Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study
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 E...
Published in: | BMC Pulmonary Medicine |
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BioMed Central
2020
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Online Access: | http://hdl.handle.net/10044/1/80902 https://doi.org/10.1186/s12890-020-01212-9 |
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ftimperialcol:oai:spiral.imperial.ac.uk:10044/1/80902 |
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Open Polar |
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Imperial College London: Spiral |
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unknown |
topic |
Science & Technology Life Sciences & Biomedicine Respiratory System Body mass index Lung function DNA methylation Effect mediation Mendelian randomisation EPIGENOME-WIDE ASSOCIATION MULTIPLE GENETIC-VARIANTS CAUSAL ROLE INSTRUMENTS OBESITY BLOOD ALEC consortium 1102 Cardiorespiratory Medicine and Haematology |
spellingShingle |
Science & Technology Life Sciences & Biomedicine Respiratory System Body mass index Lung function DNA methylation Effect mediation Mendelian randomisation EPIGENOME-WIDE ASSOCIATION MULTIPLE GENETIC-VARIANTS CAUSAL ROLE INSTRUMENTS OBESITY BLOOD ALEC consortium 1102 Cardiorespiratory Medicine and Haematology Amaral, A Imboden, M Wielscher, M Rezwan, FI Minelli, C Garcia-Aymerich, J Peralta, GP Auvinen, J Jeong, A Schaffner, E Beckmeyer-Borowko, A Holloway, JW Jarvelin, M-R Probst-Hensch, NM Jarvis, DL Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study |
topic_facet |
Science & Technology Life Sciences & Biomedicine Respiratory System Body mass index Lung function DNA methylation Effect mediation Mendelian randomisation EPIGENOME-WIDE ASSOCIATION MULTIPLE GENETIC-VARIANTS CAUSAL ROLE INSTRUMENTS OBESITY BLOOD ALEC consortium 1102 Cardiorespiratory Medicine and Haematology |
description |
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 < 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. |
author2 |
Commission of the European Communities Medical Research Council (MRC) |
format |
Article in Journal/Newspaper |
author |
Amaral, A Imboden, M Wielscher, M Rezwan, FI Minelli, C Garcia-Aymerich, J Peralta, GP Auvinen, J Jeong, A Schaffner, E Beckmeyer-Borowko, A Holloway, JW Jarvelin, M-R Probst-Hensch, NM Jarvis, DL |
author_facet |
Amaral, A Imboden, M Wielscher, M Rezwan, FI Minelli, C Garcia-Aymerich, J Peralta, GP Auvinen, J Jeong, A Schaffner, E Beckmeyer-Borowko, A Holloway, JW Jarvelin, M-R Probst-Hensch, NM Jarvis, DL |
author_sort |
Amaral, A |
title |
Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study |
title_short |
Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study |
title_full |
Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study |
title_fullStr |
Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study |
title_full_unstemmed |
Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study |
title_sort |
role of dna methylation in the association of lung function with body mass index: a two-step epigenetic mendelian randomisation study |
publisher |
BioMed Central |
publishDate |
2020 |
url |
http://hdl.handle.net/10044/1/80902 https://doi.org/10.1186/s12890-020-01212-9 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
8 1 |
op_relation |
BMC Pulmonary Medicine 1471-2466 http://hdl.handle.net/10044/1/80902 doi:10.1186/s12890-020-01212-9 633212 G1002319 |
op_rights |
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. http://creativecommons.org/licenses/by/4.0 |
op_rightsnorm |
CC0 PDM CC-BY |
op_doi |
https://doi.org/10.1186/s12890-020-01212-9 |
container_title |
BMC Pulmonary Medicine |
container_volume |
20 |
container_issue |
1 |
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ftimperialcol:oai:spiral.imperial.ac.uk:10044/1/80902 2023-05-15T17:42:57+02:00 Role of DNA methylation in the association of lung function with body mass index: A two-step epigenetic Mendelian randomisation study Amaral, A Imboden, M Wielscher, M Rezwan, FI Minelli, C Garcia-Aymerich, J Peralta, GP Auvinen, J Jeong, A Schaffner, E Beckmeyer-Borowko, A Holloway, JW Jarvelin, M-R Probst-Hensch, NM Jarvis, DL Commission of the European Communities Medical Research Council (MRC) 2020-06-09 http://hdl.handle.net/10044/1/80902 https://doi.org/10.1186/s12890-020-01212-9 unknown BioMed Central BMC Pulmonary Medicine 1471-2466 http://hdl.handle.net/10044/1/80902 doi:10.1186/s12890-020-01212-9 633212 G1002319 © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. http://creativecommons.org/licenses/by/4.0 CC0 PDM CC-BY 8 1 Science & Technology Life Sciences & Biomedicine Respiratory System Body mass index Lung function DNA methylation Effect mediation Mendelian randomisation EPIGENOME-WIDE ASSOCIATION MULTIPLE GENETIC-VARIANTS CAUSAL ROLE INSTRUMENTS OBESITY BLOOD ALEC consortium 1102 Cardiorespiratory Medicine and Haematology Journal Article 2020 ftimperialcol https://doi.org/10.1186/s12890-020-01212-9 2020-07-30T22:38:25Z 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 < 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. Article in Journal/Newspaper Northern Finland Imperial College London: Spiral BMC Pulmonary Medicine 20 1 |