., Joshi, Peter K., Kamatani, Yoichiro, Kanai, Masahiro, Kastarinen, Mika, Khor, Chiea Chuen, Kiess, Wieland, Kleber, Marcus E., Körner, Antje, Kovacs, Peter, Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kuokkanen, Mikko, Kähönen, Mika, Lange, Leslie A., Lash, James P., Lehtimäki, Terho, Li, Hengtong, Lin, Bridget M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K. E., Martin, Nicholas G., Matsuda, Koichi, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., März, Winfried, Nauck, Matthias, Nikus, Kjell, Nolte, Ilja M., Noordam, Raymond, Okada, Yukinori, Olafsson, Isleifur, Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Perola, Markus, Pirastu, Nicola, Polasek, Ozren, Porteous, David J., Poulain, Tanja, Psaty, Bruce M., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Rasheed, Humaira, Reilly, Dermot F., Rice, Kenneth M., Richmond, Anne, Ridker, Paul M., Rotter, Jerome I., Rudan, Igor, Sabanayagam, Charumathi, Salomaa, Veikko, Schneiderman, Neil, Schöttker, Ben, Sims, Mario, Snieder, Harold, Stark, Klaus J., Stefansson, Kari, Stocker, Hannah, Stumvoll, Michael, Sulem, Patrick, Sveinbjornsson, Gardar, Svensson, Per O., Tai, E-Shyong, Taylor, Kent D., Tayo, Bamidele O., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomas, Laurent F., Tremblay, Johanne, Tönjes, Anke, van der Most, Peter J., Vitart, Veronique, Völker, Uwe, Wang, Ya Xing, Wang, Chaolong, Wei, Wen Bin, Whitfield, John B., Wild, Sarah H., Wilson, James F., Winkler, Thomas W., Wong, Tien-Yin, Woodward, Mark, Sim, Xueling, Chu, Audrey Y., Feitosa, Mary F., Thorsteinsdottir, Unnur, Hung, Adriana M., Teumer, Alexander, Franceschini, Nora, Parsa, Afshin, Köttgen, Anna, Schlosser, Pascal, and Pattaro, Cristian

Published
2024
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2. Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes

Author

Halford, Jennifer L, Morrill, Valerie N, Choi, Seung Hoan, Jurgens, Sean J, Melloni, Giorgio, Marston, Nicholas A, Weng, Lu-Chen, Nauffal, Victor, Hall, Amelia W, Gunn, Sophia, Austin-Tse, Christina A, Pirruccello, James P, Khurshid, Shaan, Rehm, Heidi L, Benjamin, Emelia J, Boerwinkle, Eric, Brody, Jennifer A, Correa, Adolfo, Fornwalt, Brandon K, Gupta, Namrata, Haggerty, Christopher M, Harris, Stephanie, Heckbert, Susan R, Hong, Charles C, Kooperberg, Charles, Lin, Henry J, Loos, Ruth JF, Mitchell, Braxton D, Morrison, Alanna C, Post, Wendy, Psaty, Bruce M, Redline, Susan, Rice, Kenneth M, Rich, Stephen S, Rotter, Jerome I, Schnatz, Peter F, Soliman, Elsayed Z, Sotoodehnia, Nona, Wong, Eugene K, Sabatine, Marc S, Ruff, Christian T, Lunetta, Kathryn L, Ellinor, Patrick T, and Lubitz, Steven A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Disease Susceptibility, Endophenotypes, Humans, Long QT Syndrome, Virulence, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P

Published
2022

3. Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology

Author

Sajuthi, Satria P, Everman, Jamie L, Jackson, Nathan D, Saef, Benjamin, Rios, Cydney L, Moore, Camille M, Mak, Angel CY, Eng, Celeste, Fairbanks-Mahnke, Ana, Salazar, Sandra, Elhawary, Jennifer, Huntsman, Scott, Medina, Vivian, Nickerson, Deborah A, Germer, Soren, Zody, Michael C, Abecasis, Gonçalo, Kang, Hyun Min, Rice, Kenneth M, Kumar, Rajesh, Zaitlen, Noah A, Oh, Sam, Rodríguez-Santana, José, Burchard, Esteban G, and Seibold, Max A

