Neural EGFL like 1 as a novel gene for Trabecular Bone Score in older adults: The Bushehr Elderly Health (BEH) program

Neural EGFL like 1 (NELL-1), is a secreted glycoprotein and stimulates osteogenic cell differentiation and bone mineralization. This study aimed to explore the relationship between NELL-1 and Trabecular Bone Score (TBS) as a novel tool for the evaluation of osteoporosis in an elderly population-based cohort study in Iran. A single-locus analysis was performed on TBS using data from 2,071 participants in the Bushehr Elderly Health (BEH) Program. The study investigated 376 independent single nucleotide polymorphisms (SNPs) within the NELL-1 on chromosome 11p15.1. The association between SNPs and the mean TBS L1 to L4 was analyzed through an additive model. Significant variants in the additive model (P-FDR<0.05) were further examined within dominant, recessive, over-dominant, and co-dominant models. Multiple linear regression was employed to assess the relationship between the genetic risk score (GRS) derived from significant SNPs and TBS. Three SNPs within the NELL-1 showed a statistically significant association with TBS after adjusting for age and sex. The associations for rs1901945 (beta = 0.013, P-FDR = 0.0007), rs1584851 (beta = -0.011, P-FDR = 0.0003), and rs58028601 (beta = 0.011, P-FDR = 0.0003) were significant in the additive model. Additionally, significant results were observed for rs1901945 and rs58028601 in the dominant model (P<0.05). The GRS showed a statistically significant relationship with TBS, considering adjustments for age, sex, Body Mass Index, type 2 diabetes, and smoking (beta = 0.077, P = 1.7x10(-5)). This study highlights the association of NELL-1 with TBS, underscoring its potential as a candidate for further research and personalized medicine concerning the impact of this gene on bone quality.