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11 results on '"Guettouche, Toumy"'

1. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Author

Weiner, January, Suwalski, Phillip, Holtgrewe, Manuel, Rakitko, Alexander, Thibeault, Charlotte, Müller, Melina, Patriki, Dimitri, Quedenau, Claudia, Krüger, Ulrike, Ilinsky, Valery, Popov, Iaroslav, Balnis, Joseph, Jaitovich, Ariel, Helbig, Elisa T, Lippert, Lena J, Stubbemann, Paula, Real, Luis M, Macías, Juan, Pineda, Juan A, Fernandez-Fuertes, Marta, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Salvo, Mauricio, Blueher, Anja, Siemann, Sandra, Jurisic, Stjepan, Beer, Juerg H, Rutishauser, Jonas, Wiggli, Benedikt, Schmid, Hansruedi, Danninger, Kathrin, Binder, Ronald, Corman, Victor M, Mühlemann, Barbara, Arkal, Rao Arjun, Fragiadakis, Gabriela K, Mick, Eran, COMET, Consortium, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn M, Kangelaris, Kirsten N, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Venkataramani, Urmila, García, Federico, Zyla, Joanna, Drosten, Christian, Alice, Braun, Jones, Terry C, Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Zemojtel, Tomasz, Skurk, Carsten, Poller, Wolfgang, Borodina, Tatiana, Pa-COVID, Study Group, Ripke, Stephan, Sander, Leif E, Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, and Heidecker, Bettina

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Coronaviruses, Emerging Infectious Diseases, Human Genome, Clinical Research, Infectious Diseases, Genetics, 2.1 Biological and endogenous factors, 2.5 Research design and methodologies (aetiology), Good Health and Well Being, SARS-CoV-2, COVID-19, Human Leukocyte Antigen&nbsp, intubation, Human Leukocyte Antigen, Clinical sciences, Health services and systems, Public health
Abstract

BackgroundSince the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing.MethodsWe analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS).FindingsWe describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles.InterpretationHLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2.FundingFunded by Roche Sequencing Solutions, Inc.

Published
2021

2. Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19

Author

Dannebaum, Richard, Suwalski, Phillip, Asgharian, Hosseinali, Du Zhipei, Gracie, Lin, Hai, Weiner, January, 3rd, Holtgrewe, Manuel, Thibeault, Charlotte, Müller, Melina, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Blüher, Anja, Siemann, Sandra, Telman, Dilduz, Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Skurk, Carsten, Poller, Wolfgang, Sander, Leif E, Beule, Dieter, Kurth, Florian, Guettouche, Toumy, Landmesser, Ulf, Berka, Jan, Luong, Khai, Rubelt, Florian, and Heidecker, Bettina

Published
2022
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3. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Author

Weiner, January, 3rd, Suwalski, Phillip, Holtgrewe, Manuel, Rakitko, Alexander, Thibeault, Charlotte, Müller, Melina, Patriki, Dimitri, Quedenau, Claudia, Krüger, Ulrike, Ilinsky, Valery, Popov, Iaroslav, Balnis, Joseph, Jaitovich, Ariel, Helbig, Elisa T, Lippert, Lena J, Stubbemann, Paula, Real, Luis M, Macías, Juan, Pineda, Juan A, Fernandez-Fuertes, Marta, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Salvo, Mauricio, Blueher, Anja, Siemann, Sandra, Jurisic, Stjepan, Beer, Juerg H., Rutishauser, Jonas, Wiggli, Benedikt, Schmid, Hansruedi, Danninger, Kathrin, Binder, Ronald, Corman, Victor M, Mühlemann, Barbara, Arjun Arkal, Rao, Fragiadakis, Gabriela K., Mick, Eran, COMET, Consortium, Calfee, Carolyn S., Erle, David J., Hendrickson, Carolyn M., Kangelaris, Kirsten N., Krummel, Matthew F., Woodruff, Prescott G., Langelier, Charles R., Venkataramani, Urmila, García, Federico, Zyla, Joanna, Drosten, Christian, Alice, Braun, Jones, Terry C, Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Zemojtel, Tomasz, Skurk, Carsten, Poller, Wolfgang, Borodina, Tatiana, Pa-COVID, Study Group, Ripke, Stephan, Sander, Leif E, Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, and Heidecker, Bettina

Published
2021
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4. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies.