Subjects
Biological Sciences, Genetics, Human Genome, Cystic Fibrosis, Rare Diseases, Asthma, Lung, 2.1 Biological and endogenous factors, Respiratory, Good Health and Well Being, Child, Epithelium, Humans, Metaplasia, Mucin 5AC, Mucus, Transcriptome, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

To identify genetic determinants of airway dysfunction, we performed a transcriptome-wide association study for asthma by combining RNA-seq data from the nasal airway epithelium of 681 children, with UK Biobank genetic association data. Our airway analysis identified 95 asthma genes, 58 of which were not identified by transcriptome-wide association analyses using other asthma-relevant tissues. Among these genes were MUC5AC, an airway mucin, and FOXA3, a transcriptional driver of mucus metaplasia. Muco-ciliary epithelial cultures from genotyped donors revealed that the MUC5AC risk variant increases MUC5AC protein secretion and mucus secretory cell frequency. Airway transcriptome-wide association analyses for mucus production and chronic cough also identified MUC5AC. These cis-expression variants were associated with trans effects on expression; the MUC5AC variant was associated with upregulation of non-inflammatory mucus secretory network genes, while the FOXA3 variant was associated with upregulation of type-2 inflammation-induced mucus-metaplasia pathway genes. Our results reveal genetic mechanisms of airway mucus pathobiology.

Published
2022

4. Variant-specific inflation factors for assessing population stratification at the phenotypic variance level.

Author

Sofer, Tamar, Zheng, Xiuwen, Laurie, Cecelia A, Gogarten, Stephanie M, Brody, Jennifer A, Conomos, Matthew P, Bis, Joshua C, Thornton, Timothy A, Szpiro, Adam, O'Connell, Jeffrey R, Lange, Ethan M, Gao, Yan, Cupples, L Adrienne, Psaty, Bruce M, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, and Rice, Kenneth M

Subjects
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Humans, Sample Size, Gene Frequency, Phenotype, Algorithms, Computer Simulation, Genetic Variation, Genome-Wide Association Study
Abstract

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term 'variance stratification'. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from multiple studies. We describe a WGS-appropriate analysis approach, implemented in freely-available software, which allows study-specific variances and thereby improves performance in practice. We illustrate the variance stratification problem, its solutions, and the proposed diagnostic procedure, in simulations and in data from the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed), used in association tests for hemoglobin concentrations and BMI.

Published
2021

5. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Ärnlöv, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engström, Gunnar, Esko, Tõnu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, März, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Regeneron Genetics Center, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, and Stott, David J

Subjects
Regeneron Genetics Center, Humans, Atrial Fibrillation, Cardiomyopathies, Microfilament Proteins, Adaptor Proteins, Signal Transducing, Carrier Proteins, Muscle Proteins, Risk Factors, Case-Control Studies, Ventricular Function, Left, Cyclin-Dependent Kinase Inhibitor p21, Apoptosis Regulatory Proteins, Coronary Artery Disease, Heart Failure, Genome-Wide Association Study, Mendelian Randomization Analysis, Adaptor Proteins, Signal Transducing, Ventricular Function, Left
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Published
2020

6. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author

Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O’Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.

Published
2022
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7. Publisher Correction: Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes

Author

Halford, Jennifer L., Morrill, Valerie N., Choi, Seung Hoan, Jurgens, Sean J., Melloni, Giorgio, Marston, Nicholas A., Weng, Lu-Chen, Nauffal, Victor, Hall, Amelia W., Gunn, Sophia, Austin-Tse, Christina A., Pirruccello, James P., Khurshid, Shaan, Rehm, Heidi L., Benjamin, Emelia J., Boerwinkle, Eric, Brody, Jennifer A., Correa, Adolfo, Fornwalt, Brandon K., Gupta, Namrata, Haggerty, Christopher M., Harris, Stephanie, Heckbert, Susan R., Hong, Charles C., Kooperberg, Charles, Lin, Henry J., Loos, Ruth J. F., Mitchell, Braxton D., Morrison, Alanna C., Post, Wendy, Psaty, Bruce M., Redline, Susan, Rice, Kenneth M., Rich, Stephen S., Rotter, Jerome I., Schnatz, Peter F., Soliman, Elsayed Z., Sotoodehnia, Nona, Wong, Eugene K., Sabatine, Marc S., Ruff, Christian T., Lunetta, Kathryn L., Ellinor, Patrick T., and Lubitz, Steven A.

