Insulin-like Growth Factor 1 (IGF-1) is a critical peptide hormone that plays a pivotal role in growth, development, and cellular regulation. It is primarily synthesized in the liver under the stimulation of growth hormone (GH) and acts as a key mediator of GH's growth-promoting effects. IGF-1 plays a fundamental role in various physiological processes, including cellular proliferation, differentiation, and tissue growth. Its actions are particularly prominent during the pre-adolescent and adolescent stages, where it influences longitudinal bone growth and overall somatic development.
The role of IGF-1 in growth regulation has garnered significant attention in the field of developmental biology. Previous research has demonstrated a positive correlation between circulating IGF-1 levels and height in various populations. Higher levels of IGF-1 have been associated with increased linear growth during childhood and adolescence. Randomized controlled trials of GH treatment in individuals with idiopathic short stature (ISS) , aiming to increase IGF-1 levels and final adult height have yielded conflicting results. Consequently, understanding the causal relationship between IGF-1 levels and height SDS across different ages can provide valuable insights into the mechanisms underlying growth and height variation.
In recent years, genetic studies have made significant strides in elucidating the genetic basis of complex traits, including height. Polygenic Risk Scores (PRS) are genetic risk scores that capture the cumulative effect of multiple genetic variants associated with complex traits, such as IGF-1 levels. As such, these PRS provide a comprehensive assessment of an individual's genetic predisposition to higher or lower IGF-1 levels. Also, using genetic variants from large IGF-1 genome-wide association study (Sinnott Armstrong et al, 2021) as instruments for IGF-1, we have generated preliminary results using Mendelian randomization, showing strong evidence of a causal effect of IGF1 on height. We are seeking to replicate these results by undertaking a one-sample Mendelian randomization study in ALSPAC
Body composition has been shown to influence growth patterns and height disparities among populations. Body Mass Index (BMI) has been suggested as a potential confounding factor in the IGF-1-height relationship. Investigating the relationship between a PRS for IGF-1 and height can help us better understand the contribution of IGF-1 to height variation and may reveal mediating effects of weight and potential gene-environment interactions affecting growth patterns.
This study aims to contribute to the growing body of evidence on the associations between IGF-1 levels, IGF-1 PRS, and height SDS, in ALSPAC. Understanding the impact of IGF-1 and of its genetic predictor on height variation at different ages, while accounting for BMI can offer valuable insights into the pathophysiology of growth.