Author

Li, Yun, van Setten, Jessica, Verma, Shefali, Lu, Yontao, Holmes, Michael, Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad, Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael, Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey, McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain, Al-Ali, Amein, Al-Muhanna, Fahad, Al-Rubaish, Abdullah, Al-Mueilo, Samir, Monos, Dimitri, Murphy, Barbara, Olthoff, Kim, Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew, Oetting, William, Garcia-Pavia, Pablo, MacArthur, Daniel, de Bakker, Paul, Hakonarson, Hakon, Birdwell, Kelly, Jacobson, Pamala, Ritchie, Marylyn, Asselbergs, Folkert, Israni, Ajay, Shaked, Abraham, and Keating, Brendan

Subjects
DNA Copy Number Variations, Genome-Wide Association Study, Genotype, HLA Antigens, Humans, Polymorphism, Single Nucleotide, Receptors, KIR
Abstract

BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. METHODS: We describe here the design and implementation of a customized genome-wide genotyping array, the TxArray, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Published
2015

5. MALE SEX, HLA-C*04:01 AND COVID-19: A RISKY CONSTELLATION

Author

Suwalski, Phillip, primary, Patriki, Dimitri, additional, Quedenau, Claudia, additional, Borodina, Tatiana, additional, Beer, Juerg H., additional, Wiggli, Benedikt, additional, Guettouche, Toumy, additional, Landmesser, Ulf, additional, and Heidecker, Bettina, additional

Published
2022
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6. Design and Implementation of the International Genetics and Translational Research in Transplantation Network

Author

Keating, Brendan J., van Setten, Jessica, Jacobson, Pamala A., Holmes, Michael V., Verma, Shefali S., Chandrupatla, Hareesh R., Nair, Nikhil, Gao, Hui, Li, Yun R., Chang, Bao-Li, Wong, Chanel, Phillips, Randy, Cole, Brian S., Mukhtar, Eyas, Zhang, Weijia, Cao, Hongzhi, Mohebnasab, Maede, Hou, Cuiping, Lee, Takesha, Steel, Laura, Shaked, Oren, Garifallou, James, Miller, Michael B., Karczewski, Konrad J., Akdere, Abdullah, Gonzalez, Ana, Lloyd, Kelsey M., McGinn, Daniel, Michaud, Zach, Colasacco, Abigail, Lek, Monkol, Fu, Yao, Pawashe, Mayur, Guettouche, Toumy, Himes, Aubree, Perez, Leat, Guan, Weihua, Wu, Baolin, Schladt, David, Menon, Madhav, Zhang, Zhongyang, Tragante, Vinicius, de Jonge, Nicolaas, Otten, Henny G., de Weger, Roel A., van de Graaf, Ed A., Baan, Carla C., Manintveld, Olivier C., De Vlaminck, Iwijn, Piening, Brian D., Strehl, Calvin, Shaw, Mary, Snieder, Harold, Klintmalm, Goran B., O'Leary, Jacqueline G., Amaral, Sandra, Goldfarb, Samuel, Rand, Elizabeth, Rossano, Joseph W., Kohli, Utkarsh, Heeger, Peter, Stahl, Eli, Christie, Jason D., Fuentes, Maria Hernandez, Levine, John E., Aplenc, Richard, Schadt, Eric E., Stranger, Barbara E., Kluin, Jolanda, Potena, Luciano, Zuckermann, Andreas, Khush, Kiran, Alzahrani, Alhusain J., Al-Muhanna, Fahad A., Al-Ali, Amein K., Al-Ali, Rudaynah, Al-Rubaish, Abdullah M., Al-Mueilo, Samir, Byrne, Edna M., Miller, David, Alexander, Stephen I., Onengut-Gumuscu, Suna, Rich, Stephen S., Suthanthiran, Manikkam, Tedesco, Helio, Saw, Chee L., Ragoussis, Jiannis, Kfoury, Abdallah G., Horne, Benjamin, Carlquist, John, Gerstein, Mark B., Reindl-Schwaighofer, Roman, Oberbauer, Rainer, Wijmenga, Cisca, Palmer, Scott, Pereira, Alexandre C., Segovia, Javier, Alonso-Pulpon, Luis A., Comez-Bueno, Manuel, Vilches, Carlos, Jaramillo, Natalia, de Borst, Martin H., Naesens, Maarten, Hao, Ke, MacArthur, DanielG., Balasubramanian, Suganthi, Conlon, Peter J., Lord, Graham M., Ritchie, Marylyn D., Snyder, Michael, Olthoff, Kim M., Moore, Jason H., Petersdorf, Effie W., Kamoun, Malek, Wang, Jun, Monos, Dimitri S., de Bakker, Paul I. W., Hakonarson, Hakon, Murphy, Barbara, Lankree, Matthew B., Garcia-Pavia, Pablo, Oetting, William S., Birdwell, Kelly A., Bakker, Stephan J. L., Israni, Ajay K., Shaked, Abraham, Asselbergs, Folkert W., Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Kidney Center (GKC), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT), Gastroenterology & Hepatology, Dermatology, Erasmus MC other, Internal Medicine, Cardiology, and Cardiothoracic Surgery