Published
2022
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8. Author Correction: Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology

Author

Sajuthi, Satria P., Everman, Jamie L., Jackson, Nathan D., Saef, Benjamin, Rios, Cydney L., Moore, Camille M., Mak, Angel C. Y., Eng, Celeste, Fairbanks–Mahnke, Ana, Salazar, Sandra, Elhawary, Jennifer, Huntsman, Scott, Medina, Vivian, Nickerson, Deborah A., Germer, Soren, Zody, Michael C., Abecasis, Gonçalo, Kang, Hyun Min, Rice, Kenneth M., Kumar, Rajesh, Zaitlen, Noah A., Oh, Sam, Rodríguez–Santana, José, Burchard, Esteban G., and Seibold, Max A.

Published
2022
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9. Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

Author

Sajuthi, Satria P., DeFord, Peter, Li, Yingchun, Jackson, Nathan D., Montgomery, Michael T., Everman, Jamie L., Rios, Cydney L., Pruesse, Elmar, Nolin, James D., Plender, Elizabeth G., Wechsler, Michael E., Mak, Angel C. Y., Eng, Celeste, Salazar, Sandra, Medina, Vivian, Wohlford, Eric M., Huntsman, Scott, Nickerson, Deborah A., Germer, Soren, Zody, Michael C., Abecasis, Gonçalo, Kang, Hyun Min, Rice, Kenneth M., Kumar, Rajesh, Oh, Sam, Rodriguez-Santana, Jose, Burchard, Esteban G., and Seibold, Max A.

Published
2020
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10. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Author

Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P., Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B., Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y., Bansal, Nisha, Feitosa, Mary F., Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O., van der Most, Peter J., Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan J. L., Baptista, Daniela, Biggs, Mary L., Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J., Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P., Coresh, Josef, Corre, Tanguy, Danesh, John, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F., Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Gansevoort, Ron T., Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B., Hicks, Andrew A., Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M. Arfan, Ingelsson, Erik, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Lange, Leslie A., Langefeld, Carl D., Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Maranville, Joseph C., Mascalzoni, Deborah, McMullen, Barbara, Meisinger, Christa, Meitinger, Thomas, Miliku, Kozeta, Mook-Kanamori, Dennis O., Müller-Nurasyid, Martina, Mychaleckyj, Josyf C., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Noordam, Raymond, Connell, Jeffrey O’, Olafsson, Isleifur, Palmer, Nicholette D., Peters, Annette, Podgornaia, Anna I., Ponte, Belen, Poulain, Tanja, Pramstaller, Peter P., Rabelink, Ton J., Raffield, Laura M., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rivadeneira, Fernando, Runz, Heiko, Ryan, Kathleen A., Sabanayagam, Charumathi, Saum, Kai-Uwe, Schöttker, Ben, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Strauch, Konstantin, Stumvoll, Michael, Sun, Benjamin B., Szymczak, Silke, Tai, E-Shyong, Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorsteinsdottir, Unnur, Tönjes, Anke, Tremblay, Johanne, Uitterlinden, André G., van der Harst, Pim, Verweij, Niek, Vogelezang, Suzanne, Völker, Uwe, Waldenberger, Melanie, Wang, Chaolong, Wilson, Otis D., Wong, Charlene, Wong, Tien-Yin, Yang, Qiong, Yasuda, Masayuki, Akilesh, Shreeram, Bochud, Murielle, Böger, Carsten A., Devuyst, Olivier, Edwards, Todd L., Ho, Kevin, Morris, Andrew P., Parsa, Afshin, Pendergrass, Sarah A., Psaty, Bruce M., Rotter, Jerome I., Stefansson, Kari, Wilson, James G., Susztak, Katalin, Snieder, Harold, Heid, Iris M., Scholz, Markus, Butterworth, Adam S., Hung, Adriana M., Pattaro, Cristian, and Köttgen, Anna

