Accès ouvert déclaré
2023
article
Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma
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, Namiko Abe, Gonçalo R. Abecasis, François Aguet, Christine M. Albert, Laura Almasy, Álvaro Alonso, Seth A. Ament, Peter H. Anderson, Pramod Anugu, Deborah Applebaum‐Bowden, Kristin Ardlie, Dan E. Arking, Donna K. Arnett, Allison E. Ashley‐Koch, Stella Aslibekyan, Tim Assimes, Paul L. Auer, Dimitrios Avramopoulos, Najib Ayas, Adithya Balasubramanian, John Barnard, Kathleen C. Barnes, R. Graham Barr, Emily Barron‐Casella, Lucas Barwick, Terri H. Beaty, Gerald J. Beck, Diane M. Becker, Lewis C. Becker, Rebecca Beer, Amber L. Beitelshees, Emelia J. Benjamin, Takis Benos, Marcos Bezerra, Larry Bielak, Joshua C. Bis, Thomas W. Blackwell, John Blangero, Nathan R. Blue, Eric Boerwinkle, Donald W. Bowden, Russell P. Bowler, Jennifer A. Brody, Ulrich Broeckel, Jai Broome, Deborah Brown, Karen Bunting, Esteban G. Burchard, Carlos D. Bustamante, Erin Buth, Brian E. Cade, Jonathan Cardwell, Vincent J. Carey, Julie Carrier, April P. Carson, Cara L. Carty, Richard Casaburi, Juan P. Romero, James F. Casella, Peter J. Castaldi, Mark Chaffin, Christy Chang, Yi‐Cheng Chang, Daniel I. Chasman, Sameer Chavan, Bo-Juen Chen, Wei‐Min Chen, Yii‐Der Ida Chen, Michael Cho, Seung Hoan Choi, Lee‐Ming Chuang, Mina K. Chung, Ren‐Hua Chung, Clary B. Clish, Suzy Comhair, Matthew P. Conomos, Elaine Cornell, Adolfo Correa, Carolyn Crandall, James D. Crapo, L. Adrienne Cupples, Joanne E. Curran, Jeffrey L. Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sean P. David, Colleen Davis, Michelle Daya, Mariza de Andrade, Lisa de las Fuentes, Paul S. de Vries, Michael R. DeBaun, Ranjan Deka, Dawn L. DeMeo, Scott E. Devine, Huyen Dinh, HarshaVardhan Doddapaneni, Qing Duan, Shannon Dugan‐Perez, Ravi Duggirala, Jon Peter Durda, Susan K. Dutcher, Charles B. Eaton, Lynette Ekunwe, Adel Boueiz, Patrick T. Ellinor, Leslie S. Emery, Serpil C. Erzurum, Charles R. Farber, Jesse Farek, Tasha E. 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 D. Gelb, Mark W. Geraci, Søren Germer, Robert E. Gerszten, Auyon Ghosh, Richard A. Gibbs, Chris Gignoux, Mark T. Gladwin, David C. Glahn, Stephanie M. Gogarten, Da‐Wei Gong, Harald H.H. Göring, Sharon Graw, Kathryn J. Gray, Daniel Grine, Colin Gross, C. Charles Gu, Yue Guan, Xiuqing Guo, Namrata Gupta, Jeff Haessler, Michael E. Hall, Yi Han, Patrick J. Hanly, Daniel Harris, Nicola L. Hawley, Jiang He, Ben Heavner, Susan R. Heckbert, Ryan D. Hernandez, David M. Herrington, Craig P. Hersh, Bertha Hidalgo, James E. Hixson, Brian D. Hobbs, John E. Hokanson, Elliott Hong, Karin F. Hoth, Chao A. Hsiung, Taobo Hu, Yi‐Jen Hung, Haley Huston, Chii Min Hwu, Marguerite R. Irvin, Rebecca D. Jackson, Deepti Jain, Cashell E. Jaquish, Jill M. Johnsen, Andrew D. Johnson, Craig Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert C. Kaplan, Sharon L. R. Kardia, Shannon Kelly, Eimear E. Kenny, Michael Kessler, Alyna Khan, Ziad Khan, Wonji Kim, John Kimoff, Gregory L. Kinney, Barbara A. Konkle, Charles Kooperberg, Holly Kramer, Christoph Lange, Ethan M. Lange, Leslie A. Lange, Cathy C. Laurie, Cecelia Laurie, Meryl S. LeBoff, Jiwon Lee, Wen‐Jane Lee, Jonathon LeFaive, David Levine, Daniel Levy, Joshua P. Lewis, Xiaohui Li, Yun Li, Henry J. Lin, Honghuang Lin, Xihong Lin, Simin Liu, Ching‐Ti Liu, Yu Liu, Ruth J. F. Loos, Steven A. Lubitz, Kathryn L. Lunetta, James Luo, Ulysses J. Magalang, Michael C. Mahaney, Barry J. Make, Ani Manichaikul, Alisa K. Manning, JoAnn E. Manson, Lisa W. Martin, Melissa Marton, Susan Mathai, Rasika A. Mathias, Susanne May, Patrick F. McArdle, Merry‐Lynn McDonald, Sean McFarland, Stephen T. McGarvey, Daniel McGoldrick, Caitlin McHugh, Becky McNeil, Hao