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Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study
BACKGROUND: Vitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation. METHODS: In this short report, we leveraged genetic variants which differe...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359699/ https://www.ncbi.nlm.nih.gov/pubmed/35938910 http://dx.doi.org/10.7554/eLife.79798 |
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author | Richardson, Tom G Power, Grace M Davey Smith, George |
author_facet | Richardson, Tom G Power, Grace M Davey Smith, George |
author_sort | Richardson, Tom G |
collection | PubMed |
description | BACKGROUND: Vitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation. METHODS: In this short report, we leveraged genetic variants which differentially influence body size during childhood and adulthood within a multivariable Mendelian randomization (MR) framework, allowing us to separate the genetically predicted effects of adiposity at these two timepoints in the lifecourse. RESULTS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), there was strong evidence that higher childhood body size has a direct effect on lower vitamin D levels in early life (mean age: 9.9 years, range = 8.9–11.5 years) after accounting for the effect of the adult body size genetic score (beta = −0.32, 95% CI = −0.54 to –0.10, p=0.004). Conversely, we found evidence that the effect of childhood body size on vitamin D levels in midlife (mean age: 56.5 years, range = 40–69 years) is putatively mediated along the causal pathway involving adulthood adiposity (beta = −0.17, 95% CI = −0.21 to –0.13, p=4.6 × 10(-17)). CONCLUSIONS: Our findings have important implications in terms of the causal influence of vitamin D deficiency on disease risk. Furthermore, they serve as a compelling proof of concept that the timepoints across the lifecourse at which exposures and outcomes are measured can meaningfully impact overall conclusions drawn by MR studies. FUNDING: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1). |
format | Online Article Text |
id | pubmed-9359699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-93596992022-08-10 Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study Richardson, Tom G Power, Grace M Davey Smith, George eLife Epidemiology and Global Health BACKGROUND: Vitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation. METHODS: In this short report, we leveraged genetic variants which differentially influence body size during childhood and adulthood within a multivariable Mendelian randomization (MR) framework, allowing us to separate the genetically predicted effects of adiposity at these two timepoints in the lifecourse. RESULTS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), there was strong evidence that higher childhood body size has a direct effect on lower vitamin D levels in early life (mean age: 9.9 years, range = 8.9–11.5 years) after accounting for the effect of the adult body size genetic score (beta = −0.32, 95% CI = −0.54 to –0.10, p=0.004). Conversely, we found evidence that the effect of childhood body size on vitamin D levels in midlife (mean age: 56.5 years, range = 40–69 years) is putatively mediated along the causal pathway involving adulthood adiposity (beta = −0.17, 95% CI = −0.21 to –0.13, p=4.6 × 10(-17)). CONCLUSIONS: Our findings have important implications in terms of the causal influence of vitamin D deficiency on disease risk. Furthermore, they serve as a compelling proof of concept that the timepoints across the lifecourse at which exposures and outcomes are measured can meaningfully impact overall conclusions drawn by MR studies. FUNDING: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1). eLife Sciences Publications, Ltd 2022-08-08 /pmc/articles/PMC9359699/ /pubmed/35938910 http://dx.doi.org/10.7554/eLife.79798 Text en © 2022, Richardson et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Epidemiology and Global Health Richardson, Tom G Power, Grace M Davey Smith, George Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study |
title | Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study |
title_full | Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study |
title_fullStr | Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study |
title_full_unstemmed | Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study |
title_short | Adiposity may confound the association between vitamin D and disease risk – a lifecourse Mendelian randomization study |
title_sort | adiposity may confound the association between vitamin d and disease risk – a lifecourse mendelian randomization study |
topic | Epidemiology and Global Health |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359699/ https://www.ncbi.nlm.nih.gov/pubmed/35938910 http://dx.doi.org/10.7554/eLife.79798 |
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