Published
2019
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11. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Author

Tobias Hermle, Holger Kirsten, Karsten B. Sieber, Aiko P. J. de Vries, Su Chi Lim, Peter Kovacs, Charumathi Sabanayagam, Carl D. Langefeld, Bernhard K. Krämer, Kent D. Taylor, Janine F. Felix, Belen Ponte, Markus Loeffler, Mary F. Feitosa, Kai-Uwe Eckardt, Jianjun Liu, Katalin Dittrich, Charlene A. Wong, Uwe Völker, Adriana M. Hung, Thomas Meitinger, Anubha Mahajan, Anselm Hoppmann, Erik Ingelsson, Martin H. de Borst, Oscar H. Franco, Niek Verweij, Kai-Uwe Saum, Vilmundur Gudnason, Bram P. Prins, Carsten A. Böger, Terho Lehtimäki, Andrew A. Hicks, Todd L. Edwards, Olivier Devuyst, Peter P. Pramstaller, Katrin Horn, Leslie A. Lange, Johanne Tremblay, Jin-Fang Chai, Sahar Ghasemi, Kjell Nikus, Tanja Poulain, Massimiliano Cocca, Anna Köttgen, Eric Boerwinkle, Barry I. Freedman, Miao-Ling Chee, Man Li, Stephan J. L. Bakker, Tamara B. Harris, Albert V. Smith, Ton J. Rabelink, Dennis O. Mook-Kanamori, Iris M. Heid, Jasmin Divers, Chaolong Wang, Kathleen A. Ryan, Pavel Hamet, Silke Szymczak, Shih-Jen Hwang, Hauke Thomsen, Rainer Rettig, Ayush Giri, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Cristian Pattaro, Andrej Teren, Valencia Hui Xian Foo, Myriam Rheinberger, Audrey Y. Chu, Barbara McMullen, Franziska Grundner-Culemann, Masayuki Yasuda, Murielle Bochud, Martin Gögele, Anke Tönjes, Jeannette Lee, Adrienne Tin, Kevin Ho, Konstantin Strauch, Josef Coresh, Renée de Mutsert, Sandra Freitag-Wolf, Gardar Sveinbjornsson, Yizhe Xu, Katalin Susztak, Tien Yin Wong, Mary L. Biggs, Isleifur Olafsson, Qiong Yang, Antje Körner, Chengxiang Qiu, E-Shyong Tai, Martina Müller-Nurasyid, Ben Schöttker, Jeffrey O' Connell, Mengmeng Chen, Daniel F. Gudbjartsson, Dermot F. Reilly, Vincent W. V. Jaddoe, Damia Noce, Pim van der Harst, Sanaz Sedaghat, Chiea Chuen Khor, Adam S. Butterworth, Mathias Gorski, Robert J. Carroll, James G. Wilson, Johan Ärnlöv, Christa Meisinger, Kenneth Rice, Bettina Jung, Christian M. Shaffer, Unnur Thorsteinsdottir, Matthias Nauck, Shreeram Akilesh, Mika Kähönen, Johanna Jakobsdottir, Melanie Waldenberger, Ralph Burkhardt, Daniela Baptista, John Danesh, Benjamin B. Sun, Karlhans Endlich, Holly Kramer, Frauke Degenhardt, Wolfgang Lieb, Kari Stefansson, Joachim Thiery, Lars Lind, Nicholette D. Palmer, Sarah A. Pendergrass, Suzanne Vogelezang, Peter J. van der Most, Afshin Parsa, Markus Scholz, Florian Kronenberg, Joseph C. Maranville, Laura M. Raffield, Hermann Brenner, Wieland Kiess, Anna I. Podgornaia, Yuan Shi, Tanguy Corre, Miao-Li Chee, Deborah Mascalzoni, Bamidele O. Tayo, Navya Shilpa Josyula, Ching-Yu Cheng, Lea Gerstner, Nisha Bansal, Jerome I. Rotter, Alexander Teumer, Vilmantas Giedraitis, Raymond Noordam, Ron T. Gansevoort, Lihua Wang, Andrew P. Morris, Bruce M. Psaty, Boting Ning, Zhi Yu, Christian Fuchsberger, Matthias Wuttke, Heiko Runz, Annette Peters, Yih Chung Tham, James P. Cook, Yong Li, Chris H. L. Thio, Hilma Holm, Alessandro De Grandi, Jonathan Marten, André G. Uitterlinden, Andre Franke, Nicholas Y. Q. Tan, Otis D. Wilson, Georg Ehret, Cecilia M. Lindgren, Josyf C. Mychaleckyj, Wolfgang Koenig, Harold Snieder, Michael Stumvoll, Kozeta Miliku, M. Arfan