{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:10:56Z","timestamp":1778670656822,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":132,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Vitamin D is a pleiotropic regulator of immune, metabolic, and endocrine homeostasis and has been implicated in a broad spectrum of chronic diseases. Although genome\u2010wide association studies (GWAS) have identified numerous genetic variants associated with vitamin D\u2013related traits, most signals reside in noncoding regions, limiting biological interpretation and disease\u2010oriented translation. Here, we present an integrative analytical framework to interpret vitamin D\u2013associated genetic variation by linking variant\u2010level associations to cis\u2010regulatory architecture, gene\u2010level aggregation, and functional organization. Vitamin D\u2013related traits were curated from the GWAS Catalog using ontology\u2010guided criteria. Genome\u2010wide significant variants were functionally annotated and mapped to nearby genes using a standardized \u00b1\u200950\u2010kb cis\u2010regulatory window. Independent variants were aggregated at the gene level to prioritize robust candidate genes for downstream analysis. We found that vitamin D\u2013associated variants were widely distributed across the genome and were predominantly enriched in noncoding regulatory regions. Cis\u2010regulatory mapping revealed extensive SNP\u2013gene multiplicity, reflecting complex local regulatory architectures. Gene\u2010level aggregation identified a prioritized set of genes supported by multiple independent variants, which converged on pathways central to chronic disease biology, including immune regulation, metabolic processes, endocrine signaling, and intracellular signal transduction. Network\u2010based integration further revealed modular regulatory structures characterized by coordinated pathway convergence. Together, these results indicate that vitamin D\u2013associated genetic variation contributes to chronic disease susceptibility through coordinated cis\u2010regulatory and multigenic mechanisms rather than isolated gene effects.<\/jats:p>","DOI":"10.1155\/humu\/3304798","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T10:23:10Z","timestamp":1778667790000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Analysis of Vitamin D\u2013Associated Genetic Variants Reveals Cis\u2010Regulatory Architecture and Multigenic Mechanisms Underlying Chronic Disease\u2013Relevant 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