Search

Your search keyword '"Bruce Gelb"' showing total 24 results
Start Over Author "Bruce Gelb"
24 results on '"Bruce Gelb"'

3. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthmaResearch in context

Author

Kathryn Recto, Priyadarshini Kachroo, Tianxiao Huan, David Van Den Berg, Gha Young Lee, Helena Bui, Dong Heon Lee, Jessica Gereige, Chen Yao, Shih-Jen Hwang, Roby Joehanes, Scott T. Weiss, George T. O’Connor, Daniel Levy, Dawn L. DeMeo, Namiko Abe, Gonçalo Abecasis, Francois Aguet, Christine Albert, Laura Almasy, Alvaro Alonso, Seth Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum-Bowden, Kristin Ardlie, Dan Arking, Donna K. Arnett, Allison Ashley-Koch, Stella Aslibekyan, Tim Assimes, Paul Auer, Dimitrios Avramopoulos, Najib Ayas, Adithya Balasubramanian, John Barnard, Kathleen Barnes, R. Graham Barr, Emily Barron-Casella, Lucas Barwick, Terri Beaty, Gerald Beck, Diane Becker, Lewis Becker, Rebecca Beer, Amber Beitelshees, Emelia Benjamin, Takis Benos, Marcos Bezerra, Larry Bielak, Joshua Bis, Thomas Blackwell, John Blangero, Nathan Blue, Eric Boerwinkle, Donald W. Bowden, Russell Bowler, Jennifer Brody, Ulrich Broeckel, Jai Broome, Deborah Brown, Karen Bunting, Esteban Burchard, Carlos Bustamante, Erin Buth, Brian Cade, Jonathan Cardwell, Vincent Carey, Julie Carrier, April P. Carson, Cara Carty, Richard Casaburi, Juan P. Casas Romero, James Casella, Peter Castaldi, Mark Chaffin, Christy Chang, Yi-Cheng Chang, Daniel Chasman, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Yii-Der Ida Chen, Michael Cho, Seung Hoan Choi, Lee-Ming Chuang, Mina Chung, Ren-Hua Chung, Clary Clish, Suzy Comhair, Matthew Conomos, Elaine Cornell, Adolfo Correa, Carolyn Crandall, James Crapo, L. Adrienne Cupples, Joanne Curran, Jeffrey Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sean David, Colleen Davis, Michelle Daya, Mariza de Andrade, Lisa de las Fuentes, Paul de Vries, Michael DeBaun, Ranjan Deka, Dawn DeMeo, Scott Devine, Huyen Dinh, Harsha Doddapaneni, Qing Duan, Shannon Dugan-Perez, Ravi Duggirala, Jon Peter Durda, Susan K. Dutcher, Charles Eaton, Lynette Ekunwe, Adel El Boueiz, Patrick Ellinor, Leslie Emery, Serpil Erzurum, Charles Farber, Jesse Farek, Tasha Fingerlin, Matthew Flickinger, Myriam Fornage, Nora Franceschini, Chris Frazar, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Stacey Gabriel, Weiniu Gan, Shanshan Gao, Yan Gao, Margery Gass, Heather Geiger, Bruce Gelb, Mark Geraci, Soren Germer, Robert Gerszten, Auyon Ghosh, Richard Gibbs, Chris Gignoux, Mark Gladwin, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, Sharon Graw, Kathryn J. Gray, Daniel Grine, Colin Gross, C. Charles Gu, Yue Guan, Xiuqing Guo, Namrata Gupta, Jeff Haessler, Michael Hall, Yi Han, Patrick Hanly, Daniel Harris, Nicola L. Hawley, Jiang He, Ben Heavner, Susan Heckbert, Ryan Hernandez, David Herrington, Craig Hersh, Bertha Hidalgo, James Hixson, Brian Hobbs, John Hokanson, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Jianhong Hu, Yi-Jen Hung, Haley Huston, Chii Min Hwu, Marguerite Ryan Irvin, Rebecca Jackson, Deepti Jain, Cashell Jaquish, Jill Johnsen, Andrew Johnson, Craig Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert Kaplan, Sharon Kardia, Shannon Kelly, Eimear Kenny, Michael Kessler, Alyna Khan, Ziad Khan, Wonji Kim, John Kimoff, Greg Kinney, Barbara Konkle, Charles Kooperberg, Holly Kramer, Christoph Lange, Ethan Lange, Leslie Lange, Cathy Laurie, Cecelia Laurie, Meryl LeBoff, Jiwon Lee, Sandra Lee, Wen-Jane Lee, Jonathon LeFaive, David Levine, Joshua Lewis, Xiaohui Li, Yun Li, Henry Lin, Honghuang Lin, Xihong Lin, Simin Liu, Yongmei Liu, Yu Liu, Ruth J.F. Loos, Steven Lubitz, Kathryn Lunetta, James Luo, Ulysses Magalang, Michael Mahaney, Barry Make, Ani Manichaikul, Alisa Manning, JoAnn Manson, Lisa Martin, Melissa Marton, Susan Mathai, Rasika Mathias, Susanne May, Patrick McArdle, Merry-Lynn McDonald, Sean McFarland, Stephen McGarvey, Daniel McGoldrick, Caitlin McHugh, Becky McNeil, Hao Mei, James Meigs, Vipin Menon, Luisa Mestroni, Ginger Metcalf, Deborah A. Meyers, Emmanuel Mignot, Julie Mikulla, Nancy Min, Mollie Minear, Ryan L. Minster, Braxton D. Mitchell, Matt Moll, Zeineen Momin, May E. Montasser, Courtney Montgomery, Donna Muzny, Josyf C. Mychaleckyj, Girish Nadkarni, Rakhi Naik, Take Naseri, Pradeep Natarajan, Sergei Nekhai, Sarah C. Nelson, Bonnie Neltner, Caitlin Nessner, Deborah Nickerson, Osuji Nkechinyere, Kari North, Jeff O'Connell, Tim O'Connor, Heather Ochs-Balcom, Geoffrey Okwuonu, Allan Pack, David T. Paik, Nicholette Palmer, James Pankow, George Papanicolaou, Cora Parker, Gina Peloso, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Patricia Peyser, Lawrence S. Phillips, Jacob Pleiness, Toni Pollin, Wendy Post, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuss, Bruce Psaty, Pankaj Qasba, Dandi Qiao, Zhaohui Qin, Nicholas Rafaels, Laura Raffield, Mahitha Rajendran, Vasan S. Ramachandran, D.C. Rao, Laura Rasmussen-Torvik, Aakrosh Ratan, Susan Redline, Robert Reed, Catherine Reeves, Elizabeth Regan, Alex Reiner, Muagututi‘a Sefuiva Reupena, Ken Rice, Stephen Rich, Rebecca Robillard, Nicolas Robine, Dan Roden, Carolina Roselli, Jerome Rotter, Ingo Ruczinski, Alexi Runnels, Pamela Russell, Sarah Ruuska, Kathleen Ryan, Ester Cerdeira Sabino, Danish Saleheen, Shabnam Salimi, Sejal Salvi, Steven Salzberg, Kevin Sandow, Vijay G. Sankaran, Jireh Santibanez, Karen Schwander, David Schwartz, Frank Sciurba, Christine Seidman, Jonathan Seidman, Frédéric Sériès, Vivien Sheehan, Stephanie L. Sherman, Amol Shetty, Aniket Shetty, Wayne Hui-Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin Silverman, Robert Skomro, Albert Vernon Smith, Jennifer Smith, Josh Smith, Nicholas Smith, Tanja Smith, Sylvia Smoller, Beverly Snively, Michael Snyder, Tamar Sofer, Nona Sotoodehnia, Adrienne M. Stilp, Garrett Storm, Elizabeth Streeten, Jessica Lasky Su, Yun Ju Sung, Jody Sylvia, Adam Szpiro, Daniel Taliun, Hua Tang, Margaret Taub, Kent Taylor, Matthew Taylor, Simeon Taylor, Marilyn Telen, Timothy A. Thornton, Machiko Threlkeld, Lesley Tinker, David Tirschwell, Sarah Tishkoff, Hemant Tiwari, Catherine Tong, Russell Tracy, Michael Tsai, Dhananjay Vaidya, Peter VandeHaar, Scott Vrieze, Tarik Walker, Robert Wallace, Avram Walts, Fei Fei Wang, Heming Wang, Jiongming Wang, Karol Watson, Jennifer Watt, Daniel E. Weeks, Joshua Weinstock, Bruce Weir, Lu-Chen Weng, Jennifer Wessel, Cristen Willer, Kayleen Williams, L. Keoki Williams, Scott Williams, Carla Wilson, James Wilson, Lara Winterkorn, Quenna Wong, Baojun Wu, Joseph Wu, Huichun Xu, Lisa Yanek, Ivana Yang, Ketian Yu, Seyedeh Maryam Zekavat, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiaofeng Zhu, Elad Ziv, Michael Zody, and Sebastian Zoellner