Ikram, Teresa Nutile, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands, University of Iceland, Teumer, Alexander [0000-0002-8309-094X], Li, Yong [0000-0003-2651-8791], Wuttke, Matthias [0000-0003-3420-5082], Giri, Ayush [0000-0002-7786-4670], Qiu, Chengxiang [0000-0002-6346-8669], Kirsten, Holger [0000-0002-3126-7950], Tin, Adrienne [0000-0002-4207-5866], Feitosa, Mary F. [0000-0002-0933-2410], Chai, Jin-Fang [0000-0003-3770-1137], Cocca, Massimiliano [0000-0002-1127-7596], Gorski, Mathias [0000-0002-9103-5860], Horn, Katrin [0000-0002-5307-6936], Li, Man [0000-0002-3839-0281], Marten, Jonathan [0000-0001-6916-2014], van der Most, Peter J. 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[0000-0002-4903-9374], Liu, Jianjun [0000-0002-3255-3019], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Mahajan, Anubha [0000-0001-5585-3420], Mascalzoni, Deborah [0000-0003-4156-1464], Miliku, Kozeta [0000-0002-9614-7191], Müller-Nurasyid, Martina [0000-0003-3793-5910], Mychaleckyj, Josyf C. [0000-0003-2595-0005], Palmer, Nicholette D. [0000-0001-8883-2511], Poulain, Tanja [0000-0003-3825-5829], Raffield, Laura M. [0000-0002-7892-193X], Rice, Kenneth M. [0000-0002-3071-7278], Rivadeneira, Fernando [0000-0001-9435-9441], Sabanayagam, Charumathi [0000-0002-4042-4719], Smith, Albert V. [0000-0003-1942-5845], Sun, Benjamin B. [0000-0001-6347-2281], Szymczak, Silke [0000-0002-8897-9035], Taylor, Kent D. [0000-0002-2756-4370], Thio, Chris H. L. [0000-0003-2623-7172], Uitterlinden, André G. [0000-0002-7276-3387], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Völker, Uwe [0000-0002-5689-3448], Wang, Chaolong [0000-0003-3945-1012], Yang, Qiong [0000-0002-3658-1375], Devuyst, Olivier [0000-0003-3744-4767], Edwards, Todd L. [0000-0003-4318-6119], Ho, Kevin [0000-0002-3054-8697], Morris, Andrew P. [0000-0002-6805-6014], Pendergrass, Sarah A. [0000-0002-0565-6522], Rotter, Jerome I. [0000-0001-7191-1723], Stefansson, Kari [0000-0003-1676-864X], Susztak, Katalin [0000-0002-1005-3726], Scholz, Markus [0000-0002-4059-1779], Butterworth, Adam S. [0000-0002-6915-9015], Hung, Adriana M. [0000-0002-3203-1608], Pattaro, Cristian [0000-0002-4119-0109], Köttgen, Anna [0000-0002-4671-3714], Apollo - University of Cambridge Repository, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Feitosa, Mary F [0000-0002-0933-2410], van der Most, Peter J [0000-0001-8450-3518], de Borst, Martin H [0000-0002-4127-8733], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Hicks, Andrew A [0000-0001-6320-0411], Ikram, M Arfan [0000-0003-0372-8585], Jaddoe, Vincent WV [0000-0003-2939-0041], Lindgren, Cecilia M [0000-0002-4903-9374], Mychaleckyj, Josyf C [0000-0003-2595-0005], Palmer, Nicholette D [0000-0001-8883-2511], Raffield, Laura M [0000-0002-7892-193X], Rice, Kenneth M [0000-0002-3071-7278], Smith, Albert V [0000-0003-1942-5845], Sun, Benjamin B [0000-0001-6347-2281], Taylor, Kent D [0000-0002-2756-4370], Thio, Chris HL [0000-0003-2623-7172], Uitterlinden, André G [0000-0002-7276-3387], Edwards, Todd L [0000-0003-4318-6119], Morris, Andrew P [0000-0002-6805-6014], Pendergrass, Sarah A [0000-0002-0565-6522], Rotter, Jerome I [0000-0001-7191-1723], Butterworth, Adam S [0000-0002-6915-9015], and Hung, Adriana M [0000-0002-3203-1608]

