Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

Area of Science:

• Genetics
• Endocrinology
• Nephrology

Background:

• Fibroblast Growth Factor 23 (FGF23) is a hormone regulating phosphorus and vitamin D metabolism.
• FGF23 is implicated in chronic kidney disease (CKD)-mineral and bone disorders and cardiovascular risk.
• Understanding FGF23 regulation is crucial, with genetic variation potentially explaining individual differences.

Purpose of the Study:

• To identify genetic variants associated with circulating FGF23 concentrations.
• To investigate the relationship between genetic factors and FGF23 levels in a large cohort.

Main Methods:

• Meta-analysis of genome-wide association studies (GWAS) involving 16,624 participants of European ancestry.
• Focused on individuals with estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m².
• Evaluated single-nucleotide polymorphisms (SNPs) associated with FGF23 concentration, adjusting for covariates like age, sex, BMI, and eGFR.

Main Results:

• Identified 154 SNPs in five independent regions associated with FGF23 concentration.
• The strongest association was with rs17216707, located upstream of CYP24A1, an enzyme in vitamin D metabolism.
• Other significant loci included variants near RGS14 and SLC34A1 (renal phosphate transport gene).

Conclusions:

• Common genetic variants near genes involved in vitamin D metabolism and renal phosphate transport are linked to variations in FGF23 levels.
• These findings contribute to understanding the genetic underpinnings of FGF23 regulation.