Newborn DNA methylation and asthma acquisition across adolescence and early adulthood

被引:6
作者
Li, Liang [1 ]
Holloway, John W. [2 ]
Ewart, Susan [3 ]
Arshad, Syed Hasan [4 ,5 ]
Relton, Caroline L. [6 ]
Karmaus, Wilfried [1 ]
Zhang, Hongmei [1 ]
机构
[1] Univ Memphis, Sch Publ Hlth, Div Epidemiol Biostat & Environm Hlth, Memphis, TN 38152 USA
[2] Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants, England
[3] Michigan State Univ, Coll Vet Med, E Lansing, MI USA
[4] Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England
[5] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Shrops, England
[6] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England
基金
英国医学研究理事会; 美国国家卫生研究院; 英国生物技术与生命科学研究理事会;
关键词
ALSPAC; Asthma acquisition; DNA methylation; Epigenome-wide; IOWBC; UMBILICAL-CORD BLOOD; CHILDHOOD ASTHMA; ONSET ASTHMA; EXPOSURE; RISK; WIDE; TRANSITION; EXPRESSION; INFANCY; BURDEN;
D O I
10.1111/cea.14091
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background Little is known about the association of newborn DNA methylation (DNAm) with asthma acquisition across adolescence and early adult life. Objective We aim to identify epigenetic biomarkers in newborns for asthma acquisition during adolescence or young adulthood. Methods The Isle of Wight Birth Cohort (IOWBC) (n = 1456) data at ages 10, 18 and 26 years were assessed. To screen cytosine-phosphate-guanine site (CpGs) potentially associated with asthma acquisition, at the genome scale, we examined differentially methylated regions (DMR) using dmrff R package and individual CpG sites using linear regression on such associations. For CpGs that passed screening, we examined their enrichment in biological pathways using their mapping genes and tested their associations with asthma acquisitions using logistic regressions. Findings in IOWBC were tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Results In total, 2636 unique CpGs passed screening, based on which we identified one biological pathway linked to asthma acquisition during adolescence in females (FDR adjusted p-value = .003 in IOWBC). Via logistic regressions, for females, four CpGs were shown to be associated with asthma acquisition during adolescence, and another four CpGs with asthma acquisition in young adulthood (FDR adjusted p-value < .05 in IOWBC) and these eight CpGs were replicated in ALSPAC (all p-values < .05). DNAm at all the identified CpGs was shown to be temporally consistent, and at six of the CpGs was associated with expressions of adjacent or mapping genes in females (all p-values < .05). For males, 622 CpGs were identified in IOWBC (FDR = 0.01), but these were not tested in ALSPAC due to small sample sizes. Conclusion and clinical relevance Eight CpGs on LHX5, IL22RA2, SOX11, CBX4, ACPT, CFAP46, MUC4, and ATP1B2 genes have the potential to serve as candidate epigenetic biomarkers in newborns for asthma acquisition in females during adolescence or young adulthood.
引用
收藏
页码:658 / 669
页数:12
相关论文
共 65 条
[1]   Genetic and observational evidence supports a causal role of sex hormones on the development of asthma [J].
Arathimos, Ryan ;
Granell, Raquel ;
Haycock, Philip ;
Richmond, Rebecca C. ;
Yarmolinsky, James ;
Relton, Caroline L. ;
Tilling, Kate .
THORAX, 2019, 74 (07) :633-642
[2]   Cohort Profile: The Isle Of Wight Whole Population Birth Cohort (IOWBC) [J].
Arshad, S. Hasan ;
Holloway, John W. ;
Karmaus, Wilfried ;
Zhang, Hongmei ;
Ewart, Susan ;
Mansfield, Linda ;
Matthews, Sharon ;
Hodgekiss, Claire ;
Roberts, Graham ;
Kurukulaaratchy, Ramesh .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2018, 47 (04) :1043-+
[3]   Pathophysiological characterization of asthma transitions across adolescence [J].
Arshad, Syed Hasan ;
Raza, Abid ;
Lau, Laurie ;
Bawakid, Khalid ;
Karmaus, Wilfried ;
Zhang, Hongmei ;
Ewart, Susan ;
Patil, Veersh ;
Roberts, Graham ;
Kurukulaaratchy, Ramesh .
RESPIRATORY RESEARCH, 2014, 15
[4]   Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays [J].
Aryee, Martin J. ;
Jaffe, Andrew E. ;
Corrada-Bravo, Hector ;
Ladd-Acosta, Christine ;
Feinberg, Andrew P. ;
Hansen, Kasper D. ;
Irizarry, Rafael A. .
BIOINFORMATICS, 2014, 30 (10) :1363-1369
[5]   Epigenetic Changes in Asthma: Role of DNA CpG Methylation [J].
Bae, Da-Jeong ;
Jun, Ji Ae ;
Chang, Hun Soo ;
Park, Jong Sook ;
Park, Choon-Sik .
TUBERCULOSIS AND RESPIRATORY DISEASES, 2020, 83 (01) :1-13
[6]   Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells [J].
Bafna, S. ;
Kaur, S. ;
Batra, S. K. .
ONCOGENE, 2010, 29 (20) :2893-2904
[7]   DNA methylation of cord blood cell types: Applications for mixed cell birth studies [J].
Bakulski, Kelly M. ;
Feinberg, Jason I. ;
Andrews, Shan V. ;
Yang, Jack ;
Brown, Shannon ;
McKenney, Stephanie L. ;
Witter, Frank ;
Walston, Jeremy ;
Feinberg, Andrew P. ;
Fallin, M. Daniele .
EPIGENETICS, 2016, 11 (05) :354-362
[8]   Increased TGF-β2 in severe asthma with eosinophilia [J].
Balzar, S ;
Chu, HW ;
Silkoff, P ;
Cundall, M ;
Trudeau, JB ;
Strand, M ;
Wenzel, S .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 115 (01) :110-117
[9]   TNF-α in asthma [J].
Berry, Mike ;
Brightling, Christopher ;
Pavord, Ian ;
Wardlaw, A. J. .
CURRENT OPINION IN PHARMACOLOGY, 2007, 7 (03) :279-282
[10]   High density DNA methylation array with single CpG site resolution [J].
Bibikova, Marina ;
Barnes, Bret ;
Tsan, Chan ;
Ho, Vincent ;
Klotzle, Brandy ;
Le, Jennie M. ;
Delano, David ;
Zhang, Lu ;
Schroth, Gary P. ;
Gunderson, Kevin L. ;
Fan, Jian-Bing ;
Shen, Richard .
GENOMICS, 2011, 98 (04) :288-295