{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:51:24Z","timestamp":1780480284898,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019779","name":"Qatar National Library","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019779","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin D deficiency is highly prevalent in the Middle East despite abundant sunlight; however, most genetic studies have focused on common variants in Europeans only. We analyzed whole-genome sequences from 13,808 Qatar Biobank participants, evaluating rare variants (minor allele frequency 0.01\u20130.0001) for associations with serum 25-hydroxyvitamin D (25(OH)D) levels and deficiency risk (\u226420 ng\/mL) in independent discovery (n = 5885) and replication (n = 7767) cohorts, followed by meta-analyses. In quantitative analyses, the discovery cohort identified 41 genome-wide significant signals, including CD36 rs192198195 (p = 2.48 \u00d7 10\u22128), and replication found 46, including SLC16A7 rs889439631 (p = 2.19 \u00d7 10\u22128), implicating lipid metabolism pathways. In binary analyses, replication revealed POTEB3 rs2605913 (p = 2.8 \u00d7 10\u22128), while meta-analysis (n = 13,652) uncovered SLC25A37 rs952825245 (p = 5.15 \u00d7 10\u221212), a locus associated with cancer and vitamin D signaling. Rare-variant polygenic scores derived from discovery significantly predicted continuous (R2 = 0.146, p = 9.08 \u00d7 10\u221212) and binary traits (AUC = 0.548, OR = 0.99, p = 9.22 \u00d7 10\u22126) in replication. This first rare-variant GWAS of vitamin D in Middle Easterners identifies novel loci and pathways, underscores the contribution of ancestry-specific rare alleles, and supports integrating rare and common variants to guide precision management in high-burden populations.<\/jats:p>","DOI":"10.3390\/ijms26199481","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare-Variant Genome-Wide Association and Polygenic Score Assessment of Vitamin D Status in a Middle Eastern Population"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2737-0565","authenticated-orcid":false,"given":"Nagham Nafiz","family":"Hendi","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Applied Science University, Amman P.O. Box 11937, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umm-Kulthum","family":"Umlai","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-5983","authenticated-orcid":false,"given":"Omar","family":"Albagha","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-5279","authenticated-orcid":false,"given":"Georges","family":"Nemer","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut P.O. Box 110236, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hendi, N.N., and Nemer, G. (2025). SDR42E1 modulates vitamin D absorption and cancer pathogenesis: Insights from an in vitro model. Front. 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