Subjects
EWAS, DNA methylation, IgE, Asthma, RNA-Sequencing, Mendelian randomization, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Published
2023
Full Text
View/download PDF

6. P245: GUÍA application: Effectiveness in enhancing communication of genomic results in diverse, multilingual populations

Author

Priya Marathe, Sabrina Suckiel, Jacqueline Odgis, Katie Gallagher, Monisha Sebastin, Katherine Bonini, Kaitlyn Brown, Miranda Di Biase, Nicole Kelly, Michelle Ramos, Jessica Rodriguez, Laura Scarimbolo, Beverly Insel, Randi Zinberg, George Diaz, John Greally, Noura Abul-Husn, Laurie Bauman, Carol Horowitz, Bruce Gelb, Melissa Wasserstein, and Eimear Kenny

Subjects
Genetics, QH426-470, Medicine
Published
2023
Full Text
View/download PDF

7. P318: Impact of genetic counseling using GUÍA on diverse families’ understanding of genomic results: Finding from the NYCKidSeq randomized controlled trial

Author

Sabrina Suckiel, Nicole Kelly, Jacqueline Odgis, Katie Gallagher, Monisha Sebastin, Katherine Bonini, Priya Marathe, Kaitlyn Brown, Miranda Di Biase, Michelle Ramos, Jessica Rodriguez, Laura Scarimbolo, Beverly Insel, Randi Zinberg, George Diaz, John Greally, Noura Abul-Husn, Laurie Bauman, Carol Horowitz, Bruce Gelb, Melissa Wasserstein, and Eimear Kenny

Subjects
Genetics, QH426-470, Medicine
Published
2023
Full Text
View/download PDF

9. Mapping Semaphorins and Netrins in the Pathogenesis of Human Thoracic Aortic Aneurysms

Author

Dornazsadat Alebrahim, Mangala Nayak, Alison Ward, Patricia Ursomanno, Rebecca Shams, Annanina Corsica, Rayan Sleiman, Kissinger Hyppolite Fils, Michele Silvestro, Ludovic Boytard, Tarik Hadi, Bruce Gelb, and Bhama Ramkhelawon

Subjects
aneurysms, Semaphorins, netrins, extracellular matrix, vascular remodeling, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Thoracic aortic aneurysm (TAA) is a complex life-threatening disease characterized by extensive extracellular matrix (ECM) fragmentation and persistent inflammation, culminating in a weakened aorta. Although evidence suggests defective canonical signaling pathways in TAA, the full spectrum of mechanisms contributing to TAA is poorly understood, therefore limiting the scope of drug-based treatment. Here, we used a sensitive RNA sequencing approach to profile the transcriptomic atlas of human TAA. Pathway analysis revealed upregulation of key matrix-degrading enzymes and inflammation coincident with the axonal guidance pathway. We uncovered their novel association with TAA and focused on the expression of Semaphorins and Netrins. Comprehensive analysis of this pathway showed that several members were differentially expressed in TAA compared to controls. Immunohistochemistry revealed that Semaphorin4D and its receptor PlexinB1, similar to Netrin-1 proteins were highly expressed in damaged areas of TAA tissues but faintly detected in the vessel wall of non-diseased sections. It should be considered that the current study is limited by its sample size and the use of internal thoracic artery as control for TAA for the sequencing dataset. Our data determines important neuronal regulators of vascular inflammatory events and suggest Netrins and Semaphorins as potential key contributors of ECM degradation in TAA.

Published
2019
Full Text
View/download PDF

10. Quantification of Facial Allograft Edema During Acute Rejection

Author

Daniel Boczar, Hilliard Brydges, Ricardo Rodriguez Colon, Ogechukwu C. Onuh, Jorge Trilles, Bachar F. Chaya, Bruce Gelb, Daniel J. Ceradini, and Eduardo D. Rodriguez

Subjects
Adult, Graft Rejection, Male, Young Adult, Face, Photogrammetry, Edema, Humans, Surgery, Allografts, Software
Abstract

Acute rejection (AR) is a common complication in facial transplant (FT) patients associated with allograft edema and erythema. Our study aims to demonstrate the feasibility of using software-based 3-dimensional (3D) facial analysis to quantify edema as it resolves during/after AR treatment in an FT patient.Our patient is a 23-year-old man who underwent a face and bilateral hand allotransplant in August 2020. The Vectra H1 (Canfield, Fairfield, NJ) portable scanner was used to capture 3D facial images at 8 time points between postoperative day (POD) 392 and 539. The images were analyzed with the Vectra Software using a rejection-free image (POD 539) as a control.Edema increased in the periorbital, lower third, and submandibular regions before AR treatment (POD 392-415). At POD 448, total facial edema was reduced to near baseline values in response to plasmapheresis and thymoglobulin (+156.94 to +28.2 mL). The fastest and most notable response to treatment was seen in the periorbital region, while some edema remained in the submandibular (+19.79 mL) and right lower third (+8.65 mL) regions. On POD 465, after the initial improvement, the edema increased but was resolved with steroid use. Facial edema did not correlate with the histopathological evaluation in our patient.We demonstrated the feasibility of analyzing 3D facial images to quantify edema during/after AR treatment in an FT patient. Our analysis detected edema changes consistent with AR followed by an improvement after treatment. This technology shows promise for noninvasive monitoring of FT patients.

