The association of cigarette smoking with DNA methylation and gene expression in human tissue samples.

Autor:	Li JL; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA; Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL 60637, USA., Jain N; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA; Committee on Genetics, Genomics, Systems Biology, University of Chicago, Chicago, IL 60637, USA., Tamayo LI; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Tong L; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Jasmine F; Institute for Population and Precision Health (IPPH), Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA., Kibriya MG; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Demanelis K; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA., Oliva M; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA; Genomics Research Center, AbbVie, North Chicago, IL 60064, USA., Chen LS; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Pierce BL; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA; Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, USA. Electronic address: brandonpierce@uchicago.edu.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2024 Apr 04; Vol. 111 (4), pp. 636-653. Date of Electronic Publication: 2024 Mar 14.
DOI:	10.1016/j.ajhg.2024.02.012
Abstrakt:	Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle). We identified 6,350 smoking-associated CpGs in lung tissue (n = 212) and 2,735 in colon tissue (n = 210), most not reported previously. For all 7 other tissue types (sample sizes 38-153), no clear associations were observed (false discovery rate 0.05), but some tissues showed enrichment for smoking-associated CpGs reported previously. For 1,646 loci (in lung) and 22 (in colon), smoking was associated with both DNAm and local gene expression. For loci detected in both lung and colon (e.g., AHRR, CYP1B1, CYP1A1), top CpGs often differed between tissues, but similar clusters of hyper- or hypomethylated CpGs were observed, with hypomethylation at regulatory elements corresponding to increased expression. For lung tissue, 17 hallmark gene sets were enriched for smoking-associated CpGs, including xenobiotic- and cancer-related gene sets. At least four smoking-associated regions in lung were impacted by lung methylation quantitative trait loci (QTLs) that co-localize with genome-wide association study (GWAS) signals for lung function (FEV1/FVC), suggesting epigenetic alterations can mediate the effects of smoking on lung health. Our multi-tissue approach has identified smoking-associated regions in disease-relevant tissues, including effects that are shared across tissue types. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu