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A Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans

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dc.contributor.authorBejar, C.A.
dc.contributor.authorGoyal, S.
dc.contributor.authorAfzal, S.
dc.contributor.authorMangino, M.
dc.contributor.authorZhou, A.
dc.contributor.authorHyppönen, E.
dc.contributor.authorSanghera, D.K.
dc.date.issued2021
dc.descriptionData source: Supplementary Information, https://nutritionj.biomedcentral.com/articles/10.1186/s12937-021-00725-1#Sec12
dc.description.abstractContext: Multiple observational studies have reported an inverse relationship between 25-hydroxy vitaminD concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent. Objectives and methods: To evaluate the causal role of reduced blood25(OH)D in T2D, here we have performeda bidirectional Mendelian randomization study using 59,890 individuals (5,862 T2D cases and 54,028 controls) from European and Asian Indian ancestries. We used six known SNPs, including three T2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate the causality and direction of the association between T2D and circulating 25(OH)D concentration. Results: Results of the combined meta-analysis of eight participating studies showed that a composite score of three T2D SNPs would signifcantly increase T2D risk by an odds ratio (OR) of 1.24, p=1.82× 10–32; Z score 11.86, which,however, had no signifcant association with 25(OH)D status (Beta -0.02nmol/L±SE0.01nmol/L; p=0.83; Z score-0.21). Likewise, the genetically instrumented composite score of 25(OH)D lowering alleles signifcantly decreased 25 (OH)D concentrations (-2.1nmol/L±SE 0.1nmol/L,p=7.92× 10–78; Z score -18.68) but was not associated with increased risk for T2D (OR 1.00, p=0.12;Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an individual genetic instrument, a per allele reduction of 25(OH)D concentration (-4.2nmol/L±SE 0.3nmol/L) was predicted to increase T2D risk by 5%, p=0.004;Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs(GCrs2282679, CYP2R1 rs12794714) when used as an individual instrument.
dc.identifier.citationNutrition Journal, 2021; 20(1):1-11
dc.identifier.doi10.1186/s12937-021-00725-1
dc.identifier.issn1475-2891
dc.identifier.issn1475-2891
dc.identifier.urihttps://hdl.handle.net/11541.2/148283
dc.language.isoen
dc.publisherBioMed Central
dc.relation.fundingNHMRC 11123603
dc.relation.fundingWellcome Trust and Medical Research Council
dc.relation.fundingNational Institute of Health
dc.relation.fundingMRC grant G0000934
dc.rightsCopyright 2021 The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License. (http://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.1186/s12937-021-00725-1
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectVitamin D Deficiency
dc.subjectVitamin D
dc.subjectPolymorphism, Single Nucleotide
dc.subjectMendelian Randomization Analysis
dc.subjectAsian People
dc.titleA Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12231120040001831 13231120030001831 s12937-021-00725-1.pdf
ror.mmsid9916553945201831

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