Published
2022

11. Structural variation across 138,134 samples in the TOPMed consortium

Author

Goo Jun, Adam English, Ginger Metcalf, Jianzhi Yang, Mark Chaisson, Nathan Pankratz, Vipin Menon, William Salerno, Olga Krasheninina, Albert Smith, John Lane, Thomas Blackwell, Hyun Min Kang, Sejal Salvi, Qingchang Meng, Hua Shen, Divya Pasham, Sravya Bhamidipati, Kavya Kottapalli, Donna Arnett, Allison Ashley-Koch, Paul Auer, KAthleen Beutel, Joshua Bis, John Blangero, Donald Bowden, Jennifer Brody, Brian Cade, Yii-Der Ida Chen, Michael Cho, Joanne Curran, Myriam Fornage, Barry Frredman, Tasha Fingerlin, Bruce Gelb, Lifang Hou, Yi-Jen Hung, John P Kane, Robert Kaplan, Wonji Kim, Ruth Loos, Gregory Marcus, Rasika Mathias, Stephen McGarvey, Courtney Montgomery, Take Naseri, Seyed Nouraie, Michael Preuss, Nicholette Palmer, Patricia Peyser, Laura Raffield, Aakrosh Ratan, Susan Redline, Muagututia Reupena, Jerome Rotter, Stephen Rich, Michiel Rienstra, Ingo Ruczinski, Vijay Sankaran, David Schwartz, Christine Seidman, Jonathan Seidman, Edwin Silverman, Jennifer Smith, Adrienne Stilp, Kent Taylor, Marilyn Telen, Scott Weiss, L. Keoki Williams, Baojun Wu, Lisa Yanek, Yingze Zhang, Jessica Lasky-Su, Marie-Claude Gingras, Susan Dutcher, Evan Eichler, Stacey Gabriel, Soren Germer, Ryan Kim, Karine Martinez, Deborah Nickerson, James Luo, Alexander Reiner, Richard Gibbs, Eric Boerwinkle, Goncaol Abecasis, and Fritz Sedlazeck

Subjects
Article
Abstract

Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a balance between comprehensiveness and precision. Here we present a catalog of 355,667 SVs (59.34% novel) across autosomes and the X chromosome (50bp+) from 138,134 individuals in the diverse TOPMed consortium. We describe our methodologies for SV inference resulting in high variant quality and >90% allele concordance compared to long-read de-novo assemblies of well-characterized control samples. We demonstrate utility through significant associations between SVs and important various cardio-metabolic and hematologic traits. We have identified 690 SV hotspots and deserts and those that potentially impact the regulation of medically relevant genes. This catalog characterizes SVs across multiple populations and will serve as a valuable tool to understand the impact of SV on disease development and progression.

