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Phenome-wide Mendelian-randomization study of genetically determined vitamin D on multiple health outcomes using the UK Biobank study

Published on Oct 1, 2019in International Journal of Epidemiology7.339
· DOI :10.1093/ije/dyz182
Xiangrui Meng5
Estimated H-index: 5
(Edin.: University of Edinburgh),
Xue Li8
Estimated H-index: 8
(Edin.: University of Edinburgh)
+ 14 AuthorsEvropi Theodoratou40
Estimated H-index: 40
(Edin.: University of Edinburgh)
Abstract
  • References (34)
  • Citations (2)
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2018
1 Author (Xiangrui Meng)
20197.55eLife
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References34
Newest
#1Karl MichaëlssonH-Index: 61
#2Håkan MelhusH-Index: 35
Last. Susanna C. LarssonH-Index: 61
view all 3 authors...
Whether vitamin D insufficiency is a contributing cause of depression remains unclear. We assessed whether serum 25-hydroxyvitamin D (S-25OHD) concentrations, the clinical marker of vitamin D status, were associated with major depression using Mendelian randomization. We used summary statistics data for six single-nucleotide polymorphisms significantly associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) consorti...
7 CitationsSource
#1Katerina Trajanoska (EUR: Erasmus University Rotterdam)H-Index: 9
#2John A. Morris (McGill University)H-Index: 10
Last. Fernando Rivadeneira (EUR: Erasmus University Rotterdam)H-Index: 117
view all 9 authors...
Objectives To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. Design Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. Setting 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. Participants A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture case...
35 CitationsSource
Most trials of vitamin D supplementation have shown no benefits on bone density (BMD), though severe vitamin D deficiency causes osteomalacia which is associated with profound BMD deficits. Recently, the ViDA-BMD study from New Zealand demonstrated a threshold of baseline 25-hydroxyvitamin D (30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now re-examined data from a similar trial in Aberdeen to determine whether a baseline 25-hydroxyvitamin D threshold of 30 nmol/L is ...
19 CitationsSource
#1Xue Li (Edin.: University of Edinburgh)H-Index: 8
#2Xiangrui Meng (Edin.: University of Edinburgh)H-Index: 5
Last. Evropi TheodoratouH-Index: 9
view all 16 authors...
Objectives We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank. Methods We performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelian randomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysi...
12 CitationsSource
#1Xia Jiang (KI: Karolinska Institutet)H-Index: 6
#2Paul F. O'Reilly ('KCL': King's College London)H-Index: 39
Last. Douglas P. Kiel (MIT: Massachusetts Institute of Technology)H-Index: 98
view all 104 authors...
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC...
62 CitationsSource
#1Jia-Guo ZhaoH-Index: 3
#2Xian-Tie ZengH-Index: 3
Last. Lin LiuH-Index: 2
view all 4 authors...
Importance The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults. Objective To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in ...
93 CitationsSource
#1Ian R. Reid (University of Auckland)H-Index: 93
#2Anne Horne (University of Auckland)H-Index: 39
Last. Robert Scragg (University of Auckland)H-Index: 51
view all 11 authors...
Background Severe vitamin D deficiency causes osteomalacia, yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density (BMD) or fracture risk in adults. Objective To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels. Methods Two-year substudy of a trial in older community-resident adults. A total of 452 participants were randomized t...
37 CitationsSource
#1Anna FryH-Index: 1
Last. Naomi E. AllenH-Index: 87
view all 8 authors...
229 CitationsSource
#1Adrian Cortes (University of Oxford)H-Index: 20
#2Calliope A. Dendrou (University of Oxford)H-Index: 15
Last. Gilean McVean (University of Oxford)H-Index: 80
view all 10 authors...
Gil McVean and colleagues present a new Bayesian analysis framework that exploits the hierarchical structure of diagnosis classifications to analyze genetic variants against UK Biobank disease phenotypes derived from self-reporting and hospital episode statistics. Their method displays increased power to detect genetic effects over other approaches and identifies novel associations between classical HLA alleles and common immune-mediated diseases.
20 CitationsSource
#1Lauren E. MokryH-Index: 7
#2Stephanie RossH-Index: 16
Last. J. Brent RichardsH-Index: 45
view all 6 authors...
Objective: To test whether genetically decreased vitamin D levels are associated with Alzheimer disease (AD) using mendelian randomization (MR), a method that minimizes bias due to confounding or reverse causation. Methods: We selected single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels ( p −8 ) from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) Consortium (N = 33,996) to act as instrumental ...
39 CitationsSource
Cited By2
Newest
#2Angela BechtholdH-Index: 11
Last. Dorothee Volkert (FAU: University of Erlangen-Nuremberg)H-Index: 28
view all 14 authors...
Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevent...
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Abstract Vitamin D, used here to refer to both 25-hydroxyvitamin D, the main circulating form of the vitamin, and 1,25-hydroxyvitamin D, the biologically active form, has been shown to influence brain development and function. Consistent with these findings, low levels of vitamin D have been implicated in various mental disorders, including depression, schizophrenia, and autism. Recently, a shared variance across multiple categories of mental health disorders has been identified and shown to be ...
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We aimed to increase our understanding of the genetic determinants of vitamin D levels by undertaking a large-scale genome-wide association study (GWAS) of serum 25 hydroxyvitamin D (25OHD). To do so, we used imputed genotypes from 401,460 white British UK Biobank participants with available 25OHD levels, retaining single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) > 0.1% and imputation quality score > 0.3. We performed a linear mixed model GWAS on standardized log-transfor...
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