Disentangling the effects of body size and genetics on insulin-like growth factor-1 and its relationship to mortality

The number of Americans age 65 and older is expected to increase to over 98 million by 2060 and results in an increased demand for health services due to increased rates of aging-related diseases. Studies of traits that are associated with longevity, such as the insulin-like growth factor‑1 (IGF‑1) levels, may provide insights to mitigate effects of these diseases. The relationship between IGF‑1 and body mass index (BMI), another trait associated with morbidity and mortality, is unclear. Furthermore, only seven genetic loci are known to be associated with IGF‑1 levels. In this study, I analyzed data from the Long Life Family Study participants, a unique cohort of two-generation families. My analyses indicated that the relationship between IGF‑1 and BMI differs across age groups, and this pattern was also seen in non-Hispanic White, non-Hispanic Black, and Mexican American participants in the third National Health and Nutritional Examination Survey. Genetic analysis revealed a novel locus associated with IGF‑1 levels on chromosome 11 (LOD = 3.48) as well as a previously known region on chromosome 7p12.3 (p ≤ 0.00023), although the identity of the specific gene (or genes) involved is unclear. Greater serum IGF‑1 levels were associated with lower risk of mortality (HR = 0.61, 95% CI = 0.53–0.70, p = 1.4× 10−10), an association that was attenuated after adjusting for age; however, the genetic variants associated with IGF‑1 levels themselves were not associated with the risk of mortality. Additional genetic studies are required to elucidate the role that IGF‑1 plays in age-related morbidity and mortality. My study has contributed to our understanding of the interplay between genetic and environmental factors that influence IGF‑1 levels and this knowledge may enable the development of methods to mitigate the development of age-related diseases and improve public health