Published
2023

12. Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease

Author

Daniel H. Katz, Usman A. Tahir, Alexander G. Bick, Akhil Pampana, Debby Ngo, Mark D. Benson, Zhi Yu, Jeremy M. Robbins, Zsu-Zsu Chen, Daniel E. Cruz, Shuliang Deng, Laurie Farrell, Sumita Sinha, Alec A. Schmaier, Dongxiao Shen, Yan Gao, Michael E. Hall, Adolfo Correa, Russell P. Tracy, Peter Durda, Kent D. Taylor, Yongmei Liu, W. Craig Johnson, Xiuqing Guo, Jie Yao, Yii-Der Ida Chen, Ani W. Manichaikul, Deepti Jain, Claude Bouchard, Mark A. Sarzynski, Stephen S. Rich, Jerome I. Rotter, Thomas J. Wang, James G. Wilson, Pradeep Natarajan, Robert E. Gerszten, Namiko Abe, Gonçalo Abecasis, Francois Aguet, Christine Albert, Laura Almasy, Alvaro Alonso, Seth Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum-Bowden, Kristin Ardlie, Dan Arking, Donna K. Arnett, Allison Ashley-Koch, Stella Aslibekyan, Tim Assimes, Paul Auer, Dimitrios Avramopoulos, Najib Ayas, Adithya Balasubramanian, John Barnard, Kathleen Barnes, R. Graham Barr, Emily Barron-Casella, Lucas Barwick, Terri Beaty, Gerald Beck, Diane Becker, Lewis Becker, Rebecca Beer, Amber Beitelshees, Emelia Benjamin, Takis Benos, Marcos Bezerra, Larry Bielak, Joshua Bis, Thomas Blackwell, John Blangero, Eric Boerwinkle, Donald W. Bowden, Russell Bowler, Jennifer Brody, Ulrich Broeckel, Jai Broome, Deborah Brown, Karen Bunting, Esteban Burchard, Carlos Bustamante, Erin Buth, Brian Cade, Jonathan Cardwell, Vincent Carey, Julie Carrier, April Carson, Cara Carty, Richard Casaburi, Juan P. Casas Romero, James Casella, Peter Castaldi, Mark Chaffin, Christy Chang, Yi-Cheng Chang, Daniel Chasman, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Michael Cho, Seung Hoan Choi, Lee-Ming Chuang, Mina Chung, Ren-Hua Chung, Clary Clish, Suzy Comhair, Matthew Conomos, Elaine Cornell, Carolyn Crandall, James Crapo, L. Adrienne Cupples, Joanne Curran, Jeffrey Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sean David, Colleen Davis, Michelle Daya, Mariza de Andrade, Lisa de las Fuentes, Paul de Vries, Michael DeBaun, Ranjan Deka, Dawn DeMeo, Scott Devine, Huyen Dinh, Harsha Doddapaneni, Qing Duan, Shannon Dugan-Perez, Ravi Duggirala, Jon Peter Durda, Susan K. Dutcher, Charles Eaton, Lynette Ekunwe, Adel El Boueiz, Patrick Ellinor, Leslie Emery, Serpil Erzurum, Charles Farber, Jesse Farek, Tasha Fingerlin, Matthew Flickinger, Myriam Fornage, Nora Franceschini, Chris Frazar, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Stacey Gabriel, Weiniu Gan, Shanshan Gao, Margery Gass, Heather Geiger, Bruce Gelb, Mark Geraci, Soren Germer, Robert Gerszten, Auyon Ghosh, Richard Gibbs, Chris Gignoux, Mark Gladwin, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, Sharon Graw, Kathryn J. Gray, Daniel Grine, Colin Gross, C. Charles Gu, Yue Guan, Namrata Gupta, David M. Haas, Jeff Haessler, Michael Hall, Yi Han, Patrick Hanly, Daniel Harris, Nicola L. Hawley, Jiang He, Ben Heavner, Susan Heckbert, Ryan Hernandez, David Herrington, Craig Hersh, Bertha Hidalgo, James Hixson, Brian Hobbs, John Hokanson, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Jianhong Hu, Yi-Jen Hung, Haley Huston, Chii Min Hwu, Marguerite Ryan Irvin, Rebecca Jackson, Cashell Jaquish, Jill Johnsen, Andrew Johnson, Craig Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert Kaplan, Sharon Kardia, Shannon Kelly, Eimear Kenny, Michael Kessler, Alyna Khan, Ziad Khan, Wonji Kim, John Kimoff, Greg Kinney, Barbara Konkle, Charles Kooperberg, Holly Kramer, Christoph Lange, Ethan Lange, Leslie Lange, Cathy Laurie, Cecelia Laurie, Meryl LeBoff, Jiwon Lee, Sandra Lee, Wen-Jane Lee, Jonathon LeFaive, David Levine, Dan Levy, Joshua Lewis, Xiaohui Li, Yun Li, Henry Lin, Honghuang Lin, Xihong Lin, Simin Liu, Yu Liu, Ruth J.F. Loos, Steven Lubitz, Kathryn Lunetta, James Luo, Ulysses Magalang, Michael Mahaney, Barry Make, Ani Manichaikul, Alisa Manning, JoAnn Manson, Lisa Martin, Melissa Marton, Susan Mathai, Rasika Mathias, Susanne May, Patrick McArdle, Merry-Lynn McDonald, Sean McFarland, Stephen McGarvey, Daniel McGoldrick, Caitlin McHugh, Becky McNeil, Hao Mei, James Meigs, Vipin Menon, Luisa Mestroni, Ginger Metcalf, Deborah A. Meyers, Emmanuel Mignot, Julie Mikulla, Nancy Min, Mollie Minear, Ryan L. Minster, Braxton D. Mitchell, Matt Moll, Zeineen Momin, May E. Montasser, Courtney Montgomery, Donna Muzny, Josyf C. Mychaleckyj, Girish Nadkarni, Rakhi Naik, Take Naseri, Sergei Nekhai, Sarah C. Nelson, Bonnie Neltner, Caitlin Nessner, Deborah Nickerson, Osuji Nkechinyere, Kari North, Jeff O’Connell, Tim O’Connor, Heather Ochs-Balcom, Geoffrey Okwuonu, Allan Pack, David T. Paik, Nicholette Palmer, James Pankow, George Papanicolaou, Cora Parker, Gina Peloso, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Patricia Peyser, Lawrence S. Phillips, Jacob Pleiness, Toni Pollin, Wendy Post, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuss, Bruce Psaty, Pankaj Qasba, Dandi Qiao, Zhaohui Qin, Nicholas Rafaels, Laura Raffield, Mahitha Rajendran, Vasan S. Ramachandran, D.C. Rao, Laura Rasmussen-Torvik, Aakrosh Ratan, Susan Redline, Robert Reed, Catherine Reeves, Elizabeth Regan, Alex Reiner, Muagututi’a Sefuiva Reupena, Ken Rice, Stephen Rich, Rebecca Robillard, Nicolas Robine, Dan Roden, Carolina Roselli, Jerome Rotter, Ingo Ruczinski, Alexi Runnels, Pamela Russell, Sarah Ruuska, Kathleen Ryan, Ester Cerdeira Sabino, Danish Saleheen, Shabnam Salimi, Sejal Salvi, Steven Salzberg, Kevin Sandow, Vijay G. Sankaran, Jireh Santibanez, Karen Schwander, David Schwartz, Frank Sciurba, Christine Seidman, Jonathan Seidman, Frédéric Sériès, Vivien Sheehan, Stephanie L. Sherman, Amol Shetty, Aniket Shetty, Wayne Hui-Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin Silverman, Robert Skomro, Albert Vernon Smith, Jennifer Smith, Josh Smith, Nicholas Smith, Tanja Smith, Sylvia Smoller, Beverly Snively, Michael Snyder, Tamar Sofer, Nona Sotoodehnia, Adrienne M. Stilp, Garrett Storm, Elizabeth Streeten, Jessica Lasky Su, Yun Ju Sung, Jody Sylvia, Adam Szpiro, Daniel Taliun, Hua Tang, Margaret Taub, Matthew Taylor, Simeon Taylor, Marilyn Telen, Timothy A. Thornton, Machiko Threlkeld, Lesley Tinker, David Tirschwell, Sarah Tishkoff, Hemant Tiwari, Catherine Tong, Russell Tracy, Michael Tsai, Dhananjay Vaidya, David Van Den Berg, Peter VandeHaar, Scott Vrieze, Tarik Walker, Robert Wallace, Avram Walts, Fei Fei Wang, Heming Wang, Jiongming Wang, Karol Watson, Jennifer Watt, Daniel E. Weeks, Joshua Weinstock, Bruce Weir, Scott T. Weiss, Lu-Chen Weng, Jennifer Wessel, Cristen Willer, Kayleen Williams, L. Keoki Williams, Carla Wilson, James Wilson, Lara Winterkorn, Quenna Wong, Joseph Wu, Huichun Xu, Lisa Yanek, Ivana Yang, Ketian Yu, Seyedeh Maryam Zekavat, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiaofeng Zhu, Michael Zody, and Sebastian Zoellner

Subjects
Adult, Male, Proteomics, Aging, Whole genome sequence analysis, Proteome, Clinical Sciences, Black People, Disease, Computational biology, race and ethnicity, Cardiorespiratory Medicine and Haematology, Cardiovascular, Article, proteomics, cardiovascular disease, Physiology (medical), Genetics, 2.1 Biological and endogenous factors, Humans, Medicine, Aetiology, Lung, Heart Disease - Coronary Heart Disease, and Blood Institute TOPMed (Trans-Omics for Precision Medicine) Consortium†, business.industry, Prevention, Human Genome, National Heart, Genomics, Blood proteins, Genetic architecture, Heart Disease, Good Health and Well Being, Cardiovascular System & Hematology, Cardiovascular Diseases, Public Health and Health Services, Female, Cardiology and Cardiovascular Medicine, business, Biotechnology, Genome-Wide Association Study
Abstract

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Published
2022

13. Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic Criteria for Vascular Changes

