Fathers' preconception smoking and offspring DNA methylation.

IF 5.7 2区 医学 Q1 Medicine
Negusse Tadesse Kitaba, Gerd Toril Mørkve Knudsen, Ane Johannessen, Faisal I Rezwan, Andrei Malinovschi, Anna Oudin, Bryndis Benediktsdottir, David Martino, Francisco Javier Callejas González, Leopoldo Palacios Gómez, Mathias Holm, Nils Oskar Jõgi, Shyamali C Dharmage, Svein Magne Skulstad, Sarah H Watkins, Matthew Suderman, Francisco Gómez-Real, Vivi Schlünssen, Cecilie Svanes, John W Holloway
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引用次数: 0

Abstract

Background: Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking.

Methods: We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7-50 years) on father's any preconception smoking (n = 875 offspring) and father's pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father's smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure.

Results: Father's smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father's smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure.

Conclusion: Father's preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.

Abstract Image

Abstract Image

Abstract Image

父亲的先入为主吸烟和后代DNA甲基化。
背景:实验研究表明,暴露可能通过特异性通过雄性生殖细胞传播的表观遗传变化影响几代人的呼吸健康。然而,对人类的研究是有限的。我们的目的是鉴定与父亲先入为主吸烟相关的后代的表观遗传学标记。方法:我们在RHINESSA队列(7-50岁)中对父亲的任何先入为主吸烟(n = 875个后代)和父亲青春期开始吸烟 结果:父亲吸烟开始先入为主与后代血液DNA在两个胞嘧啶磷酸鸟嘌呤位点(CpGs)的甲基化有关(错误发现率(FDR)) 结论:父亲的先入为主的吸烟,特别是在青春期,与后代DNA甲基化有关,这提供了表观遗传学机制的证据,这些机制可能是流行病学观察的基础,即青春期父亲吸烟会增加后代患哮喘、肺功能低下和肥胖的风险。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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