Mei, James B. Meigs, Vipin K. Menon, Luisa Mestroni, Ginger Metcalf, Deborah A. Meyers, Emmanuel Mignot, Julie Mikulla, Yuan‐I Min, Mollie Minear, Ryan L. Minster, Braxton D. Mitchell, Matt Moll, Zeineen Momin, May E. Montasser, Courtney G. Montgomery, Donna M. Muzny, Josyf C. Mychaleckyj, Girish N. Nadkarni, Rakhi P. Naik, Take Naseri, Pradeep Natarajan, Sergeï Nekhai, Sarah C. Nelson, Bonnie Neltner, Caitlin Nessner, Deborah A. Nickerson, Osuji Nkechinyere, Kari E. North, Jeff O’Connell, Tim O’Connor, Heather M. Ochs‐Balcom, Geoffrey Okwuonu, Allan I Pack, David T. Paik, James S. Pankow, George Papanicolaou, Gina M. Peloso, Juan M. Peralta, Marco Perez, James A. Perry, Patricia A. Peyser, Lawrence S. Phillips, Jacob Pleiness, Toni I. Pollin, Wendy S. Post, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuß, Bruce M. Psaty, Pankaj Qasba, Dandi Qiao, Zhaohui Qin, Nicholas Rafaels, Laura M. Raffield, Mahitha Rajendran, Ramachandran S. Vasan, D. C. Rao, Laura J. Rasmussen‐Torvik, Aakrosh Ratan, Susan Redline, Robert M. Reed, Catherine Reeves, Elizabeth A. Regan, Alex P. Reiner, Muagututi‘a Sefuiva Reupena, Kenneth Rice, Stephen S. Rich, Rébecca Robillard, Nicolas Robine, Dan M. Roden, Carolina Roselli, Jerome I. Rotter, Ingo Ruczinski, Alexi Runnels, Pamela Russell, Sarah Ruuska, Kathleen A. Ryan, Éster Cerdeira Sabino, Danish Saleheen, Shabnam Salimi, Sejal Salvi, Steven L. Salzberg, Kevin Sandow, Vijay G. Sankaran, Jireh Santibanez, Karen Schwander, David A. Schwartz, Frank C. Sciurba, Christine Seidman, Jonathan G. Seidman, Frédéric Sériès, Vivien Sheehan, Stephanie L. Sherman, Amol C. Shetty, Aniket Shetty, Wayne Hui-Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin K. Silverman, Robert Skomro, Albert V. Smith, Jennifer A. Smith, J. G. Smith, Nicholas L. Smith, Tanja Smith, Sylvia Smoller, Beverly M. Snively, M Snyder, Tamar Sofer, Nona Sotoodehnia, Adrienne M. Stilp, Garrett Storm, Elizabeth A. Streeten, Jessica Lasky‐Su, Jody Sylvia, Adam A. Szpiro, Daniel Taliun, Hua Tang, Margaret A. Taub, Kent D. Taylor, Matthew R.G. Taylor, Simeon I. Taylor, Marilyn J. Telen, Timothy A. Thornton, Machiko Threlkeld, Lesley Tinker, David Tirschwell, Sarah A. Tishkoff, Hemant K. Tiwari, Catherine Tong, Russell P. Tracy, Michael Y. Tsai, Dhananjay Vaidya, Peter VandeHaar, Scott Vrieze, Tarik Walker, Robert B. Wallace, Avram Walts, Fei Fei Wang, Heming Wang, Jiongming Wang, Karol E. Watson, Jennifer Watt, Daniel E. Weeks, Joshua Weinstock, Bruce S. Weir, Lu‐Chen Weng, Jennifer Wessel, Cristen J. Willer, Kayleen Williams, L. Keoki Williams, Scott M. Williams, Carla Wilson, James G. Wilson, Lara Winterkorn, Quenna Wong, Baojun Wu, Joseph Wu, Huichun Xu, Lisa R. Yanek, Ivana V. Yang, Ketian Yu, Seyedeh M. Zekavat, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiaofeng Zhu, Elad Ziv, Michael C. Zody, Sebastian Zoellner, George O'connor
20Citations signalées — pas une note de qualité
6Institutions déclarées
1Pays d’affiliation déclarés
Résumé fourni par la source
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 < 7.94E-04) that can be explored as potential therapeutic targets. INTERPRETATION: By integrating eQTM and MR analyses in general and clinical asthma populations, our findings provide a deeper understanding of the multidimensional inter-relations of DNA methylation, gene expression, and IgE levels. FUNDING: US NIH/NHLBI grants: P01HL132825, K99HL159234. N01-HC-25195 and HHSN268201500001I.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma
- Date Crossref
- 01/09/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.
Institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Sujets associés
Asthma and respiratory diseasesEpigenetics and DNA MethylationGenetic Associations and Epidemiology