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However, the results of\nshort- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been\ninconsistent.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives and methods<\/jats:title>\n                <jats:p>To evaluate the causal role of reduced blood\n25(OH)D in T2D, here we have performed a bidirectional Mendelian randomization\nstudy using 59,890 individuals (5,862 T2D cases and 54,028 controls) from\nEuropean and Asian Indian ancestries. We used six known SNPs, including three\nT2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate\nthe causality and direction of the association between T2D and circulating\n25(OH)D concentration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Results of the combined meta-analysis of eight\nparticipating studies showed that a composite score of three T2D SNPs would\nsignificantly increase T2D risk by an odds ratio (OR) of 1.24, p\u2009=\u20091.82\u2009\u00d7\u200910<jats:sup>\u201332<\/jats:sup>; Z score 11.86, which, however, had\nno significant association with 25(OH)D status (Beta -0.02nmol\/L\u2009\u00b1\u2009SE\n0.01nmol\/L; p\u2009=\u20090.83; Z score -0.21). Likewise, the genetically\ninstrumented composite score of 25(OH)D lowering alleles significantly\ndecreased 25(OH)D concentrations (-2.1nmol\/L\u2009\u00b1\u2009SE 0.1nmol\/L,\np\u2009=\u20097.92\u2009\u00d7\u200910<jats:sup>\u201378<\/jats:sup>; Z score -18.68) but was not\nassociated with increased risk for T2D (OR 1.00, p\u2009=\u20090.12;\nZ score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an\nindividual genetic instrument, a per allele reduction of 25(OH)D concentration\n(-4.2nmol\/L\u2009\u00b1\u2009SE 0.3nmol\/L)\nwas predicted to increase T2D risk by 5%, p\u2009=\u20090.004;\nZ score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GC\nrs2282679, CYP2R1 rs12794714) when used as an individual instrument.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our new data on this bidirectional Mendelian\nrandomization study suggests that genetically instrumented T2D risk does not\ncause changes in 25(OH)D levels. However, genetically regulated 25(OH)D\ndeficiency due to vitamin D synthesis gene (DHCR7) may influence the risk of\nT2D.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12937-021-00725-1","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T08:02:57Z","timestamp":1627372977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["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"],"prefix":"10.1186","volume":"20","author":[{"given":"Cynthia A.","family":"Bejar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwali","family":"Goyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoaib","family":"Afzal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mangino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"van der Most","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipin","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa C.","family":"Smart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagandeep K.","family":"Walia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek","family":"Verweij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Power","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorairaj","family":"Prabhakaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai Rup","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narinder K.","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet S.","family":"Wander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarju","family":"Ralhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kinra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H.","family":"de Borst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Hypp\u00f6nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim D.","family":"Spector","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f8rge G.","family":"Nordestgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piers R.","family":"Blackett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharambir K.","family":"Sanghera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"issue":"2","key":"725_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.diabres.2013.11.002","volume":"103","author":"L Guariguata","year":"2014","unstructured":"Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. 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Photochem Photobiol Sci. 2017;16(3):362\u201373.","journal-title":"Photochem Photobiol Sci"}],"container-title":["Nutrition Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12937-021-00725-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12937-021-00725-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12937-021-00725-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T08:03:45Z","timestamp":1627373025000},"score":1,"resource":{"primary":{"URL":"https:\/\/nutritionj.biomedcentral.com\/articles\/10.1186\/s12937-021-00725-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,27]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["725"],"URL":"https:\/\/doi.org\/10.1186\/s12937-021-00725-1","relation":{},"ISSN":["1475-2891"],"issn-type":[{"value":"1475-2891","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,27]]},"assertion":[{"value":"4 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Asian Indian Diabetic Heart Study\/Sikh Diabetes Study (AIDHS\/SDS) was reviewed and approved by the University of Oklahoma Health Sciences Center Institutional Review Board (IRB#2911), as well as the Human Subject Protection Committee at the participating hospitals and institutes in India. IMS study was approved by ethics committee of the All India Institute of Medical Sciences, New Delhi, India (IRB# number A-60\/4\/8\/2004). Twins UK study obtained ethical approval from the Ethics Committee at Guy's and St Thomas Hospital Trust, London. Internal Ethical Committee reviewed the 1958 BC study. The Copenhagen City Heart Study (CCHS), the Copenhagen General Population Study (CGPS), and the Copenhagen Ischemic Heart Disease Study (CIHDS) studies were approved by the Danish Ethical Committees and Herlev Hospital, Copenhagen University Hospital. The UK Household Longitudinal Study (UKHLS) got ethical approval from the local ethics committee. The PREVEND study was approved by the local medical ethics committee and was conducted in accordance with the guidelines of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We declare that no conflict of interest could be perceived as prejudicing the impartiality of the research reported.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"71"}}