Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment
BACKGROUND: Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors. METHODS: We performed three analys...
Published in: | Genome Medicine |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
BioMed Central
2021
|
Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215837/ http://www.ncbi.nlm.nih.gov/pubmed/34154662 https://doi.org/10.1186/s13073-021-00914-x |
id |
ftpubmed:oai:pubmedcentral.nih.gov:8215837 |
---|---|
record_format |
openpolar |
institution |
Open Polar |
collection |
PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Research |
spellingShingle |
Research Wielscher, Matthias Amaral, Andre F. S. van der Plaat, Diana Wain, Louise V. Sebert, Sylvain Mosen-Ansorena, David Auvinen, Juha Herzig, Karl-Heinz Dehghan, Abbas Jarvis, Debbie L. Jarvelin, Marjo-Riitta Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
topic_facet |
Research |
description |
BACKGROUND: Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors. METHODS: We performed three analyses: (1) cardio-metabolic health to lung function association tests in Northern Finland Birth cohort 1966, (2) cross-trait linkage disequilibrium score regression (LDSC) to compare genetic backgrounds and (3) Mendelian randomisation (MR) analysis to assess the causal effect of cardio-metabolic traits and disease on lung function, and vice versa (bidirectional MR). Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies (N > 82,000). RESULTS: We observed a negative genetic correlation between lung function and cardio-metabolic traits and diseases. In Mendelian Randomisation analysis (MR), we found associations between type 2 diabetes (T2D) instruments and forced vital capacity (FVC) as well as FEV1/FVC. Body mass index (BMI) instruments were associated to all lung function traits and C-reactive protein (CRP) instruments to FVC. These genetic associations provide evidence for a causal effect of cardio-metabolic traits on lung function. Multivariable MR suggested independence of these causal effects from other tested cardio-metabolic traits and diseases. Analysis of lung function specific SNPs revealed a potential causal effect of FEV1/FVC on blood pressure. CONCLUSIONS: The present study overcomes many limitations of observational studies by using Mendelian Randomisation. We provide evidence for an independent causal effect of T2D, CRP and BMI on lung function with some of the T2D effect on lung function being attributed to inflammatory mechanisms. Furthermore, this analysis suggests a potential causal effect of FEV1/FVC on blood pressure. Our detailed analysis of the interplay between cardio-metabolic traits and impaired lung function provides the ... |
format |
Text |
author |
Wielscher, Matthias Amaral, Andre F. S. van der Plaat, Diana Wain, Louise V. Sebert, Sylvain Mosen-Ansorena, David Auvinen, Juha Herzig, Karl-Heinz Dehghan, Abbas Jarvis, Debbie L. Jarvelin, Marjo-Riitta |
author_facet |
Wielscher, Matthias Amaral, Andre F. S. van der Plaat, Diana Wain, Louise V. Sebert, Sylvain Mosen-Ansorena, David Auvinen, Juha Herzig, Karl-Heinz Dehghan, Abbas Jarvis, Debbie L. Jarvelin, Marjo-Riitta |
author_sort |
Wielscher, Matthias |
title |
Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
title_short |
Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
title_full |
Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
title_fullStr |
Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
title_full_unstemmed |
Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
title_sort |
genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment |
publisher |
BioMed Central |
publishDate |
2021 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215837/ http://www.ncbi.nlm.nih.gov/pubmed/34154662 https://doi.org/10.1186/s13073-021-00914-x |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
Genome Med |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215837/ http://www.ncbi.nlm.nih.gov/pubmed/34154662 http://dx.doi.org/10.1186/s13073-021-00914-x |
op_rights |
© The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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. |
op_rightsnorm |
CC0 PDM CC-BY |
op_doi |
https://doi.org/10.1186/s13073-021-00914-x |
container_title |
Genome Medicine |
container_volume |
13 |
container_issue |
1 |
_version_ |
1766144691741392896 |
spelling |
ftpubmed:oai:pubmedcentral.nih.gov:8215837 2023-05-15T17:42:46+02:00 Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment Wielscher, Matthias Amaral, Andre F. S. van der Plaat, Diana Wain, Louise V. Sebert, Sylvain Mosen-Ansorena, David Auvinen, Juha Herzig, Karl-Heinz Dehghan, Abbas Jarvis, Debbie L. Jarvelin, Marjo-Riitta 2021-06-21 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215837/ http://www.ncbi.nlm.nih.gov/pubmed/34154662 https://doi.org/10.1186/s13073-021-00914-x en eng BioMed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215837/ http://www.ncbi.nlm.nih.gov/pubmed/34154662 http://dx.doi.org/10.1186/s13073-021-00914-x © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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. CC0 PDM CC-BY Genome Med Research Text 2021 ftpubmed https://doi.org/10.1186/s13073-021-00914-x 2021-06-27T00:36:26Z BACKGROUND: Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors. METHODS: We performed three analyses: (1) cardio-metabolic health to lung function association tests in Northern Finland Birth cohort 1966, (2) cross-trait linkage disequilibrium score regression (LDSC) to compare genetic backgrounds and (3) Mendelian randomisation (MR) analysis to assess the causal effect of cardio-metabolic traits and disease on lung function, and vice versa (bidirectional MR). Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies (N > 82,000). RESULTS: We observed a negative genetic correlation between lung function and cardio-metabolic traits and diseases. In Mendelian Randomisation analysis (MR), we found associations between type 2 diabetes (T2D) instruments and forced vital capacity (FVC) as well as FEV1/FVC. Body mass index (BMI) instruments were associated to all lung function traits and C-reactive protein (CRP) instruments to FVC. These genetic associations provide evidence for a causal effect of cardio-metabolic traits on lung function. Multivariable MR suggested independence of these causal effects from other tested cardio-metabolic traits and diseases. Analysis of lung function specific SNPs revealed a potential causal effect of FEV1/FVC on blood pressure. CONCLUSIONS: The present study overcomes many limitations of observational studies by using Mendelian Randomisation. We provide evidence for an independent causal effect of T2D, CRP and BMI on lung function with some of the T2D effect on lung function being attributed to inflammatory mechanisms. Furthermore, this analysis suggests a potential causal effect of FEV1/FVC on blood pressure. Our detailed analysis of the interplay between cardio-metabolic traits and impaired lung function provides the ... Text Northern Finland PubMed Central (PMC) Genome Medicine 13 1 |