Subjects
Graft Rejection, International Cooperation, Genome-wide association study, 030230 surgery, VARIANTS, Organ transplantation, Organizational, Translational Research, Biomedical, 0302 clinical medicine, Models, Risk Factors, Databases, Genetic, Medicine, CARDIAC TRANSPLANTATION, Cooperative Behavior, Non-U.S. Gov't, Translational Medical Research, Genetics, 0303 health sciences, Research Support, Non-U.S. Gov't, Graft Survival, Single Nucleotide, Original Clinical Science—General, 3. Good health, GENOTYPE, surgical procedures, operative, Phenotype, Treatment Outcome, Research Design, Genetic Markers, medicine.medical_specialty, Primary Graft Dysfunction, Translational research, Human leukocyte antigen, Research Support, DONOR, Polymorphism, Single Nucleotide, N.I.H, 03 medical and health sciences, Databases, Genetic, SDG 3 - Good Health and Well-being, Research Support, N.I.H., Extramural, Journal Article, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, PRIMARY GRAFT DYSFUNCTION, Genetic Association Studies, 030304 developmental biology, Genetic association, Transplantation, business.industry, ELECTRONIC MEDICAL-RECORDS, Extramural, Organ Transplantation, Genetic architecture, POLYMORPHISM, RECIPIENTS, Models, Organizational, Sample Size, KIDNEY ALLOGRAFT FUNCTION, business
Abstract

Background Genetic association studies of transplantation outcomes have been hampered by small samples and highly complex multifactorial phenotypes, hindering investigations of the genetic architecture of a range of comorbidities which significantly impact graft and recipient life expectancy. We describe here the rationale and design of the International Genetics & Translational Research in Transplantation Network. The network comprises 22 studies to date, including 16494 transplant recipients and 11669 donors, of whom more than 5000 are of non-European ancestry, all of whom have existing genomewide genotype data sets. Methods We describe the rich genetic and phenotypic information available in this consortium comprising heart, kidney, liver, and lung transplant cohorts. Results We demonstrate significant power in International Genetics & Translational Research in Transplantation Network to detect main effect association signals across regions such as the MHC region as well as genomewide for transplant outcomes that span all solid organs, such as graft survival, acute rejection, new onset of diabetes after transplantation, and for delayed graft function in kidney only. Conclusions This consortium is designed and statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The study design allows a spectrum of analyses to be performed including recipient-only analyses, donor-recipient HLA mismatches with focus on loss-of-function variants and nonsynonymous single nucleotide polymorphisms., iGeneTRAiN is a consortium that has genome-wide genotype datasets. These genomic data allows robust statistically analysis of genetic associations that impact graft and patients variables such as, such as: graft survival, acute rejection, new onset of diabetes after transplantation, and delayed graft kidney function. Supplemental digital content is available in the text.