Subjects
0301 basic medicine, Drosophila melanogaster/genetics, Diabetes Mellitus/genetics, LD SCORE REGRESSION, 030232 urology & nephrology, 45/43, General Physics and Astronomy, Genome-wide association study, BLOOD-PRESSURE, Bioinformatics, GLOMERULAR-FILTRATION-RATE, Genome-wide association studies, Diabetes mellitus genetics, 0302 clinical medicine, Creatinine/urine, Risk Factors, Genome-wide, Phenomics, lcsh:Science, ddc:616, Regulation of gene expression, RISK, Gene knockdown, Kidney diseases, Multidisciplinary, HERITABILITY, Albuminuria/genetics, article, Chromosome Mapping, Kidney disease, ddc, 3. Good health, Drosophila melanogaster, Creatinine, Nýrnasjúkdómar, 692/4022/1585, Slit diaphragm, Medical genetics, medicine.symptom, Erfðarannsóknir, Medical Genetics, medicine.medical_specialty, Science, 631/208/205/2138, 610 Medicine & health, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Meta-Analysis as Topic, 360 Social problems & social services, Diabetes Mellitus, medicine, Animals, Humans, Albuminuria, Genetic Predisposition to Disease, ddc:610, EXCRETION RATE, CARDIOVASCULAR EVENTS, Genetic association, Medicinsk genetik, TRANS-EQTLS, KIDNEY-DISEASE, General Chemistry, 030104 developmental biology, Gene Expression Regulation, Genetic Loci, COLLABORATIVE METAANALYSIS, lcsh:Q, Genome-Wide Association Study
Abstract

Publisher's version (útgefin grein)., Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria., Competing interests: Karsten B. Sieber is full-time employee of GlaxoSmithKline. Gardar Sveinbjornsson, Daniel F. Gudbjartsson, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are full-time employees of deCODE genetics, Amgen Inc. John Danesh is member of the Novartis Cardiovascular and Metabolic Advisory Board, received grant support from Novartis. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Wolfgang Koenig received modest consultation fees for advisory board meetings from Amgen, DalCor, Kowa, Novartis, Pfizer and Sanofi, and modest personal fees for lectures from Amgen, AstraZeneca, Novartis, Pfizer and Sanofi. Anna I. Podgornaia and Dermot F. Reilly are employees of Merck Sharp Dohme Corp., Whitehouse Station, NJ, USA. Kevin Ho disclosed a research and financial relationship with Sanofi-Genzyme. Bruce M. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Markus Scholz: Consultancy of and grant support from Merck Serono not related to this project. Adam S. Butterworth received grants from MSD, Pfizer, Novartis, Biogen and Bioverativ and personal fees from Novartis. Anna Köttgen received grant support from Gruenenthal not related to this project. The other authors declare no competing interests.

Published
2019
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