학술논문
Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthmaResearch in context
Document Type
article
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; Sebastian Zoellner
Source
EBioMedicine, Vol 95, Iss , Pp 104758- (2023)
Subject
Language
English
ISSN
2352-3964
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