Tags

Type your tag names separated by a space and hit enter

Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults.
PLoS Med. 2018 05; 15(5):e1002566.PM

Abstract

BACKGROUND

Observational studies have reported that higher plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with lower risks of diabetes, but it is unclear if these associations are causal. The aim of this study was to test the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations.

METHODS AND FINDINGS

Data were available on four 25(OH)D single nucleotide polymorphisms (SNPs; n = 82,464), plasma 25(OH)D concentrations (n = 13,565), and cases with diabetes (n = 5,565) in the China Kadoorie Biobank (CKB). The effects on risk of diabetes were assessed by a genetic score using two 25(OH)D synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), with and without the addition of SNPs affecting the transport (GC/DBP-rs2282679) and catabolism (CYP24A1-rs6013897) of 25(OH)D. The CKB results were combined in a meta-analysis of 10 studies for the 2 synthesis SNPs (n = 58,312 cases) and 7 studies for all 4 SNPs (n = 32,796 cases). Mean (SD) 25(OH)D concentration was 62 (20) nmol/l in CKB, and the per allele effects of genetic scores on 25(OH)D were 2.87 (SE 0.39) for the synthesis SNPs and 3.54 (SE 0.32) for all SNPs. A 25-nmol/l higher biochemically measured 25(OH)D was associated with a 9% (95% CI: 0%-18%) lower risk of diabetes in CKB. In a meta-analysis of all studies, a 25-nmol/l higher genetically instrumented 25(OH)D concentration was associated with a 14% (95% CI: 3%-23%) lower risk of diabetes (p = 0.01) using the 2 synthesis SNPs. An equivalent difference in 25(OH)D using a genetic score with 4 SNPs was not significantly associated with diabetes (odds ratio 8%, 95% CI: -1% to 16%, lower risk, p = 0.07), but had some evidence of pleiotropy. A limitation of the meta-analysis was the access only to study level rather than individual level data.

CONCLUSIONS

The concordant risks of diabetes for biochemically measured and genetically instrumented differences in 25(OH)D using synthesis SNPs provide evidence for a causal effect of higher 25(OH)D for prevention of diabetes.

Authors+Show Affiliations

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, United Kingdom.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, United Kingdom.Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom. Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.Chinese Academy of Medical Sciences, Dong Cheng District, Beijing, China.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, United Kingdom.Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Chinese Academy of Medical Sciences, Dong Cheng District, Beijing, China.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.Chinese Academy of Medical Sciences, Dong Cheng District, Beijing, China. Department of Epidemiology and Biostatistics, Peking University Health Science Center, Peking University, Beijing, China.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29718904

Citation

Lu, Ling, et al. "Association of Vitamin D With Risk of Type 2 Diabetes: a Mendelian Randomisation Study in European and Chinese Adults." PLoS Medicine, vol. 15, no. 5, 2018, pp. e1002566.
Lu L, Bennett DA, Millwood IY, et al. Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults. PLoS Med. 2018;15(5):e1002566.
Lu, L., Bennett, D. A., Millwood, I. Y., Parish, S., McCarthy, M. I., Mahajan, A., Lin, X., Bragg, F., Guo, Y., Holmes, M. V., Afzal, S., Nordestgaard, B. G., Bian, Z., Hill, M., Walters, R. G., Li, L., Chen, Z., & Clarke, R. (2018). Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults. PLoS Medicine, 15(5), e1002566. https://doi.org/10.1371/journal.pmed.1002566
Lu L, et al. Association of Vitamin D With Risk of Type 2 Diabetes: a Mendelian Randomisation Study in European and Chinese Adults. PLoS Med. 2018;15(5):e1002566. PubMed PMID: 29718904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults. AU - Lu,Ling, AU - Bennett,Derrick A, AU - Millwood,Iona Y, AU - Parish,Sarah, AU - McCarthy,Mark I, AU - Mahajan,Anubha, AU - Lin,Xu, AU - Bragg,Fiona, AU - Guo,Yu, AU - Holmes,Michael V, AU - Afzal,Shoaib, AU - Nordestgaard,Børge G, AU - Bian,Zheng, AU - Hill,Michael, AU - Walters,Robin G, AU - Li,Liming, AU - Chen,Zhengming, AU - Clarke,Robert, Y1 - 2018/05/02/ PY - 2017/11/09/received PY - 2018/04/06/accepted PY - 2018/5/3/entrez PY - 2018/5/3/pubmed PY - 2019/2/12/medline SP - e1002566 EP - e1002566 JF - PLoS medicine JO - PLoS Med VL - 15 IS - 5 N2 - BACKGROUND: Observational studies have reported that higher plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with lower risks of diabetes, but it is unclear if these associations are causal. The aim of this study was to test the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations. METHODS AND FINDINGS: Data were available on four 25(OH)D single nucleotide polymorphisms (SNPs; n = 82,464), plasma 25(OH)D concentrations (n = 13,565), and cases with diabetes (n = 5,565) in the China Kadoorie Biobank (CKB). The effects on risk of diabetes were assessed by a genetic score using two 25(OH)D synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), with and without the addition of SNPs affecting the transport (GC/DBP-rs2282679) and catabolism (CYP24A1-rs6013897) of 25(OH)D. The CKB results were combined in a meta-analysis of 10 studies for the 2 synthesis SNPs (n = 58,312 cases) and 7 studies for all 4 SNPs (n = 32,796 cases). Mean (SD) 25(OH)D concentration was 62 (20) nmol/l in CKB, and the per allele effects of genetic scores on 25(OH)D were 2.87 (SE 0.39) for the synthesis SNPs and 3.54 (SE 0.32) for all SNPs. A 25-nmol/l higher biochemically measured 25(OH)D was associated with a 9% (95% CI: 0%-18%) lower risk of diabetes in CKB. In a meta-analysis of all studies, a 25-nmol/l higher genetically instrumented 25(OH)D concentration was associated with a 14% (95% CI: 3%-23%) lower risk of diabetes (p = 0.01) using the 2 synthesis SNPs. An equivalent difference in 25(OH)D using a genetic score with 4 SNPs was not significantly associated with diabetes (odds ratio 8%, 95% CI: -1% to 16%, lower risk, p = 0.07), but had some evidence of pleiotropy. A limitation of the meta-analysis was the access only to study level rather than individual level data. CONCLUSIONS: The concordant risks of diabetes for biochemically measured and genetically instrumented differences in 25(OH)D using synthesis SNPs provide evidence for a causal effect of higher 25(OH)D for prevention of diabetes. SN - 1549-1676 UR - https://www.unboundmedicine.com/medline/citation/29718904/Association_of_vitamin_D_with_risk_of_type_2_diabetes:_A_Mendelian_randomisation_study_in_European_and_Chinese_adults_ L2 - https://dx.plos.org/10.1371/journal.pmed.1002566 DB - PRIME DP - Unbound Medicine ER -