Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthmaResearch in context
In: EBioMedicine, Jg. 95 (2023-09-01), Heft 104758-
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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
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Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthmaResearch in context
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| Autor/in / Beteiligte Person: | Recto, Kathryn ; Kachroo, Priyadarshini ; Huan, Tianxiao ; David Van Den Berg ; Gha Young Lee ; Bui, Helena ; Dong Heon Lee ; Gereige, Jessica ; Yao, Chen ; Hwang, Shih-Jen ; Joehanes, Roby ; Weiss, Scott T. ; O’Connor, George T. ; Levy, Daniel ; DeMeo, Dawn L. ; Abe, Namiko ; Abecasis, Gonçalo ; Aguet, Francois ; Albert, Christine ; Almasy, Laura ; Alonso, Alvaro ; Ament, Seth ; Anderson, Peter ; Anugu, Pramod ; Applebaum-Bowden, Deborah ; Ardlie, Kristin ; Arking, Dan ; Arnett, Donna K. ; Ashley-Koch, Allison ; Aslibekyan, Stella ; Assimes, Tim ; Auer, Paul ; Avramopoulos, Dimitrios ; Ayas, Najib ; Balasubramanian, Adithya ; Barnard, John ; Barnes, Kathleen ; R. Graham Barr ; Barron-Casella, Emily ; Barwick, Lucas ; Beaty, Terri ; Beck, Gerald ; Becker, Diane ; Becker, Lewis ; Beer, Rebecca ; Beitelshees, Amber ; Benjamin, Emelia ; Benos, Takis ; Bezerra, Marcos ; Bielak, Larry ; Bis, Joshua ; Blackwell, Thomas ; Blangero, John ; Blue, Nathan ; Boerwinkle, Eric ; Bowden, Donald W. ; Bowler, Russell ; Brody, Jennifer ; Broeckel, Ulrich ; Broome, Jai ; Brown, Deborah ; Bunting, Karen ; Burchard, Esteban ; Bustamante, Carlos ; Buth, Erin ; Cade, Brian ; Cardwell, Jonathan ; Carey, Vincent ; Carrier, Julie ; Carson, April P. ; Carty, Cara ; Casaburi, Richard ; Juan P. Casas Romero ; Casella, James ; Castaldi, Peter ; Chaffin, Mark ; Chang, Christy ; Chang, Yi-Cheng ; Chasman, Daniel ; Chavan, Sameer ; Chen, Bo-Juen ; Chen, Wei-Min ; Yii-Der Ida Chen ; Cho, Michael ; Seung Hoan Choi ; Chuang, Lee-Ming ; Chung, Mina ; Chung, Ren-Hua ; Clish, Clary ; Comhair, Suzy ; Conomos, Matthew ; Cornell, Elaine ; Correa, Adolfo ; Crandall, Carolyn ; Crapo, James ; L. Adrienne Cupples ; Curran, Joanne ; Curtis, Jeffrey ; Custer, Brian ; Damcott, Coleen ; Darbar, Dawood ; David, Sean ; Davis, Colleen ; Daya, Michelle ; Mariza de Andrade ; Lisa de las Fuentes ; Paul de Vries ; DeBaun, Michael ; Deka, Ranjan ; DeMeo, Dawn ; Devine, Scott ; Dinh, Huyen ; Doddapaneni, Harsha ; Duan, Qing ; Dugan-Perez, Shannon ; Duggirala, Ravi ; Jon Peter Durda ; Dutcher, Susan K. ; Eaton, Charles ; Ekunwe, Lynette ; Adel El Boueiz ; Ellinor, Patrick ; Emery, Leslie ; Erzurum, Serpil ; Farber, Charles ; Farek, Jesse ; Fingerlin, Tasha ; Flickinger, Matthew ; Fornage, Myriam ; Franceschini, Nora ; Frazar, Chris ; Fu, Mao ; Fullerton, Stephanie M. ; Fulton, Lucinda ; Gabriel, Stacey ; Gan, Weiniu ; Gao, Shanshan ; Gao, Yan ; Gass, Margery ; Geiger, Heather ; Gelb, Bruce ; Geraci, Mark ; Germer, Soren ; Gerszten, Robert ; Ghosh, Auyon ; Gibbs, Richard ; Gignoux, Chris ; Gladwin, Mark ; Glahn, David ; Gogarten, Stephanie ; Gong, Da-Wei ; Goring, Harald ; Graw, Sharon ; Gray, Kathryn J. ; Grine, Daniel ; Gross, Colin ; C. Charles Gu ; Guan, Yue ; Guo, Xiuqing ; Gupta, Namrata ; Haessler, Jeff ; Hall, Michael ; Han, Yi ; Hanly, Patrick ; Harris, Daniel ; Hawley, Nicola L. ; He, Jiang ; Heavner, Ben ; Heckbert, Susan ; Hernandez, Ryan ; Herrington, David ; Hersh, Craig ; Hidalgo, Bertha ; Hixson, James ; Hobbs, Brian ; Hokanson, John ; Hong, Elliott ; Hoth, Karin ; Chao (Agnes) Hsiung ; Hu, Jianhong ; Hung, Yi-Jen ; Huston, Haley ; Chii Min Hwu ; Marguerite Ryan Irvin ; Jackson, Rebecca ; Jain, Deepti ; Jaquish, Cashell ; Johnsen, Jill ; Johnson, Andrew ; Johnson, Craig ; Johnston, Rich ; Jones, Kimberly ; Hyun Min Kang ; Kaplan, Robert ; Kardia, Sharon ; Kelly, Shannon ; Kenny, Eimear ; Kessler, Michael ; Khan, Alyna ; Khan, Ziad ; Kim, Wonji ; Kimoff, John ; Kinney, Greg ; Konkle, Barbara ; Kooperberg, Charles ; Kramer, Holly ; Lange, Christoph ; Lange, Ethan ; Lange, Leslie ; Laurie, Cathy ; Laurie, Cecelia ; LeBoff, Meryl ; Lee, Jiwon ; Lee, Sandra ; Lee, Wen-Jane ; LeFaive, Jonathon ; Levine, David ; Lewis, Joshua ; Li, Xiaohui ; Li, Yun ; Lin, Henry ; Lin, Honghuang ; Lin, Xihong ; Liu, Simin ; Liu, Yongmei ; Liu, Yu ; Ruth J.F. Loos ; Lubitz, Steven ; Lunetta, Kathryn ; Luo, James ; Magalang, Ulysses ; Mahaney, Michael ; Make, Barry ; Manichaikul, Ani ; Manning, Alisa ; Manson, JoAnn ; Martin, Lisa ; Marton, Melissa ; Mathai, Susan ; Mathias, Rasika ; May, Susanne ; McArdle, Patrick ; McDonald, Merry-Lynn ; McFarland, Sean ; McGarvey, Stephen ; McGoldrick, Daniel ; McHugh, Caitlin ; McNeil, Becky ; Mei, Hao ; Meigs, James ; Menon, Vipin ; Mestroni, Luisa ; Metcalf, Ginger ; Meyers, Deborah A. ; Mignot, Emmanuel ; Mikulla, Julie ; Min, Nancy ; Minear, Mollie ; Minster, Ryan L. ; Mitchell, Braxton D. ; Moll, Matt ; Momin, Zeineen ; Montasser, May E. ; Montgomery, Courtney ; Muzny, Donna ; Mychaleckyj, Josyf C. ; Nadkarni, Girish ; Naik, Rakhi ; Naseri, Take ; Natarajan, Pradeep ; Nekhai, Sergei ; Nelson, Sarah C. ; Neltner, Bonnie ; Nessner, Caitlin ; Nickerson, Deborah ; Nkechinyere, Osuji ; North, Kari ; O'Connell, Jeff ; O'Connor, Tim ; Ochs-Balcom, Heather ; Okwuonu, Geoffrey ; Pack, Allan ; Paik, David T. ; Palmer, Nicholette ; Pankow, James ; Papanicolaou, George ; Parker, Cora ; Peloso, Gina ; Juan