Published
2015

7. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

Author

Li, Yun R., van Setten, Jessica, Verma, Shefali S., Lu, Yontao, Holmes, Michael V., Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad J., Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael B., Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey M., McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain J., Al-Ali, Amein K., Al-Muhanna, Fahad A., Al-Rubaish, Abdullah M., Al-Mueilo, Samir, Monos, Dimitri S., Murphy, Barbara, Olthoff, Kim M., Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew B., Oetting, William S., Garcia-Pavia, Pablo, MacArthur, Daniel G., de Bakker, Paul I W, Hakonarson, Hakon, Birdwell, Kelly A., Jacobson, Pamala A., Ritchie, Marylyn D., Asselbergs, Folkert W., Israni, Ajay K., Shaked, Abraham, Keating, Brendan J., Li, Yun R., van Setten, Jessica, Verma, Shefali S., Lu, Yontao, Holmes, Michael V., Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad J., Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael B., Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey M., McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain J., Al-Ali, Amein K., Al-Muhanna, Fahad A., Al-Rubaish, Abdullah M., Al-Mueilo, Samir, Monos, Dimitri S., Murphy, Barbara, Olthoff, Kim M., Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew B., Oetting, William S., Garcia-Pavia, Pablo, MacArthur, Daniel G., de Bakker, Paul I W, Hakonarson, Hakon, Birdwell, Kelly A., Jacobson, Pamala A., Ritchie, Marylyn D., Asselbergs, Folkert W., Israni, Ajay K., Shaked, Abraham, and Keating, Brendan J.

Published
2015

8. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies.

Author

Li, Yun R, van Setten, Jessica, Verma, Shefali S, Lu, Yontao, Holmes, Michael V, Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad J, Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael B, Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey M, McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain J, Al-Ali, Amein K, Al-Muhanna, Fahad A, Al-Rubaish, Abdullah M, Al-Mueilo, Samir, Monos, Dimitri S, Murphy, Barbara, Olthoff, Kim M, Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew B, Oetting, William S, Garcia-Pavia, Pablo, MacArthur, Daniel G, de Bakker, Paul IW, Hakonarson, Hakon, Birdwell, Kelly A, Jacobson, Pamala A, Ritchie, Marylyn D, Asselbergs, Folkert W, Israni, Ajay K, Shaked, Abraham, Keating, Brendan J, Li, Yun R, van Setten, Jessica, Verma, Shefali S, Lu, Yontao, Holmes, Michael V, Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad J, Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael B, Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey M, McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain J, Al-Ali, Amein K, Al-Muhanna, Fahad A, Al-Rubaish, Abdullah M, Al-Mueilo, Samir, Monos, Dimitri S, Murphy, Barbara, Olthoff, Kim M, Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew B, Oetting, William S, Garcia-Pavia, Pablo, MacArthur, Daniel G, de Bakker, Paul IW, Hakonarson, Hakon, Birdwell, Kelly A, Jacobson, Pamala A, Ritchie, Marylyn D, Asselbergs, Folkert W, Israni, Ajay K, Shaked, Abraham, and Keating, Brendan J

Abstract

BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. METHODS: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Published
2015

9. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

Author

Experimentele Afd. Cardiologie 1, Circulatory Health, Infection & Immunity, JC onderzoeksprogramma Methodologie, Cancer, Cardiologie, Li, Yun R., van Setten, Jessica, Verma, Shefali S., Lu, Yontao, Holmes, Michael V., Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad J., Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael B., Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey M., McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain J., Al-Ali, Amein K., Al-Muhanna, Fahad A., Al-Rubaish, Abdullah M., Al-Mueilo, Samir, Monos, Dimitri S., Murphy, Barbara, Olthoff, Kim M., Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew B., Oetting, William S., Garcia-Pavia, Pablo, MacArthur, Daniel G., de Bakker, Paul I W, Hakonarson, Hakon, Birdwell, Kelly A., Jacobson, Pamala A., Ritchie, Marylyn D., Asselbergs, Folkert W., Israni, Ajay K., Shaked, Abraham, Keating, Brendan J., Experimentele Afd. Cardiologie 1, Circulatory Health, Infection & Immunity, JC onderzoeksprogramma Methodologie, Cancer, Cardiologie, Li, Yun R., van Setten, Jessica, Verma, Shefali S., Lu, Yontao, Holmes, Michael V., Gao, Hui, Lek, Monkol, Nair, Nikhil, Chandrupatla, Hareesh, Chang, Baoli, Karczewski, Konrad J., Wong, Chanel, Mohebnasab, Maede, Mukhtar, Eyas, Phillips, Randy, Tragante, Vinicius, Hou, Cuiping, Steel, Laura, Lee, Takesha, Garifallou, James, Guettouche, Toumy, Cao, Hongzhi, Guan, Weihua, Himes, Aubree, van Houten, Jacob, Pasquier, Andrew, Yu, Reina, Carrigan, Elena, Miller, Michael B., Schladt, David, Akdere, Abdullah, Gonzalez, Ana, Llyod, Kelsey M., McGinn, Daniel, Gangasani, Abhinav, Michaud, Zach, Colasacco, Abigail, Snyder, James, Thomas, Kelly, Wang, Tiancheng, Wu, Baolin, Alzahrani, Alhusain J., Al-Ali, Amein K., Al-Muhanna, Fahad A., Al-Rubaish, Abdullah M., Al-Mueilo, Samir, Monos, Dimitri S., Murphy, Barbara, Olthoff, Kim M., Wijmenga, Cisca, Webster, Teresa, Kamoun, Malek, Balasubramanian, Suganthi, Lanktree, Matthew B., Oetting, William S., Garcia-Pavia, Pablo, MacArthur, Daniel G., de Bakker, Paul I W, Hakonarson, Hakon, Birdwell, Kelly A., Jacobson, Pamala A., Ritchie, Marylyn D., Asselbergs, Folkert W., Israni, Ajay K., Shaked, Abraham, and Keating, Brendan J.

Published
2015

10. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

Author

Li, Yun R., primary, van Setten, Jessica, additional, Verma, Shefali S., additional, Lu, Yontao, additional, Holmes, Michael V., additional, Gao, Hui, additional, Lek, Monkol, additional, Nair, Nikhil, additional, Chandrupatla, Hareesh, additional, Chang, Baoli, additional, Karczewski, Konrad J., additional, Wong, Chanel, additional, Mohebnasab, Maede, additional, Mukhtar, Eyas, additional, Phillips, Randy, additional, Tragante, Vinicius, additional, Hou, Cuiping, additional, Steel, Laura, additional, Lee, Takesha, additional, Garifallou, James, additional, Guettouche, Toumy, additional, Cao, Hongzhi, additional, Guan, Weihua, additional, Himes, Aubree, additional, van Houten, Jacob, additional, Pasquier, Andrew, additional, Yu, Reina, additional, Carrigan, Elena, additional, Miller, Michael B., additional, Schladt, David, additional, Akdere, Abdullah, additional, Gonzalez, Ana, additional, Llyod, Kelsey M., additional, McGinn, Daniel, additional, Gangasani, Abhinav, additional, Michaud, Zach, additional, Colasacco, Abigail, additional, Snyder, James, additional, Thomas, Kelly, additional, Wang, Tiancheng, additional, Wu, Baolin, additional, Alzahrani, Alhusain J., additional, Al-Ali, Amein K., additional, Al-Muhanna, Fahad A., additional, Al-Rubaish, Abdullah M., additional, Al-Mueilo, Samir, additional, Monos, Dimitri S., additional, Murphy, Barbara, additional, Olthoff, Kim M., additional, Wijmenga, Cisca, additional, Webster, Teresa, additional, Kamoun, Malek, additional, Balasubramanian, Suganthi, additional, Lanktree, Matthew B., additional, Oetting, William S., additional, Garcia-Pavia, Pablo, additional, MacArthur, Daniel G., additional, de Bakker, Paul I W, additional, Hakonarson, Hakon, additional, Birdwell, Kelly A., additional, Jacobson, Pamala A., additional, Ritchie, Marylyn D., additional, Asselbergs, Folkert W., additional, Israni, Ajay K., additional, Shaked, Abraham, additional, and Keating, Brendan J., additional

Published
2015
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