{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:26:35Z","timestamp":1783164395732,"version":"3.54.6"},"reference-count":55,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020771","name":"Young Scientists Fund of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204170"],"award-info":[{"award-number":["82204170"]}],"id":[{"id":"10.13039\/501100020771","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003999","name":"Science Fund for Creative Research Groups","doi-asserted-by":"publisher","award":["2024NSFTD0030"],"award-info":[{"award-number":["2024NSFTD0030"]}],"id":[{"id":"10.13039\/501100003999","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023780","name":"School of Public Health","doi-asserted-by":"publisher","award":["2023SY-03"],"award-info":[{"award-number":["2023SY-03"]}],"id":[{"id":"10.13039\/100023780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aimed to investigate the shared genetic architecture and causal relationship between serum 25OHD and BMD, providing insights into their underlying biological mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417 580) and estimated heel BMD (eBMD, N = 426 824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Despite a lack of global genetic correlation (rg=\u22120.001; P = .95), a statistically significant local signal was discovered at 5p11-5q11.9. Two-sample mendelian randomization (MR) indicated no causal association in the overall population (\u03b2=.003, 95% CI, \u22120.04 to 0.03; P = .93), while positive causal effects were observed in males (\u03b2=.005, 95% CI, 0.00 to 0.01; P = .03) and older individuals (\u03b2=.009, 95% CI, 0.00\u223c0.02; P = .01) according to one-sample MR. A total of 49 pleiotropic single-nucleotide variations (SNVs), with 4 novel SNVs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exocrine\/endocrine, and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among men and individuals older than 65 years. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae738","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T09:26:39Z","timestamp":1729502799000},"page":"1605-1616","source":"Crossref","is-referenced-by-count":4,"title":["Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7117-8804","authenticated-orcid":false,"given":"Linna","family":"Sha","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu 610041, Sichuan 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