Author

Linda Cendales, Alton B Farris, Ivy A. Rosales, David Elder, Armando Gamboa-Dominguez, Bruce Gelb, Fadi Issa, Kadiyala Ravindra, Brian Nankivell, Simon Talbot, Xiaowei Xu, Dimitrios Moris, Cinthia Drachenberg, Jean Kanitakis, and Maria Angelica Selim

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2023

14. Report – Cost and Clinical Utility of WES and WGS in pediatric patients with suspected genetic disease

Author

Michael P. Douglas, Patricia A. Deverka, Bruce Gelb, Bart Ferket, Kristen Hassmiller Lich, Hadley Stevens Smith, Mary Norton, Jonathan Berg, Anne Slavotinek, Lucia Hindorff, and Kathryn Phillips

Abstract

Payer coverage for Exome Sequencing (ES) is becoming commonplace (albeit in some cases with prior authorization restrictions), coverage for Genome Sequencing (GS) is rare, with most payers considering it as investigational and not medically necessary. Previous studies had identified several concerns and challenges from the payer perspective.The objective of this study is to conduct a targeted literature review of the evidence describing the cost and clinical utility of GS and ES compared to standard of care (SoC) testing in children ≤18 years with suspected genetic disease.We conducted a systematic literature review to identify evidence for cost, diagnostic utility and clinical utility between SoC, ES, and GS in children (0-18 years) with suspected genetic diseases. We also identified list prices for individual tests from Concert Genetics. Descriptive analyses were conducted for cost and comparative effectiveness data.We identified five studies on costs of ES and GS, as well as data from concert genetics, and 62 studies of comparative effectiveness of GS or ES in pediatric patients There is limited evidence of GS over ES in the ability to effect change in management. Available evidence suggests that rapid over standard GS or ES is of greater benefit in the NICU/PICU setting vs. outpatient setting. Future clinical studies must include both diagnostic yield and clinical management outcomes in order to provide stakeholders with the necessary evidence to support decision-making on implementation and coverage.

Published
2022

15. Neither cardiac mitochondrial DNA variation nor copy number contribute to congenital heart disease risk

Author

Jon A.L. Willcox, Joshua T. Geiger, Sarah U. Morton, David McKean, Daniel Quiat, Joshua M. Gorham, Angela C. Tai, Steven DePalma, Daniel Bernstein, Martina Brueckner, Wendy K. Chung, Alessandro Giardini, Elizabeth Goldmuntz, Jonathan R. Kaltman, Richard Kim, Jane W. Newburger, Yufeng Shen, Deepak Srivastava, Martin Tristani-Firouzi, Bruce Gelb, George A. Porter, J.G. Seidman, and Christine E. Seidman

Subjects
Heart Defects, Congenital, DNA Copy Number Variations, Cardiovascular, DNA, Mitochondrial, Medical and Health Sciences, Congenital, Clinical Research, Report, Genetics, Humans, 2.1 Biological and endogenous factors, Aetiology, Genetics (clinical), Heart Defects, Pediatric, Genetics & Heredity, DNA, mitochondrial copy number, Biological Sciences, congenital heart disease, Mitochondria, Mitochondrial, genome sequencing, Heart Disease, mitochondrial genome, Mutation, Congenital Structural Anomalies
Abstract

The well-established manifestation of mitochondrial mutations in functional cardiac disease (e.g., mitochondrial cardiomyopathy) prompted the hypothesis that mitochondrial DNA (mtDNA) sequence and/or copy number (mtDNAcn) variation contribute to cardiac defects in congenital heart disease (CHD). MtDNAcns were calculated and rare, non-synonymous mtDNA mutations were identified in 1,837 CHD-affected proband-parent trios, 116 CHD-affected singletons, and 114 paired cardiovascular tissue/blood samples. The variant allele fraction (VAF) of heteroplasmic variants in mitochondrial RNA from 257 CHD cardiovascular tissue samples was also calculated. On average, mtDNA from blood had 0.14 rare variants and 52.9 mtDNA copies per nuclear genome per proband. No variation with parental age at proband birth or CHD-affected proband age was seen. mtDNAcns in valve/vessel tissue (320 ± 70) were lower than in atrial tissue (1,080 ± 320, p= 6.8E-21), which were lower than in ventricle tissue (1,340 ± 280, p= 1.4E-4). The frequency of rare variants in CHD-affected individual DNA was indistinguishable from the frequency in an unaffected cohort, and proband mtDNAcns did not vary from those of CHD cohort parents. In both the CHD and the comparison cohorts, mtDNAcns were significantly correlated between mother-child, father-child, and mother-father. mtDNAcns among people with European (mean= 52.0), African (53.0), and Asian haplogroups (53.5) were calculated and were significantly different for European and Asian haplogroups (p= 2.6E-3). Variant heteroplasmic fraction (HF) in blood correlated well with paired cardiovascular tissue HF (r= 0.975) and RNA VAF (r= 0.953), which suggests blood HF is a reasonable proxy for HF in heart tissue. We conclude that mtDNA mutations and mtDNAcns are unlikely to contribute significantly to CHD risk.

Published
2022

16. Cytomegalovirus-related Complications and Management in Facial Vascularized Composite Allotransplantation: An International Multicenter Retrospective Cohort Study

Author

Martin Kauke-Navarro, Adriana C. Panayi, Richard Formica, Francisco Marty, Neil Parikh, Sina Foroutanjazi, Ali-Farid Safi, Samir Mardini, Raymund R. Razonable, Emmanuel Morelon, Bruce Gelb, Eduardo Rodriguez, Patrik Lassus, and Bohdan Pomahac

Subjects
Vascularized Composite Allotransplantation, Transplantation, Cytomegalovirus Infections, Cytomegalovirus, Humans, Valganciclovir, Viremia, Antiviral Agents, Retrospective Studies
Abstract

There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation.This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed.We included 19 patients, 4 of whom received CMV high-risk transplants (D+/R-). CMV viremia was noted in 6 patients (all 4 D+/R- patients and 2 D-/R+), mostly within the first-year posttransplant, shortly after discontinuation of antiviral prophylaxis (median 2 mo). CMV disease occurred in 2 D+/R- patients. The high-risk group experienced relatively more rejection episodes per month follow-up. None of D+/R- patients suffered allograft loss due to rejection (longest follow-up: 121 mo).D+/R- patients were at increased risk of CMV-related complications. Although a higher number of rejections was noted in this group, none of the D+/R- patients lost their allograft or died because of CMV or rejection. Thus, CMV D+/R- face transplantation can likely be safely performed with prophylaxis, active surveillance, and prompt treatment.

