AUTHOR=Gou Zhaoyang , Li Fan , Qiao Fengzhen , Maimaititusvn Gulinuer , Liu Fang 

TITLE=Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study

JOURNAL=Frontiers in Nutrition

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1162442

DOI=10.3389/fnut.2023.1162442

ISSN=2296-861X

ABSTRACT=<sec><title>Background</title><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).</p></sec><sec><title>Methods</title><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.</p></sec><sec><title>Results</title><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 β:0.021, 95% CI: 0.005–0.036, <italic>p</italic> = 7.74 × 10<sup>–3</sup>; 25-OHD: IVW β: 0.041, 95% CI: 0.026–0.057, <italic>p</italic> = 2.50 × 10<sup>–7</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 β:0.182, 95% CI: 0.061–0.305, <italic>p</italic> = 3.25 × 10<sup>–3</sup>; 25-OHD: IVW β: 0.057, 95% CI = 0.017–0.096, <italic>p</italic> = 4.73 × 10<sup>–3</sup>). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept <italic>p</italic> = 5.1 × 10<sup>–5</sup>, 25-OHD intercept <italic>p</italic> = 6.4 × 10<sup>–4</sup> in forward analysis; Vit D intercept <italic>p</italic> = 6.6 × 10<sup>–4</sup>, 25-OHD intercept <italic>p</italic> = 1.9 × 10<sup>–3</sup> in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.</p></sec><sec><title>Conclusion</title><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.</p></sec>