The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study

Abstract Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D across phenotypic domains and disease categories, we conducted Mendelian randomization (MR)...

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Autores principales:	Xia Jiang, Tian Ge, Chia-Yen Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d9271eb586f48ba81f29fd73f5c616b
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spelling	oai:doaj.org-article:1d9271eb586f48ba81f29fd73f5c616b2021-12-02T11:46:07ZThe causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study10.1038/s41598-020-80655-w2045-2322https://doaj.org/article/1d9271eb586f48ba81f29fd73f5c616b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80655-whttps://doaj.org/toc/2045-2322Abstract Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D across phenotypic domains and disease categories, we conducted Mendelian randomization (MR) analyses using genetic instruments associated with circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We leveraged genome-wide significant 25(OH)D-associated SNPs (N = 138) from a meta-analysis combining a vitamin D GWAS conducted in 401,460 white British UK Biobank (UKBB) participants and an independent vitamin D GWAS including 42,274 samples of European ancestry, and examined 190 large-scale health-related GWAS spanning a broad spectrum of complex traits, diseases and biomarkers. We applied multiple MR methods to estimate the causal effect of vitamin D while testing and controlling for potential biases from horizontal pleiotropy. Consistent with previous findings, genetically predicted increased 25(OH)D levels significantly decreased the risk of multiple sclerosis (OR = 0.824; 95% CI 0.689–0.986). The protective effect estimate was consistent across different MR methods and four different multiple sclerosis GWAS with varying sample sizes and genotyping platforms. On the contrary, we found limited evidence in support of a causal effect of 25(OH)D on anthropometric traits, obesity, cognitive function, sleep behavior, breast and prostate cancer, and autoimmune, cardiovascular, metabolic, neurological and psychiatric traits and diseases, and blood biomarkers. Our results may inform ongoing and future randomized clinical trials of vitamin D supplementation.Xia JiangTian GeChia-Yen ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xia Jiang Tian Ge Chia-Yen Chen The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
description	Abstract Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D across phenotypic domains and disease categories, we conducted Mendelian randomization (MR) analyses using genetic instruments associated with circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We leveraged genome-wide significant 25(OH)D-associated SNPs (N = 138) from a meta-analysis combining a vitamin D GWAS conducted in 401,460 white British UK Biobank (UKBB) participants and an independent vitamin D GWAS including 42,274 samples of European ancestry, and examined 190 large-scale health-related GWAS spanning a broad spectrum of complex traits, diseases and biomarkers. We applied multiple MR methods to estimate the causal effect of vitamin D while testing and controlling for potential biases from horizontal pleiotropy. Consistent with previous findings, genetically predicted increased 25(OH)D levels significantly decreased the risk of multiple sclerosis (OR = 0.824; 95% CI 0.689–0.986). The protective effect estimate was consistent across different MR methods and four different multiple sclerosis GWAS with varying sample sizes and genotyping platforms. On the contrary, we found limited evidence in support of a causal effect of 25(OH)D on anthropometric traits, obesity, cognitive function, sleep behavior, breast and prostate cancer, and autoimmune, cardiovascular, metabolic, neurological and psychiatric traits and diseases, and blood biomarkers. Our results may inform ongoing and future randomized clinical trials of vitamin D supplementation.
format	article
author	Xia Jiang Tian Ge Chia-Yen Chen
author_facet	Xia Jiang Tian Ge Chia-Yen Chen
author_sort	Xia Jiang
title	The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
title_short	The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
title_full	The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
title_fullStr	The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
title_full_unstemmed	The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
title_sort	causal role of circulating vitamin d concentrations in human complex traits and diseases: a large-scale mendelian randomization study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1d9271eb586f48ba81f29fd73f5c616b
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The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study

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