Published
2022

17. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Priyadarshini Kachroo, Julian Hecker, Bo L. Chawes, Tarunveer S. Ahluwalia, Michael H. Cho, Dandi Qiao, Rachel S. Kelly, Su H. Chu, Yamini V. Virkud, Mengna Huang, Kathleen C. Barnes, Esteban G. Burchard, Celeste Eng, Donglei Hu, Juan C. Celedón, Michelle Daya, Albert M. Levin, Hongsheng Gui, L. Keoki Williams, Erick Forno, Angel C.Y. Mak, Lydiana Avila, Manuel E. Soto-Quiros, Michelle M. Cloutier, Edna Acosta-Pérez, Glorisa Canino, Klaus Bønnelykke, Hans Bisgaard, Benjamin A. Raby, Christoph Lange, Scott T. Weiss, Jessica A. Lasky-Su, Namiko Abe, Goncalo Abecasis, Christine Albert, Nicholette (Nichole) Palmer Allred, Laura Almasy, Alvaro Alonso, Seth Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum-Bowden, Dan Arking, Donna K. Arnett, Allison Ashley-Koch, Stella Aslibekyan, Tim Assimes, Paul Auer, Dimitrios Avramopoulos, John Barnard, Kathleen Barnes, R. Graham Barr, Emily Barron-Casella, Terri Beaty, Diane Becker, Lewis Becker, Rebecca Beer, Ferdouse Begum, Amber Beitelshees, Emelia Benjamin, Marcos Bezerra, Larry Bielak, Joshua Bis, Thomas Blackwell, John Blangero, Eric Boerwinkle, Ingrid Borecki, Russell Bowler, Jennifer Brody, Ulrich Broeckel, Jai Broome, Karen Bunting, Esteban Burchard, Jonathan Cardwell, Cara Carty, Richard Casaburi, James Casella, Mark Chaffin, Christy Chang, Daniel Chasman, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Yii-Der Ida Chen, Seung Hoan Choi, Lee-Ming Chuang, Mina Chung, Elaine Cornell, Adolfo Correa, Carolyn Crandall, James Crapo, L. Adrienne Cupples, Joanne Curran, Jeffrey Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sayantan Das, Sean David, Colleen Davis, Mariza de Andrade, Michael DeBaun, Ranjan Deka, Dawn DeMeo, Scott Devine, Ron Do, Qing Duan, Ravi Duggirala, Peter Durda, Susan Dutcher, Charles Eaton, Lynette Ekunwe, Patrick Ellinor, Leslie Emery, Charles Farber, Leanna Farnam, Tasha Fingerlin, Matthew Flickinger, Myriam Fornage, Nora Franceschini, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Stacey Gabriel, Weiniu Gan, Yan Gao, Margery Gass, Bruce Gelb, Xiaoqi (Priscilla) Geng, Soren Germer, Chris Gignoux, Mark Gladwin, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, C. Charles Gu, Yue Guan, Xiuqing Guo, Jeff Haessler, Michael Hall, Daniel Harris, Nicola Hawley, Jiang He, Ben Heavner, Susan Heckbert, Ryan Hernandez, David Herrington, Craig Hersh, Bertha Hidalgo, James Hixson, John Hokanson, Kramer Holly, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Haley Huston, Chii Min Hwu, Marguerite Ryan Irvin, Rebecca Jackson, Deepti Jain, Cashell Jaquish, Min A. Jhun, Jill Johnsen, Andrew Johnson, Craig Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert Kaplan, Sharon Kardia, Sekar Kathiresan, Laura Kaufman, Shannon Kelly, Eimear Kenny, Michael Kessler, Alyna Khan, Greg Kinney, Barbara Konkle, Charles Kooperberg, Stephanie Krauter, Ethan Lange, Leslie Lange, Cathy Laurie, Cecelia Laurie, Meryl LeBoff, Seunggeun Shawn Lee, Wen-Jane Lee, Jonathon LeFaive, David Levine, Dan Levy, Joshua Lewis, Yun Li, Honghuang Lin, Keng Han Lin, Simin Liu, Yongmei Liu, Ruth Loos, Steven Lubitz, Kathryn Lunetta, James Luo, Michael Mahaney, Barry Make, Ani Manichaikul, JoAnn Manson, Lauren Margolin, Lisa Martin, Susan Mathai, Rasika Mathias, Patrick McArdle, Merry-Lynn McDonald, Sean McFarland, Stephen McGarvey, Hao Mei, Deborah A. Meyers, Julie Mikulla, Nancy Min, Mollie Minear, Ryan L. Minster, Braxton Mitchell, May E. Montasser, Solomon Musani, Stanford Mwasongwe, Josyf C. Mychaleckyj, Girish Nadkarni, Rakhi Naik, Pradeep Natarajan, Sergei Nekhai, Deborah Nickerson, Kari North, Jeff O'Connell, Tim O'Connor, Heather Ochs-Balcom, James Pankow, George Papanicolaou, Margaret Parker, Afshin Parsa, Sara Penchev, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Patricia Peyser, Lawrence S. Phillips, Sam Phillips, Toni Pollin, Wendy Post, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuss, Dmitry Prokopenko, Bruce Psaty, Pankaj Qasba, Zhaohui Qin, Nicholas Rafaels, Laura Raffield, Vasan Ramachandran, D.C. Rao, Laura Rasmussen-Torvik, Aakrosh Ratan, Susan Redline, Robert Reed, Elizabeth Regan, Alex Reiner, Ken Rice, Stephen Rich, Dan Roden, Carolina Roselli, Jerome Rotter, Ingo Ruczinski, Pamela Russell, Sarah Ruuska, Kathleen Ryan, Phuwanat Sakornsakolpat, Shabnam Salimi, Steven Salzberg, Kevin Sandow, Vijay Sankaran, Christopher Scheller, Ellen Schmidt, Karen Schwander, David Schwartz, Frank Sciurba, Christine Seidman, Jonathan Seidman, Vivien Sheehan, Amol Shetty, Aniket Shetty, Wayne Hui-Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin Silverman, Jennifer Smith, Josh Smith, Nicholas Smith, Tanja Smith, Sylvia Smoller, Beverly Snively, Tamar Sofer, Nona Sotoodehnia, Adrienne Stilp, Elizabeth Streeten, Yun Ju Sung, Jessica Su-Lasky, Jody Sylvia, Adam Szpiro, Carole Sztalryd, Daniel Taliun, Hua Tang, Margaret Taub, Kent Taylor, Simeon Taylor, Marilyn Telen, Timothy A. Thornton, Lesley Tinker, David Tirschwell, Hemant Tiwari, Russell Tracy, Michael Tsai, Dhananjay Vaidya, Peter VandeHaar, Scott Vrieze, Tarik Walker, Robert Wallace, Avram Walts, Emily Wan, Fei Fei Wang, Karol Watson, Daniel E. Weeks, Bruce Weir, Scott Weiss, Lu-Chen Weng, Cristen Willer, Kayleen Williams, Carla Wilson, James Wilson, Quenna Wong, Huichun Xu, Lisa Yanek, Ivana Yang, Rongze Yang, Norann Zaghloul, Maryam Zekavat, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiuwen Zheng, Degui Zhi, Xiang Zhou, Michael Zody, and Sebastian Zoellner

