机构：[1]West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.[2]Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.[3]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, 17165 Stockholm, Sweden.[4]Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.[5]Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.[6]Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.[7]Biogen, Cambridge, MA 02142, USA
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.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
最新[2023]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
第一作者：
第一作者机构：[1]West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.[2]Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.[3]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, 17165 Stockholm, Sweden.
通讯作者：
通讯机构：[1]West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.[2]Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.[3]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, 17165 Stockholm, Sweden.[4]Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.[5]Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.[6]Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.[7]Biogen, Cambridge, MA 02142, USA
推荐引用方式(GB/T 7714)：
Jiang Xia,Ge Tian,Chen Chia-Yen.The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study.[J].Scientific reports.2021,11(1):184.doi:10.1038/s41598-020-80655-w.
APA：
Jiang Xia,Ge Tian&Chen Chia-Yen.(2021).The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study..Scientific reports,11,(1)
MLA：
Jiang Xia,et al."The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study.".Scientific reports 11..1(2021):184
