Cargando…

Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases

BACKGROUND: Circulating vitamin D has been associated with multiple clinical diseases in observational studies, but the association was inconsistent due to the presence of confounders. We conducted a bidirectional Mendelian randomization (MR) study to explore the healthy atlas of vitamin D in many c...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Jin-jian, Zhang, Xiao-bin, Tong, Wen-tao, Ying, Teng, Liu, Ke-qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095159/
https://www.ncbi.nlm.nih.gov/pubmed/37063319
http://dx.doi.org/10.3389/fnut.2023.1108477
_version_ 1785024016066543616
author Xu, Jin-jian
Zhang, Xiao-bin
Tong, Wen-tao
Ying, Teng
Liu, Ke-qi
author_facet Xu, Jin-jian
Zhang, Xiao-bin
Tong, Wen-tao
Ying, Teng
Liu, Ke-qi
author_sort Xu, Jin-jian
collection PubMed
description BACKGROUND: Circulating vitamin D has been associated with multiple clinical diseases in observational studies, but the association was inconsistent due to the presence of confounders. We conducted a bidirectional Mendelian randomization (MR) study to explore the healthy atlas of vitamin D in many clinical traits and evaluate their causal association. METHODS: Based on a large-scale genome-wide association study (GWAS), the single nucleotide polymorphism (SNPs) instruments of circulating 25-hydroxyvitamin D (25OHD) from 443,734 Europeans and the corresponding effects of 10 clinical diseases and 42 clinical traits in the European population were recruited to conduct a bidirectional two-sample Mendelian randomization study. Under the network of Mendelian randomization analysis, inverse-variance weighting (IVW), weighted median, weighted mode, and Mendelian randomization (MR)–Egger regression were performed to explore the causal effects and pleiotropy. Mendelian randomization pleiotropy RESidual Sum and Outlier (MR-PRESSO) was conducted to uncover and exclude pleiotropic SNPs. RESULTS: The results revealed that genetically decreased vitamin D was inversely related to the estimated BMD (β = −0.029 g/cm(2), p = 0.027), TC (β = −0.269 mmol/L, p = 0.006), TG (β = −0.208 mmol/L, p = 0.002), and pulse pressure (β = −0.241 mmHg, p = 0.043), while positively associated with lymphocyte count (β = 0.037%, p = 0.015). The results did not reveal any causal association of vitamin D with clinical diseases. On the contrary, genetically protected CKD was significantly associated with increased vitamin D (β = 0.056, p = 2.361 × 10(−26)). CONCLUSION: The putative causal effects of circulating vitamin D on estimated bone mass, plasma triglyceride, and total cholesterol were uncovered, but not on clinical diseases. Vitamin D may be linked to clinical disease by affecting health-related metabolic markers.
format Online
Article
Text
id pubmed-10095159
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-100951592023-04-13 Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases Xu, Jin-jian Zhang, Xiao-bin Tong, Wen-tao Ying, Teng Liu, Ke-qi Front Nutr Nutrition BACKGROUND: Circulating vitamin D has been associated with multiple clinical diseases in observational studies, but the association was inconsistent due to the presence of confounders. We conducted a bidirectional Mendelian randomization (MR) study to explore the healthy atlas of vitamin D in many clinical traits and evaluate their causal association. METHODS: Based on a large-scale genome-wide association study (GWAS), the single nucleotide polymorphism (SNPs) instruments of circulating 25-hydroxyvitamin D (25OHD) from 443,734 Europeans and the corresponding effects of 10 clinical diseases and 42 clinical traits in the European population were recruited to conduct a bidirectional two-sample Mendelian randomization study. Under the network of Mendelian randomization analysis, inverse-variance weighting (IVW), weighted median, weighted mode, and Mendelian randomization (MR)–Egger regression were performed to explore the causal effects and pleiotropy. Mendelian randomization pleiotropy RESidual Sum and Outlier (MR-PRESSO) was conducted to uncover and exclude pleiotropic SNPs. RESULTS: The results revealed that genetically decreased vitamin D was inversely related to the estimated BMD (β = −0.029 g/cm(2), p = 0.027), TC (β = −0.269 mmol/L, p = 0.006), TG (β = −0.208 mmol/L, p = 0.002), and pulse pressure (β = −0.241 mmHg, p = 0.043), while positively associated with lymphocyte count (β = 0.037%, p = 0.015). The results did not reveal any causal association of vitamin D with clinical diseases. On the contrary, genetically protected CKD was significantly associated with increased vitamin D (β = 0.056, p = 2.361 × 10(−26)). CONCLUSION: The putative causal effects of circulating vitamin D on estimated bone mass, plasma triglyceride, and total cholesterol were uncovered, but not on clinical diseases. Vitamin D may be linked to clinical disease by affecting health-related metabolic markers. Frontiers Media S.A. 2023-03-29 /pmc/articles/PMC10095159/ /pubmed/37063319 http://dx.doi.org/10.3389/fnut.2023.1108477 Text en Copyright © 2023 Xu, Zhang, Tong, Ying and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Xu, Jin-jian
Zhang, Xiao-bin
Tong, Wen-tao
Ying, Teng
Liu, Ke-qi
Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases
title Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases
title_full Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases
title_fullStr Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases
title_full_unstemmed Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases
title_short Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases
title_sort phenome-wide mendelian randomization study evaluating the association of circulating vitamin d with complex diseases
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095159/
https://www.ncbi.nlm.nih.gov/pubmed/37063319
http://dx.doi.org/10.3389/fnut.2023.1108477
work_keys_str_mv AT xujinjian phenomewidemendelianrandomizationstudyevaluatingtheassociationofcirculatingvitamindwithcomplexdiseases
AT zhangxiaobin phenomewidemendelianrandomizationstudyevaluatingtheassociationofcirculatingvitamindwithcomplexdiseases
AT tongwentao phenomewidemendelianrandomizationstudyevaluatingtheassociationofcirculatingvitamindwithcomplexdiseases
AT yingteng phenomewidemendelianrandomizationstudyevaluatingtheassociationofcirculatingvitamindwithcomplexdiseases
AT liukeqi phenomewidemendelianrandomizationstudyevaluatingtheassociationofcirculatingvitamindwithcomplexdiseases