Subjects
Adult, Costa Rica, Male, Pulmonary and Respiratory Medicine, Adolescent, Vital Capacity, Single-nucleotide polymorphism, Pedigree chart, Critical Care and Intensive Care Medicine, Young Adult, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Polymorphism (computer science), Forced Expiratory Volume, Humans, Medicine, SNP, 030212 general & internal medicine, Child, Asthma, Whole Genome Sequencing, business.industry, Middle Aged, respiratory system, medicine.disease, respiratory tract diseases, Minor allele frequency, 030228 respiratory system, Genetic epidemiology, Child, Preschool, Interferon Regulatory Factors, Immunology, Respiratory Physiological Phenomena, Female, Cardiology and Cardiovascular Medicine, business, Cell Adhesion Molecules
Abstract

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician’s diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10(−8) in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10(−6)). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

18. Abstract 11332: Integration of Protein Interactome Networks with Congenital Heart Disease Variants Reveals Candidate Disease Genes

Author

Barbara Gonzalez Teran, Maureen Pittman, Reuben Thomas, Franco Felix, Desmond Richmond-Buccola, Krishna Choudhary, Elisabetta Moroni, Colombo Giorgio, Arun Padmanabhan, Mauro Costa, Yu Huang, Michael Alexanian, Clara Lee, Bonie Cole, Kaitlen Samse-Knapp, Michael McGregor, Casey Gifford, Ruth Huttenhain, Bruce Gelb, Bruce Conklin, Brian L Black, Benoit Bruneau, Nevan Krogan, Katherine Pollard, and Deepak Srivastava

Subjects
Pediatric, Human Genome, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Cardiovascular, Stem Cell Research, Heart Disease, Good Health and Well Being, Cardiovascular System & Hematology, Physiology (medical), Genetics, Public Health and Health Services, Congenital Structural Anomalies, 2.1 Biological and endogenous factors, Stem Cell Research - Embryonic - Human, Aetiology, Cardiology and Cardiovascular Medicine, Biotechnology
Abstract

Congenital heart disease (CHD) is present in 1% of live births, yet despite large-scale genomic sequencing efforts, identification of causal mutations remains a challenge. We hypothesized that genetic determinants for CHDs may lie in the protein interactomes of GATA4 and TBX5, two transcription factors whose mutation cause CHDs. Defining the GATA4 or TBX5 interactomes in human cardiac progenitors via affinity purification-mass spectrometry and integrating the results with genetic data from the Pediatric Cardiac Genomic Consortium revealed an enrichment of de novo variants associated with CHD. A consolidative score that prioritized interactome members based on variant, gene, and proband features identified likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied and co-activated cardiac developmental genes, and the GLYR1 missense variant identified disrupted interaction with GATA4 and impaired transcriptional co-regulation in cardiomyocyte differentiation in vitro and cardiogenesis in vivo. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating the contribution of genetic variants in disease.

Published
2021

20. eP067: Diagnostic yield of genome sequencing versus targeted gene panel testing in diverse pediatric patients in the NYCKidSeq study

Author

Noura Abul-Husn, Nicole Kelly, Jessica Rodriguez, Avinash Abhyankar, Katherine Donohue, Kaitlyn Brown, Miranda DiBiase, Katie Gallagher, Saurav Guha, Nicolette Ioele, Priya Marathe, Jacqueline Odgis, Volkan Okur, Michelle Ramos, Atteeq Rehman, Monisha Sebastin, Amanda Thomas-Wilson, Randi Zinberg, George Diaz, Sabrina Suckiel, John Greally, Vaidehi Jobanputra, Carol Horowitz, Melissa Wasserstein, Eimear Kenny, and Bruce Gelb

Subjects
Genetics (clinical)
Published
2022

21. eP236: TeleKidSeq: Incorporating telehealth into clinical care of children from diverse backgrounds undergoing clinical genome sequencing

Author

Monisha Sebastin, Jacqueline Odgis, Sabrina Suckiel, Katherine Bonini, Miranda Di Biase, Kaitlyn Brown, Priya Marathe, Nicole Kelly, Michelle Ramos, Jessica Rodriguez, Karla Lopez Aguiniga, Jessenia Lopez, Estefany Maria, Michelle Rodriguez, Nicole Yelton, Charlotte Cunningham-Rundles, Katie Gallagher, Thomas McDonald, Patricia McGoldrick, Mimsie Robinson, Arye Rubinstein, Lisa Shulman, Steven Wolf, Elissa Yozawitz, Randi Zinberg, Noura Abul-Husn, Laurie Bauman, George Diaz, Bart Ferket, John Greally, Vaidehi Jobanputra, Bruce Gelb, Carol Horowitz, Eimear Kenny, and Melissa Wasserstein

Subjects
Genetics (clinical)
Published
2022

22. The ethics of testing and research of manufactured organs on brain-dead/recently deceased subjects

Author

Brendan, Parent, Bruce, Gelb, Stephen, Latham, Ariane, Lewis, Laura L, Kimberly, Arthur L, Caplan, and Stephen, Wall

Subjects
Brain dead, medicine.medical_specialty, Research ethics, Brain Death, Health (social science), Tissue and Organ Procurement, business.industry, Fair distribution, Health Policy, Brain, Economic shortage, Organ Transplantation, Tissue Donors, Medical services, 03 medical and health sciences, Issues, ethics and legal aspects, 0302 clinical medicine, Arts and Humanities (miscellaneous), Transplanted tissue, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, business, 030217 neurology & neurosurgery
Abstract

Over 115 000 people are waiting for life-saving organ transplants, of whom a small fraction will receive transplants and many others will die while waiting. Existing efforts to expand the number of available organs, including increasing the number of registered donors and procuring organs in uncontrolled environments, are crucial but unlikely to address the shortage in the near future and will not improve donor/recipient compatibility or organ quality. If successful, organ bioengineering can solve the shortage and improve functional outcomes. Studying manufactured organs in animal models has produced valuable data, but is not sufficient to understand viability in humans. Before risking manufactured organ experimentation in living humans, study of bioengineered organs in recently deceased humans would facilitate evaluation of the function of engineered tissues and the complex interactions between the host and the transplanted tissue. Although such studies do not pose risk to human subjects, they pose unique ethical challenges concerning the previous wishes of the deceased, rights of surviving family members, effective operation and fair distribution of medical services, and public transparency. This article investigates the ethical, legal and social considerations in performing engineered organ research on the recently deceased.

