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Research project

Does epigenetic methylation explain the gender-switch in adolescent asthma?

Project overview

This proposal focuses on studies of epigenetic mechanisms of asthma during the period of adolescent transition, which encompasses hormonal and body mass index changes, growth effects, and the possible use of contraceptives, acetaminophen for relief of menstrual symptoms, and nicotine. Many studies have indicated a gender reversal of asthma prevalence during this transition due to a higher incidence and lower remission in girls. This provides a great opportunity to investigate the epigenetic mechanisms of asthma and associated risk factors during adolescence. Specifically, we will 1) assess genome-wide DNA methylation (DNA-M) at CpG sites using blood DNA samples taken before and after adolescent transition; identify CpGs associated with asthma transition and CpGs showing gender specificity in these associations; 2) test the association of asthma risk factors with DNA-M or its changes on these selected sites; 3) evaluate the agreement of methylation in peripheral blood leukocytes (PBL) and bronchial epithelial cells (BEC), and in PBL and in BEC, functionally assess the identified epigenetic marks in cis and trans via gene expressions and risk factors. Our overall hypothesis is: the reversal of asthma prevalence in adolescence can be explained by novel methylation difference between genders during the pre- to post-adolescent transition. We will test: (H1) DNA-M or its change across adolescence is associated with the change in asthma risk (TEMs), and the association is gender-specific (TGEMs). (H2) Adolescence-related, environmental, and socio-economic status (SES) risk factors are associated with DNA-M or its changes. (H3) DNA-M in PBL and BEC are correlated for CpG sites associated with asthma status. (H4) DNA-M of TEMs and TGEMs correlates with gene expression in PBL and in BEC and such correlation is gender specific, and (H5) gene expression is associated with TEMs and TGEMs- related risk factors. Expected findings will significant improve our understanding of gender-reversal of asthma prevalence in adolescence, thus provide a strong foundation for promoting asthma remission and predicting and preventing persistent and new onset asthma in adolescence. The results will help pediatricians and public health units to identify children at high risk of asthma in adolescence. Two comparable longitudinal birth cohorts will be investigated in this study. The Isle of Wight (IOW) birth cohort, established in 1989, is comprised of 1,456 children characterized for asthma and allergy at birth, 1, 2, 4, 10, and 18 years of age. The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in Bristol, established in 1991, includes 4,213 children characterized for asthma and allergy at ages 7-8 and 15-17 years. Both cohorts have extensive phenotype data, environmental exposure data, and DNA samples from pre- and post-adolescence. More importantly, PBL DNA-M have been measured for a large portion of subjects in each cohort.


Lead researcher

Professor John Holloway PhD, FHEA

Associate V-P Interdisciplinary Research

Research interests

  • Human genetics
  • Epigenetics
  • Respiratory Disease
Other researchers

Professor Hasan Arshad

Prof in Allergy & Clinical Immunology

Research outputs

Latha Kadalayil,
Md. Zahangir Alam,
Cory Haley White,
Akram Ghantous,
Esther Walton,
Olena Gruzieva,
Simon Kebede Merid,
Ashish Kumar,
Ritu P. Roy,
Olivia Solomon,
Karen Huen,
Brenda Eskenazi,
Peter Rzehak,
Veit Grote,
Jean-paul Langhendries,
Elvira Verduci,
Natalia Ferre,
Darek Gruszfeld,
Lu Gao,
Weihua Guan,
Xuehuo Zeng,
Enrique F. Schisterman,
John F. Dou,
Kelly M. Bakulski,
Jason I. Feinberg,
Munawar Hussain Soomro,
Giancarlo Pesce,
Nour Baiz,
Elena Isaevska,
Michelle Plusquin,
Marina Vafeiadi,
Theano Roumeliotaki,
Sabine A.S. Langie,
Arnout Standaert,
Catherine Allard,
Patrice Perron,
Luigi Bouchard,
Evelien R. Van Meel,
Janine F. Felix,
Vincent W.V. Jaddoe,
Paul D. Yousefi,
Cecilia H. Ramlau-hansen,
Caroline L. Relton,
Elmar W. Tobi,
Anne P. Starling,
Ivana V. Yang,
Maria Llambrich,
Gillian Santorelli,
Johanna Lepeule,
Lucas A. Salas,
Mariona Bustamante,
Susan L. Ewart,
Hongmei Zhang,
Wilfried Karmaus,
Stefan Röder,
Ana Claudia Zenclussen,
Jianping Jin,
Wenche Nystad,
Christian M. Page,
Maria Magnus,
Dereje D. Jima,
Cathrine Hoyo,
Rachel L. Maguire,
Tuomas Kvist,
Darina Czamara,
Katri Räikkönen,
Tong Gong,
Vilhelmina Ullemar,
Sheryl L. Rifas-shiman,
Emily Oken,
Catarina Almqvist,
Robert Karlsson,
Jari Lahti,
Susan K. Murphy,
Siri E. Håberg,
Stephanie London,
Gunda Herberth,
Jordi Sunyer,
Regina Grazuleviciene,
Dana Dabelea,
Régine P.M. Steegers-Theunissen,
Ellen A. Nohr,
Thorkild I.A. Sørensen,
Liesbeth Duijts,
Marie-france Hivert,
Vera Nelen,
Maja Popovic,
Manolis Kogevinas,
Tim S. Nawrot,
Zdenko Herceg,
Isabella Annesi-maesano,
M. Daniele Fallin,
Edwina Yeung,
Carrie V. Breton,
Berthold Koletzko,
Nina Holland,
Joseph L. Wiemels,
Erik Melén,
Gemma C. Sharp,
Matt J. Silver,
Faisal I. Rezwan,
& John W. Holloway
, 2023 , Clinical Epigenetics , 15 (1)
Type: article
Shakiba Eslamimehr,
A Daniel Jones,
Thilani M Anthony,
Susan Ewart,
Rui Luo,
Nandini Mukherjee,
Parnian Kheirkhah Rahimabad,
Su Chen,
& Wilfried Karmaus
, 2022 , Environmental Epigenetics , 8 (1) , dvac002
Type: article
Lisa M. Wheatley,
Cecilie Svanes,
Malcolm R. Sears,
Carrie Breton,
Alexey V. Fedulov,
Eric Nilsson,
Donata Vercelli,
Hongmei Zhang,
Alkis Togias,
, 2022 , Clinical & Experimental Allergy , 52 (11) , 1264--1275
Type: review
Dilini M. Kothalawala,
Veronique B. N. Weiss,
Latha Kadalayil,
Raquel Granell,
John A. Curtin,
Clare S. Murray,
Angela Simpson,
Adnan Custovic,
Faisal I. Rezwan,
, 2022 , Pediatric Allergy and Immunology , 33 (4) , e13777
Type: article
Liang Li,
Hongmei Zhang,
Susan Ewart,
Caroline L. Relton,
& Wilfried Karmaus
, 2022 , ERJ Open Research , 8 (1)
Type: article