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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Main Authors: Xia Jiang, Tian Ge, Chia-Yen Chen
Format: Article
Language:English
Published: Nature Portfolio 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-80655-w
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author Xia Jiang
Tian Ge
Chia-Yen Chen
author_facet Xia Jiang
Tian Ge
Chia-Yen Chen
author_sort Xia Jiang
collection DOAJ
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.
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spelling doaj.art-1d9271eb586f48ba81f29fd73f5c616b2022-12-21T19:31:09ZengNature PortfolioScientific Reports2045-23222021-01-0111111010.1038/s41598-020-80655-wThe causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization studyXia Jiang0Tian Ge1Chia-Yen Chen2West China School of Public Health and West China Fourth Hospital, Sichuan UniversityPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General HospitalPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General HospitalAbstract 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.https://doi.org/10.1038/s41598-020-80655-w
spellingShingle 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
Scientific Reports
title 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_short 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
url https://doi.org/10.1038/s41598-020-80655-w
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