{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:25:58Z","timestamp":1792081558439,"version":"4.4.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Vitamin D deficiency is commonly associated with sarcopenia; however, the latest International Clinical Practice Guidelines for Sarcopenia do not recommend vitamin D supplementation for sarcopenia owing to a lack of an apparent therapeutic effect on the indices of sarcopenia among participants with replete vitamin D concentration (ie, 25-hydroxyvitamin D [25(OH)D] level &amp;gt;20 ng\/mL) from randomized clinical trials. While there is consensus in all vitamin D guidelines that serum levels of 25(OH)D less than 10 ng\/mL should be corrected, approximately 30% of the world population\u2019s 25(OH)D levels range from 10 to 20 ng\/mL, and it remains unclear whether such suboptimal levels can maintain optimal health, including sarcopenia risk.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This genome-wide genetic association study was performed from August 2022 to February 2023 among the 295\u202f489 unrelated European participants from the UK Biobank (2006-2010). Nonlinear and standard mendelian randomization analyses were used to examine the association of serum 25(OH)D concentration with sarcopenia risk.<\/jats:p><\/jats:sec>Exposures<\/jats:title>A weighted genetic risk score using 35 unrelated single-nucleotide variants from the UK Biobank and weights from the SUNLIGHT Consortium was selected as an instrumental variable for serum 25(OH)D concentration.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed.<\/jats:p><\/jats:sec>Results<\/jats:title>The final genetic analyses included 295\u202f489 participants (mean [SD] age, 56.3 [8.1] years; 139\u202f216 female [52.9%]). There was an L-shaped association between genetically predicted serum 25(OH)D concentration and sarcopenia risk. The risk of sarcopenia decreased rapidly as 25(OH)D concentration increased until 20 ng\/mL and then leveled off. The odds ratio of sarcopenia for serum 25(OH)D level of 10 vs 20 ng\/mL was 1.74 (95% CI, 1.17-2.59). Similar patterns were also observed when the association between serum 25(OH)D concentration and risks of each of the sarcopenia indices were evaluated.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this mendelian randomization genetic association study of adults in the UK Biobank, the findings supported a nonlinear association between suboptimal 25(OH)D levels and sarcopenia risk. Randomized clinical trials among participants with suboptimal 25(OH)D levels are required to verify the potential causality.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.31558","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T15:36:00Z","timestamp":1693409760000},"page":"e2331558","source":"Crossref","is-referenced-by-count":46,"title":["Genetic Variants, Serum 25-Hydroxyvitamin D Levels, and Sarcopenia"],"prefix":"10.1001","volume":"6","author":[{"given":"Tingting","family":"Sha","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China"},{"name":"Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Changsha, 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Department of Medicine, University of California School of Medicine, Sacramento"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjun","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wei","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China"},{"name":"Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Changsha, China"},{"name":"Health Management Center, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, 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