Published
2019

23. Health-Related Quality of Life in Children and Young Adults with Marfan Syndrome

Author

Jill C. Handisides, Danielle Hollenbeck-Pringle, Karen Uzark, Felicia L. Trachtenberg, Victoria L. Pemberton, Teresa W. Atz, Timothy J. Bradley, Elizabeth Cappella, Sylvia De Nobele, Georgeann Keh-Teng Groh, Michelle S. Hamstra, Rosalind Korsin, Jami C. Levine, Bergen Lindauer, Aimee Liou, Meghan K. Mac Neal, Larry W. Markham, Tonia Morrison, Kathleen A. Mussatto, Aaron K. Olson, Mary Ella M. Pierpont, Reed E. Pyeritz, Elizabeth A. Radojewski, Mary J. Roman, Mingfen Xu, Ronald V. Lacro, Gail Pearson, Mario Stylianou, Lynn Mahony, Lynn Sleeper, Sharon Tennstedt, Steven Colan, Gloria Klein, Lin Guey, Lisa Wruck, Thomas Travison, Shan Chen, Eric Gerstenberger, Tanya Olesker, David F. Teitel, Jane Newburger, Martha King, Carolyn Dunbar-Masterson, Andrea Posa, Quincy Nang, Cara Hass, Daphne Hsu, Wyman Lai, William Hellenbrand, Beth Printz, Richard Devereux, Greysi Sherwood, Victoria Vetter, Stephen Paridon, Marie Gleason, Nicole Mirarchi, Sandra DiLullo, Agbenu Ejembi, Ruth Morgan, D. Woodrow Benson, William Border, James Cnota, Haleh Heydarian, Jeanne James, Kathryn Hogan, Lois Bogenschutz, Mary Pat Benham, Teresa Barnard, Page A.W. Anderson, Jennifer S. Li, Stephanie Burns Wechsler, Amanda Cook, Charles Sang, Wesley Covitz, Lori Jo Sutton, Kari Crawford, Summer Roberts, Deborah Palmer, J. Philip Saul, Andrew Atz, Geoffrey Forbus, Patricia Infinger, Aparna Choudhury, LuAnn Minich, Richard Williams, Angela Yetman, Marian Shearrow, Michelle Robinson, June Porter, Brian McCrindle, Jennifer Russell, Jack Colman, Svetlana Khaikin, Nancy Slater, Harry C. Dietz, William J. Ravekes, Mary Rykiel, Elisabeth Sparks, Gretchen MacCarrick, Jennifer Leadroot, Charles Canter, Angela Sharkey, Alan Braverman, Cheryl Rainey, John L. Jefferies, Timothy Slesnick, Hugo Martinez, Andres Menesses, Tunu Tenende, David Liang, Elisabeth Merkel, Bart Loeys, Julie De Backer, Jan Maarten Cobben, Thierry Sluysmans, Anne De Paepe, Bruce Gelb, Shubhika Srivastava, Tejani Mendiz-Ramdeen, Constance Weismann, Emily Lawrence, Stephanie Chin, Helen Ko, Jen Le Yau, Steven Webber, Stacey Drant, Jane Luce, Kevin Stiegler, Cheryl Kinnard, Cheri Stewart, Sue Sommers, Carol Madison, Luciana Young, Megan Domenico, Kathryn Waitzman, Carla Lozano, Charles Baker, Erin Zielinski, Heidi Vander Velden, Alison Overman, Mark Lewin, Amy Payne, David Rimoin, Mitchel Pariani, Robert Siegel, Asim Rafique, Paul Grossfeld, Arlene Smith, Terri McLees-Palinkas, Steven D. Colan, Elif Seda Selamet Tierney, Shari Trevey, Marga Rivera, Michael Artman, Erle Austin, H. Scott Baldwin, Daniel Bernstein, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G. Paul Matherne, Kenneth G. Zahka, John Kugler, David J. Driscoll, Mark Galantowicz, Sally A. Hunsberger, Thomas J. Knight, Holly Taylor, Paediatric Genetics, and General Paediatrics

Subjects
Marfan syndrome, Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Severity of Illness Index, Losartan, Article, Marfan Syndrome, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neurodevelopmental disorder, Quality of life, 030225 pediatrics, Medicine, Health Status Indicators, Humans, 030212 general & internal medicine, Patient Reported Outcome Measures, Young adult, Child, Antihypertensive Agents, Health related quality of life, business.industry, Chronic pain, medicine.disease, humanities, Atenolol, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Quality of Life, Female, business, Psychosocial
Abstract

Objective: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. Study design: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. Results: Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤.003) and psychosocial (P

Published
2019

24. Cathepsin K Deficiency Ameliorates Systemic Lupus Erythematosus-like Manifestations in

Author

Yi, Zhou, Huimei, Chen, Li, Liu, Xueqing, Yu, Galina K, Sukhova, Min, Yang, Vasileios C, Kyttaris, Isaac E, Stillman, Bruce, Gelb, Peter, Libby, George C, Tsokos, and Guo-Ping, Shi

Subjects
Mice, Inbred MRL lpr, Membrane Glycoproteins, Cathepsin K, Autoimmunity, Complement C3, Kidney, Lupus Nephritis, T-Lymphocytes, Regulatory, Article, Mice, Inbred C57BL, Mice, Glomerulonephritis, Toll-Like Receptor 7, Immunoglobulin G, Animals, Lupus Erythematosus, Systemic, fas Receptor, Spleen
Abstract

Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but it is also inducible under inflammatory conditions. Faslpr mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus (SLE)-like manifestations. While normal mouse kidneys expressed negligible CatK, those from Faslpr mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Faslpr mice also showed elevated serum CatK levels. CatK deficiency in Faslpr mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies. CatK contributed to Faslpr mouse autoimmunity and pathology in part by its activity in Toll-like receptor-7 (TLR7) proteolytic processing and consequent regulatory T cell (Treg) biology. Elevated TLR7 expression and proteolytic processing in Faslpr mouse kidneys and Treg cells showed significantly reduced levels in CatK-deficient mice, leading to increased spleen and kidney Treg content. Purified CD4+CD25highFoxp3+ Treg cells from CatK-deficient mice doubled their immunosuppressive activity against T effector cells, compared to those from CatK-sufficient mice. In Faslpr mice, repopulation of purified Treg cells from CatK-sufficient mice reduced spleen sizes, autoantibody titers, and glomerulus C3 and IgG deposition, and increased splenic and kidney Treg cell contents. Treg cells from CatK-deficient mice had significantly more potency than CatK-sufficient Treg cells in reducing spleen sizes, serum autoantibody titers, and glomerulus C3 deposition, and in increasing splenic and kidney Treg cell content. This study established a possible role of CatK in TLR7 proteolytic activation, Treg immunosuppressive activity, and lupus autoimmunity and pathology.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results