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, Cynthia A.
dc.contributor.authorGoyal, Shiwali
dc.contributor.authorAfzal, Shoaib
dc.contributor.authorMangino, Massimo
dc.contributor.authorZhou, Ang
dc.contributor.authorvan der Most, Peter J.
dc.contributor.authorBao, Yanchun
dc.contributor.authorGupta, Vipin
dc.contributor.authorSmart, Melissa C.
dc.contributor.authorWalia, Gagandeep K.
dc.contributor.authorVerweij, Niek
dc.contributor.authorPower, Christine
dc.contributor.authorPrabhakaran, Dorairaj
dc.contributor.authorSingh, Jai Rup
dc.contributor.authorMehra, Narinder K.
dc.contributor.authorWander, Gurpreet S.
dc.contributor.authorRalhan, Sarju
dc.contributor.authorKinra, Sanjay
dc.contributor.authorKumari, Meena
dc.contributor.authorde Borst, Martin H.
dc.contributor.authorHypp�nen, Elina
dc.contributor.authorSpector, Tim D.
dc.contributor.authorNordestgaard, B�rge G.
dc.contributor.authorBlackett, Piers R.
dc.contributor.authorSanghera, Dharambir K.
dc.date.accessioned2024-01-21T10:54:02Z
dc.date.accessioned2024-08-14T07:40:48Z
dc.date.available2024-01-21T10:54:02Z
dc.date.available2024-08-14T07:40:48Z
dc.date.issued2021-07-27T00:00:00
dc.description.abstractContext: Multiple observational studies have reported aninverse relationship between 25-hydroxyvitaminD concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results ofshort- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have beeninconsistent. Objectives and methods: To evaluate the causal role of reduced blood25(OH)D in T2D, here we have performed a bidirectional Mendelian randomizationstudy using 59,890 individuals (5,862 T2D cases and 54,028 controls) fromEuropean and Asian Indian ancestries. We used six known SNPs, including threeT2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluatethe causality and direction of the association between T2D and circulating25(OH)D concentration. Results: Results of the combined meta-analysis of eightparticipating studies showed that a composite score of three T2D SNPs wouldsignificantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 � 10�32; Z score 11.86, which, however, hadno significant association with 25(OH)D status (Beta -0.02nmol/L � SE0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the geneticallyinstrumented composite score of 25(OH)D lowering alleles significantlydecreased 25(OH)D concentrations (-2.1nmol/L � SE 0.1nmol/L,p = 7.92 � 10�78; Z score -18.68) but was notassociated 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 anindividual 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. Conclusion: Our new data on this bidirectional Mendelianrandomization study suggests that genetically instrumented T2D risk does notcause changes in 25(OH)D levels. However, genetically regulated 25(OH)Ddeficiency due to vitamin D synthesis gene (DHCR7) may influence the risk ofT2D. � 2021, The Author(s).en_US
dc.identifier.doi10.1186/s12937-021-00725-1
dc.identifier.issn14752891
dc.identifier.urihttp://10.2.3.109/handle/32116/4191
dc.identifier.urlhttps://nutritionj.biomedcentral.com/articles/10.1186/s12937-021-00725-1
dc.language.isoen_USen_US
dc.publisherBioMed Central Ltden_US
dc.subjectAsian Continental Ancestry Groupen_US
dc.subjectDiabetes Mellitus, Type 2en_US
dc.subjectHumansen_US
dc.subjectMendelian Randomization Analysisen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectVitamin Den_US
dc.subjectVitamin D Deficiencyen_US
dc.subject25 hydroxyvitamin Den_US
dc.subjectvitamin Den_US
dc.subjectadulten_US
dc.subjectageden_US
dc.subjectalleleen_US
dc.subjectArticleen_US
dc.subjectcontrolled studyen_US
dc.subjectEuropeanen_US
dc.subjectfemaleen_US
dc.subjectgenetic associationen_US
dc.subjectgenotypeen_US
dc.subjecthumanen_US
dc.subjectmajor clinical studyen_US
dc.subjectmaleen_US
dc.subjectMendelian randomization analysisen_US
dc.subjectnon insulin dependent diabetes mellitusen_US
dc.subjectodds ratioen_US
dc.subjectphenotypeen_US
dc.subjectquality controlen_US
dc.subjectrisk assessmenten_US
dc.subjectsingle nucleotide polymorphismen_US
dc.subjectSouth Asianen_US
dc.subjectstatistical analysisen_US
dc.subjectvitamin blood levelen_US
dc.subjectAsian continental ancestry groupen_US
dc.subjectgeneticsen_US
dc.subjectmeta analysisen_US
dc.subjectvitamin D deficiencyen_US
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 Europeansen_US
dc.title.journalNutrition Journalen_US
dc.typeArticleen_US
dc.type.accesstypeOpen Accessen_US

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