{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:39:30Z","timestamp":1792701570427,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet & Metabol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Vitamin D deficiency and Type 2 diabetes (T2D) are highly prevalent in South Asian populations. Observational studies report inverse associations between serum 25\u2010hydroxyvitamin D [25(OH)D] and T2D risk, but these findings may reflect confounding or reverse causation. We used Mendelian randomization (MR) to assess the association between genetically predicted 25(OH)D and T2D risk in South Asians.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a two\u2010sample MR analysis using publicly available OpenGWAS summary statistics. One variant (rs3755967) met the conventional genome\u2010wide significance threshold (\n p<\/jats:italic>\n \u2009<\u20095\u2009\u00d7\u200910\n \u22128<\/jats:sup>\n ), while two additional variants (rs2459139 and rs72744878) met an exploratory threshold (\n p<\/jats:italic>\n \u2009<\u20091\u2009\u00d7\u200910\n \u22126<\/jats:sup>\n ). The three variants served as instruments for serum 25(OH)D in a South Asian GWAS (ukb\u2010e\u201030890_CSA;\n n<\/jats:italic>\n \u2009=\u20097380; mean\n F<\/jats:italic>\n \u2010statistic\u2009=\u200929.6; total\n R<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20091.06%). The primary outcome was BMI\u2010unadjusted T2D (ebi\u2010a\u2010GCST90093109;\n n<\/jats:italic>\n \u2009=\u200950,533; 16,677 cases), with a BMI\u2010adjusted GWAS used for sensitivity analysis. The primary estimator was inverse\u2010variance weighted (IVW), supported by weighted\u2010median, MR\u2010Egger, simple\u2010mode, and weighted\u2010mode analyses. Heterogeneity and directional pleiotropy were assessed using Cochran's\n Q<\/jats:italic>\n and the MR\u2010Egger intercept, respectively. Partial participant overlap could not be excluded because UK Biobank contributed to both datasets.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The primary IVW analysis showed no statistically significant association between genetically predicted 25(OH)D and T2D risk (\n \u03b2<\/jats:italic>\n \u2009=\u20090.058, SE\u2009=\u20090.120,\n p<\/jats:italic>\n \u2009=\u20090.630; OR\u2009=\u20091.06, 95% CI: 0.83\u20131.36). Weighted\u2010median and mode\u2010based estimates were also non\u2010significant. The MR\u2010Egger estimate was highly imprecise (OR\u2009=\u200932.0, 95% CI: 0.11\u20139103) because only three instruments were available. No significant heterogeneity or directional pleiotropy was detected, although these tests had limited power. The BMI\u2010adjusted sensitivity analysis produced similar findings.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We found no statistically significant evidence of a linear association between genetically predicted serum 25(OH)D and T2D risk. However, the small exposure GWAS, limited instrument set, exploratory instrument threshold, and possible sample overlap mean that small\u2010to\u2010moderate causal effects cannot be excluded. Larger South Asian GWAS are needed for more definitive inference.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/edm2.70359","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:48:57Z","timestamp":1792698537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Genetically Predicted 25\u2010Hydroxyvitamin D and Type 2 Diabetes Risk in South Asians: An Exploratory Two\u2010Sample Mendelian Randomization Study"],"prefix":"10.1002","volume":"9","author":[{"given":"Adina","family":"Zaka","sequence":"first","affiliation":[{"name":"Rahbar Medical and Dental College Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6486-3093","authenticated-orcid":false,"given":"Suleman","family":"Khan","sequence":"additional","affiliation":[{"name":"Khyber Medical College Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9558-9338","authenticated-orcid":false,"given":"Asim","family":"Shah","sequence":"additional","affiliation":[{"name":"Khyber Medical College Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4937-5500","authenticated-orcid":false,"given":"Aizaz Anwar","family":"Khalid","sequence":"additional","affiliation":[{"name":"Peshawar Medical College Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8995-1058","authenticated-orcid":false,"given":"Ibrahim","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Dhaka Medical College and Hospital Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5681-6522","authenticated-orcid":false,"given":"A. B. M.","family":"Kamrul\u2010Hasan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Mymensingh Medical College Mymensingh Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/jod.jod_61_24"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889\u2010021\u201011888\u20101"},{"key":"e_1_2_12_4_1","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2025"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra070553"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2013.09.010"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.1201\/b18084","volume-title":"Mendelian Randomization: Methods for Using Genetic Variants in Causal Estimation","author":"Burgess S.","year":"2015"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(14)70184\u20106"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010022\u201003248\u20105"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010017\u20100255\u2010x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx102"},{"key":"e_1_2_12_16_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2023"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt179"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12937\u2010021\u201000725\u20101"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900906"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.7326\/M22\u20103018"},{"issue":"7","key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S2213-8587(21)00088-7","article-title":"Ethnicity\u2010Specific BMI Cutoffs for Obesity Based on Type 2 Diabetes Risk in England: A Population\u2010Based Cohort Study","volume":"9","author":"Caleyachetty R.","year":"2021","journal-title":"Lancet Diabetes and Endocrinology"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809944"}],"container-title":["Endocrinology, Diabetes & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70359","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/edm2.70359","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70359","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:49:02Z","timestamp":1792698542000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/edm2.70359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/edm2.70359"],"URL":"https:\/\/doi.org\/10.1002\/edm2.70359","archive":["Portico"],"relation":{},"ISSN":["2398-9238","2398-9238"],"issn-type":[{"value":"2398-9238","type":"print"},{"value":"2398-9238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"2026-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70359"}}