| Title: | Genetic Variants, Serum 25-Hydroxyvitamin D Levels, and Sarcopenia |
| Journal: | JAMA Network Open |
| Published: | 1 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37647062/ |
| DOI: | https://doi.org/10.1001/jamanetworkopen.2023.31558 |
| URL: | https://escholarship.org/uc/item/99q849nt |
| Citations: | 6 (6 in last 2 years) as of 8 Aug 2024 |
Publication 10212
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Abstract
Importance: 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 >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's 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.</p>
Objective: To investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk.</p>
Design, Setting, and Participants: This genome-wide genetic association study was performed from August 2022 to February 2023 among the 295 489 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.</p>
Exposures: 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.</p>
Main Outcomes and Measures: The primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed.</p>
Results: The final genetic analyses included 295 489 participants (mean [SD] age, 56.3 [8.1] years; 139 216 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.</p>
Conclusions and Relevance: 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.</p>
9 Keywords
- Adult
- Calcifediol
- Female
- Humans
- Mendelian Randomization Analysis
- Middle Aged
- Sarcopenia
- Vitamin D
- Vitamins
8 Authors
- Tingting Sha
- Yilun Wang
- Yuqing Zhang
- Nancy E. Lane
- Changjun Li
- Jie Wei
- Chao Zeng
- Guanghua Lei
1 Application
| Application ID | Title |
|---|---|
| 77646 | Identification of genetic and environmental factors involved in the aetiology of rheumatic and musculoskeletal diseases |
Enabling scientific discoveries that improve human health