1. Role of DNA methylation in the association of lung function with body mass index:a two-step epigenetic Mendelian randomisation study
- Author
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Amaral, A. F. (André F. S.), Imboden, M. (Medea), Wielscher, M. (Matthias), Rezwan, F. I. (Faisal I.), Minelli, C. (Cosetta), Garcia-Aymerich, J. (Judith), Peralta, G. P. (Gabriela P.), Auvinen, J. (Juha), Jeong, A. (Ayoung), Schaffner, E. (Emmanuel), Beckmeyer-Borowko, A. (Anna), Holloway, J. W. (John W.), Jarvelin, M.-R. (Marjo-Riitta), Probst-Hensch, N. M. (Nicole M.), Jarvis, D. L. (Deborah L.), and f. t. (for the ALEC consortium)
- Subjects
DNA methylation ,Effect mediation ,Mendelian randomisation ,Body mass index ,Lung function - Abstract
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 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
- Published
- 2020