{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:47Z","timestamp":1785413627796,"version":"3.56.0"},"reference-count":28,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00011\/1"],"award-info":[{"award-number":["MC_UU_00011\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council and Wellcome","doi-asserted-by":"publisher","award":["217065\/Z\/19\/Z"],"award-info":[{"award-number":["217065\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,7,22]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      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\u201311.5 years) after accounting for the effect of the adult body size genetic score (beta = \u22120.32, 95% CI = \u22120.54 to \u20130.10, 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\u201369 years) is putatively mediated along the causal pathway involving adulthood adiposity (beta = \u22120.17, 95% CI = \u22120.21 to \u20130.13, p=4.6 \u00d7 10\n                      <jats:sup>-17<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.79798","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T05:15:10Z","timestamp":1658726110000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.79798","source":"Crossref","is-referenced-by-count":15,"title":["Adiposity may confound the association between vitamin D and disease risk \u2013 a lifecourse Mendelian randomization study"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7918-2040","authenticated-orcid":true,"given":"Tom G","family":"Richardson","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0524sp257","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-7728","authenticated-orcid":true,"given":"Grace M","family":"Power","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0524sp257","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-8314","authenticated-orcid":true,"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0524sp257","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41574-021-00593-z","article-title":"The health effects of vitamin D supplementation: evidence from human studies","volume":"18","author":"Bouillon","year":"2022","journal-title":"Nature Reviews. 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