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Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D: A large-scale Mendelian randomization study.
Medicine (Baltimore). 2020 Dec 18; 99(51):e23672.M

Abstract

ABSTRACT

Observational studies have reported that Vitamin D deficiency and the risk type 2 diabetes are associated, but the causation is unclear. Mendelian randomization (MR) involving genetic variants as instrument variables (IVs) overcomes the reverse-casualty and unmeasured confounding. However, with limited sample size and IVs, previous MR studies showed inconsistent results. Leveraging by a largely increased sample size for both stages, we aim to provide an updated and precise estimate for the causality between Vitamin D and type 2 diabetes.A 2-sample multi-IVs MR was performed. IVs for circulating 25-hydroxyvitamin D (25(OH)D) were obtained from a genome-wide association study from UK biobank involving 329,247 subjects of European ancestry. The causal effect of 25(OH)D and type 2 diabetes was estimated using traditional inverse variance weighting and MR pleiotropy residual sum and outlier (MR-PRESSO) framework which provides a robust estimate by systematically filtering out IVs identified with potential pleiotropy effects.A higher genetically instrumented 25(OH)D was causally linked to reduced risk of type 2 diabetes risk by MR-PRESSO [odds ratio (OR) per standard deviation (SD) = 0.950, 95% confidence interval (CI) = 0.913-0.988, P = .010] after removing 13 (13/193) invalid IVs. In addition, we confirmed the causal role Vitamin D using 2 synthesis-related single-nucleotide polymorphisms (SNPs) which are consistent with previous MR studies [OR per SD = 0.894, 95% CI = 0.816-0.979, P = .016].With a largely improved sample size, our results confirmed that genetically increased 25(OH)D concentration reduced the risk of type 2 diabetes and provided a more precise estimate for the effect size. The updated result empowers the role of Vitamin D and provides nontrivial evidence for interventional studies.

Authors+Show Affiliations

Department of Endocrine Rheumatism and nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University.Department of Pathology, Zhejiang University School of Medicine.Department of Endocrine Rheumatism and nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University.Department of Endocrine Rheumatism and nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University.Department of Endocrine Rheumatism and nephrology, The Third Affiliated Hospital of Zhejiang Chinese Medical University.Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

33371106

Citation

Xu, Yingying, et al. "Genetically Increased Circulating 25(OH)D Level Reduces the Risk of Type 2 Diabetes in Subjects With Deficiency of Vitamin D: a Large-scale Mendelian Randomization Study." Medicine, vol. 99, no. 51, 2020, pp. e23672.
Xu Y, Zhou Y, Liu J, et al. Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D: A large-scale Mendelian randomization study. Medicine (Baltimore). 2020;99(51):e23672.
Xu, Y., Zhou, Y., Liu, J., Wang, C., Qu, Z., Wei, Z., & Zhou, D. (2020). Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D: A large-scale Mendelian randomization study. Medicine, 99(51), e23672. https://doi.org/10.1097/MD.0000000000023672
Xu Y, et al. Genetically Increased Circulating 25(OH)D Level Reduces the Risk of Type 2 Diabetes in Subjects With Deficiency of Vitamin D: a Large-scale Mendelian Randomization Study. Medicine (Baltimore). 2020 Dec 18;99(51):e23672. PubMed PMID: 33371106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D: A large-scale Mendelian randomization study. AU - Xu,Yingying, AU - Zhou,Yuan, AU - Liu,Jingjing, AU - Wang,Chenfang, AU - Qu,Zhongjie, AU - Wei,Zhili, AU - Zhou,Dan, PY - 2020/02/13/received PY - 2020/11/10/accepted PY - 2020/12/29/entrez PY - 2020/12/30/pubmed PY - 2021/1/20/medline SP - e23672 EP - e23672 JF - Medicine JO - Medicine (Baltimore) VL - 99 IS - 51 N2 - ABSTRACT: Observational studies have reported that Vitamin D deficiency and the risk type 2 diabetes are associated, but the causation is unclear. Mendelian randomization (MR) involving genetic variants as instrument variables (IVs) overcomes the reverse-casualty and unmeasured confounding. However, with limited sample size and IVs, previous MR studies showed inconsistent results. Leveraging by a largely increased sample size for both stages, we aim to provide an updated and precise estimate for the causality between Vitamin D and type 2 diabetes.A 2-sample multi-IVs MR was performed. IVs for circulating 25-hydroxyvitamin D (25(OH)D) were obtained from a genome-wide association study from UK biobank involving 329,247 subjects of European ancestry. The causal effect of 25(OH)D and type 2 diabetes was estimated using traditional inverse variance weighting and MR pleiotropy residual sum and outlier (MR-PRESSO) framework which provides a robust estimate by systematically filtering out IVs identified with potential pleiotropy effects.A higher genetically instrumented 25(OH)D was causally linked to reduced risk of type 2 diabetes risk by MR-PRESSO [odds ratio (OR) per standard deviation (SD) = 0.950, 95% confidence interval (CI) = 0.913-0.988, P = .010] after removing 13 (13/193) invalid IVs. In addition, we confirmed the causal role Vitamin D using 2 synthesis-related single-nucleotide polymorphisms (SNPs) which are consistent with previous MR studies [OR per SD = 0.894, 95% CI = 0.816-0.979, P = .016].With a largely improved sample size, our results confirmed that genetically increased 25(OH)D concentration reduced the risk of type 2 diabetes and provided a more precise estimate for the effect size. The updated result empowers the role of Vitamin D and provides nontrivial evidence for interventional studies. SN - 1536-5964 UR - https://www.unboundmedicine.com/medline/citation/33371106/Genetically_increased_circulating_25_OH_D_level_reduces_the_risk_of_type_2_diabetes_in_subjects_with_deficiency_of_vitamin_D:_A_large_scale_Mendelian_randomization_study_ L2 - https://doi.org/10.1097/MD.0000000000023672 DB - PRIME DP - Unbound Medicine ER -