Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved]
Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wellcome
2021-07-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/5-281/v2 |
| _version_ | 1819144889418383360 |
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| author | Serena A. Dodhia Nicola X. West Steven J. Thomas Nicholas J. Timpson Ingegerd Johansson Pernilla Lif Holgerson Tom Dudding Simon Haworth |
| author_facet | Serena A. Dodhia Nicola X. West Steven J. Thomas Nicholas J. Timpson Ingegerd Johansson Pernilla Lif Holgerson Tom Dudding Simon Haworth |
| author_sort | Serena A. Dodhia |
| collection | DOAJ |
| description | Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome. Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years). Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68) Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries. |
| first_indexed | 2024-12-22T12:49:18Z |
| format | Article |
| id | doaj.art-84054ef940804589936d62db69384e32 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-22T12:49:18Z |
| publishDate | 2021-07-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-84054ef940804589936d62db69384e322022-12-21T18:25:15ZengWellcomeWellcome Open Research2398-502X2021-07-01510.12688/wellcomeopenres.16369.218849Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved]Serena A. Dodhia0Nicola X. West1Steven J. Thomas2Nicholas J. Timpson3Ingegerd Johansson4Pernilla Lif Holgerson5Tom Dudding6Simon Haworth7Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UKBristol Dental School, University of Bristol, Bristol, BS1 2LY, UKBristol Dental School, University of Bristol, Bristol, BS1 2LY, UKMedical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 2BN, UKDepartment of Odontology, Section of Cariology, Umea University, Umeå, SwedenDepartment of Odontology, Section of Pedodontics, Umea University, Umeå, SwedenBristol Dental School, University of Bristol, Bristol, BS1 2LY, UKBristol Dental School, University of Bristol, Bristol, BS1 2LY, UKBackground: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome. Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years). Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68) Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries.https://wellcomeopenresearch.org/articles/5-281/v2 |
| spellingShingle | Serena A. Dodhia Nicola X. West Steven J. Thomas Nicholas J. Timpson Ingegerd Johansson Pernilla Lif Holgerson Tom Dudding Simon Haworth Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved] Wellcome Open Research |
| title | Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved] |
| title_full | Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved] |
| title_fullStr | Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved] |
| title_full_unstemmed | Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved] |
| title_short | Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach [version 2; peer review: 2 approved] |
| title_sort | examining the causal association between 25 hydroxyvitamin d and caries in children and adults a two sample mendelian randomization approach version 2 peer review 2 approved |
| url | https://wellcomeopenresearch.org/articles/5-281/v2 |
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