Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study

Simple item page
dc.contributor.authorAmaral, André F. S.
dc.contributor.authorImboden, Medea
dc.contributor.authorWielscher, Matthias
dc.contributor.authorRezwan, Faisal I.
dc.contributor.authorMinelli, Cosetta
dc.contributor.authorGarcia-Aymerich, Judith
dc.contributor.authorPeralta, Gabriela P.
dc.contributor.authorAuvinen, Juha
dc.contributor.authorJeong, Ayoung
dc.contributor.authorSchaffner, Emmanuel
dc.contributor.authorBeckmeyer-Borowko, Anna
dc.contributor.authorHolloway, John W.
dc.contributor.authorJarvelin, Marjo-Riitta
dc.contributor.authorProbst-Hensch, Nicole
dc.contributor.authorJarvis, Deborah L.
dc.date.accessioned2021-02-15T12:48:07Z
dc.date.available2021-02-15T12:48:07Z
dc.date.issued2020-06-16
dc.description.abstractBackground 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 FEV1, FVC, and FEV1/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.en_UK
dc.identifier.citationAmaral AFS, Imboden M, Wielscher M, et al., (2020) Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study. BMC Pulmonary Medicine, Volume 20, Issue 1, 2020, Article No. 171en_UK
dc.identifier.issn1471-2466
dc.identifier.urihttps://doi.org/10.1186/s12890-020-01212-9
dc.identifier.urihttp://dspace.lib.cranfield.ac.uk/handle/1826/16342
dc.language.isoenen_UK
dc.publisherBioMed Centralen_UK
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBody mass indexen_UK
dc.subjectLung functionen_UK
dc.subjectDNA methylationen_UK
dc.subjectEffect mediationen_UK
dc.subjectMendelian randomisationen_UK
dc.titleRole of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation studyen_UK
dc.typeArticleen_UK

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
DNA_methylation-lung_function-2021.pdf
Size:
593.29 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.63 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Staff publications (SWEE)