Manuel Peralta ; Perez, Marco ; Perry, James ; Peters, Ulrike ; Peyser, Patricia ; Phillips, Lawrence S. ; Pleiness, Jacob ; Pollin, Toni ; Post, Wendy ; Julia Powers Becker ; Meher Preethi Boorgula ; Preuss, Michael ; Psaty, Bruce ; Qasba, Pankaj ; Qiao, Dandi ; Qin, Zhaohui ; Rafaels, Nicholas ; Raffield, Laura ; Rajendran, Mahitha ; Ramachandran, Vasan S. ; Rao, D.C. ; Rasmussen-Torvik, Laura ; Ratan, Aakrosh ; Redline, Susan ; Reed, Robert ; Reeves, Catherine ; Regan, Elizabeth ; Reiner, Alex ; Muagututi‘a Sefuiva Reupena ; Rice, Ken ; Rich, Stephen ; Robillard, Rebecca ; Robine, Nicolas ; Roden, Dan ; Roselli, Carolina ; Rotter, Jerome ; Ruczinski, Ingo ; Runnels, Alexi ; Russell, Pamela ; Ruuska, Sarah ; Ryan, Kathleen ; Ester Cerdeira Sabino ; Saleheen, Danish ; Salimi, Shabnam ; Salvi, Sejal ; Salzberg, Steven ; Sandow, Kevin ; Sankaran, Vijay G. ; Santibanez, Jireh ; Schwander, Karen ; Schwartz, David ; Sciurba, Frank ; Seidman, Christine ; Seidman, Jonathan ; Sériès, Frédéric ; Sheehan, Vivien ; Sherman, Stephanie L. ; Shetty, Amol ; Shetty, Aniket ; Wayne Hui-Heng Sheu ; M. Benjamin Shoemaker ; Silver, Brian ; Silverman, Edwin ; Skomro, Robert ; Albert Vernon Smith ; Smith, Jennifer ; Smith, Josh ; Smith, Nicholas ; Smith, Tanja ; Smoller, Sylvia ; Snively, Beverly ; Snyder, Michael ; Sofer, Tamar ; Sotoodehnia, Nona ; Stilp, Adrienne M. ; Storm, Garrett ; Streeten, Elizabeth ; Jessica Lasky Su ; Yun Ju Sung ; Sylvia, Jody ; Szpiro, Adam ; Taliun, Daniel ; Tang, Hua ; Taub, Margaret ; Taylor, Kent ; Taylor, Matthew ; Taylor, Simeon ; Telen, Marilyn ; Thornton, Timothy A. ; Threlkeld, Machiko ; Tinker, Lesley ; Tirschwell, David ; Tishkoff, Sarah ; Tiwari, Hemant ; Tong, Catherine ; Tracy, Russell ; Tsai, Michael ; Vaidya, Dhananjay ; VandeHaar, Peter ; Vrieze, Scott ; Walker, Tarik ; Wallace, Robert ; Walts, Avram ; Fei Fei Wang ; Wang, Heming ; Wang, Jiongming ; Watson, Karol ; Watt, Jennifer ; Weeks, Daniel E. ; Weinstock, Joshua ; Weir, Bruce ; Weng, Lu-Chen ; Wessel, Jennifer ; Willer, Cristen ; Williams, Kayleen ; L. Keoki Williams ; Williams, Scott ; Wilson, Carla ; Wilson, James ; Winterkorn, Lara ; Wong, Quenna ; Wu, Baojun ; Wu, Joseph ; Xu, Huichun ; Yanek, Lisa ; Yang, Ivana ; Yu, Ketian ; Seyedeh Maryam Zekavat ; Zhang, Yingze ; Snow Xueyan Zhao ; Zhao, Wei ; Zhu, Xiaofeng ; Ziv, Elad ; Zody, Michael ; Zoellner, Sebastian |
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| Zeitschrift: | EBioMedicine, Jg. 95 (2023-09-01), Heft 104758- |
| Veröffentlichung: | Elsevier, 2023 |
| Medientyp: | academicJournal |
| ISSN: | 2352-3964 (print) |
| DOI: | 10.1016/j.ebiom.2023.104758 |
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