{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T23:41:21Z","timestamp":1778974881219,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Insulin-like growth factor 1 (IGF-1) plays a vital role in the attainment and maintenance of bone mass throughout life and is closely related to the stature of children. 25-Hydroxyvitamin D (25-OHD) is an intermediate of vitamin D (Vit D) metabolism and a key indicator of Vit D nutritional status. Multiple studies have revealed that IGF-1 levels undergo a non-significant increase after Vit D supplementation. Here, we analyzed the causal and reverse causal relationships between 25-OHD and IGF-1 levels using Mendelian randomization (MR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two-sample MR was used to estimate an unconfounded bidirectional causal relationship between the level of IGF-1 and those of Vit D and 25-OHD. Single nucleotide polymorphisms (SNPs) were filtered from genome-wide association studies (GWAS) after a comprehensive search of the Integrative Epidemiology Unit GWAS database. Several MR methods were employed, including inverse-variance weighted (IVW) method, and a sensitivity analysis was undertaken to detect whether pleiotropy or heterogeneity biased the MR results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically predicted IGF-1 was found to have a causal association with Vit D and serum 25-OHD levels, where Vit D and serum 25-OHD levels increased with increasing IGF-1 concentrations (Vit D: IVW \u03b2:0.021, 95% CI: 0.005\u20130.036, <jats:italic>p<\/jats:italic> = 7.74 \u00d7 10<jats:sup>\u20133<\/jats:sup>; 25-OHD: IVW \u03b2: 0.041, 95% CI: 0.026\u20130.057, <jats:italic>p<\/jats:italic> = 2.50 \u00d7 10<jats:sup>\u20137<\/jats:sup>). A reverse causal effect was also found, indicating Vit D and serum 25-OHD have a positive causal relationship with IGF-1 (Vit D: IVW \u03b2:0.182, 95% CI: 0.061\u20130.305, <jats:italic>p<\/jats:italic> = 3.25 \u00d7 10<jats:sup>\u20133<\/jats:sup>; 25-OHD: IVW \u03b2: 0.057, 95% CI = 0.017\u20130.096, <jats:italic>p<\/jats:italic> = 4.73 \u00d7 10<jats:sup>\u20133<\/jats:sup>). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept <jats:italic>p<\/jats:italic> = 5.1 \u00d7 10<jats:sup>\u20135<\/jats:sup>, 25-OHD intercept <jats:italic>p<\/jats:italic> = 6.4 \u00d7 10<jats:sup>\u20134<\/jats:sup> in forward analysis; Vit D intercept <jats:italic>p<\/jats:italic> = 6.6 \u00d7 10<jats:sup>\u20134<\/jats:sup>, 25-OHD intercept <jats:italic>p<\/jats:italic> = 1.9 \u00d7 10<jats:sup>\u20133<\/jats:sup> in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of the MR analysis provide evidence that IGF-1 has positive causal and reverse causal relationships with Vit D and serum 25-OHD, respectively, in European populations. Our findings also provide guidance for the prevention and treatment of short stature and other related diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2023.1162442","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T05:24:15Z","timestamp":1684301055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization 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