Background: Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation.
Methods: We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV, FVC, and FEV/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2.
Results: In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs.
Conclusions: To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.
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http://dx.doi.org/10.1186/s12890-020-01212-9 | DOI Listing |
Biol Sex Differ
December 2024
State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Background: DNA methylation (DNAm) influences both sex differences and cancer development, yet the mechanisms connecting these factors remain unclear.
Methods: Utilizing data from The Cancer Genome Atlas, we conducted a comprehensive analysis of sex-related DNAm effects in nine non-reproductive cancers, compared to paired normal adjacent tissues (NATs), and validated the results using independent datasets. First, we assessed the extent of sex differential DNAm between cancers and NATs to explore how sex-related DNAm differences change in cancerous tissues.
BMC Genomics
December 2024
Grapevine Improvement, Bragato Research Institute, Lincoln, New Zealand.
Nanopore sequencing enables detection of DNA methylation at the same time as identification of canonical sequence. A recent study validated low-pass nanopore sequencing to accurately estimate global methylation levels in vertebrates with sequencing coverage as low as 0.01x.
View Article and Find Full Text PDFBMC Genomics
December 2024
Department of Biological Sciences, Seoul National University, Seoul, Korea.
Background: Plants possess a high potential for somatic cell reprogramming, enabling the transition from differentiated tissue to pluripotent callus, followed by the formation of de novo shoots during plant regeneration. Despite extensive studies on the molecular network and key genetic factors involved in this process, the underlying epigenetic landscape remains incompletely understood.
Results: Here, we explored the dynamics of the methylome and transcriptome during the two-step plant regeneration process.
Discov Oncol
December 2024
Department of Gastroenterology, Second Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, China.
Background: ZBTB11 is a putative transcription factor with an N-terminal BTB domain and tandem C-terminal zinc finger motifs. Recent studies have suggested a potential role for ZBTB11 in tumorigenesis. However, the biological significance of ZBTB11 in different cancer types remains uncertain.
View Article and Find Full Text PDFJ Mol Evol
December 2024
Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
The time of integration of germline-targeting Long Terminal Repeat (LTR) retroposons, such as endogenous retroviruses (ERVs), can be estimated by assessing the nucleotide divergence between the LTR sequences flanking the viral genes. Due to the viral replication mechanism, both LTRs are identical at the moment of integration, when the provirus becomes part of the host genome. After that time, proviral sequences evolve within the host DNA.
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