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Abstract: FR-PO298

Multi-Trait Analysis of Mineral Metabolism Markers Identifies Novel Genetic Associations for FGF23

Session Information

Category: Bone and Mineral Metabolism

  • 501 Bone and Mineral Metabolism: Basic

Authors

  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Vartanian, Nicholas, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Akwo, Elvis Abang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Perwad, Farzana, University of California San Francisco, San Francisco, California, United States
Background

Genome-wide association studies (GWAS) have identified numerous genetic loci associated with mineral metabolism markers but have exclusively focused on single-trait analysis. In this study, we performed a multi-trait analysis of GWAS data of mineral metabolism markers, exploring overlapping genetic architecture between the traits, to identify novel genetic associations for fibroblast growth factor 23.

Methods

We applied multi-trait analysis of GWAS (MTAG) to genetic variants common to GWAS of 5 genetically correlated mineral metabolism markers (phosphorus, FGF23, calcium and PTH) in European-ancestry subjects. We integrated information from the UKBioBank GWAS for phosphate and calcium (n=366,484), and two GWAS from the CHARGE consortium for PTH (n=29,155) and FGF23 (n=16,624).

Results

MTAG increased the effective sample size for all mineral metabolism markers, to n=50,325 for FGF23. After clumping, MTAG identified independent genome-wide significant SNPs for all traits, including 47 loci for FGF23. Many of these loci have not been previously reported in single-trait analyses, including loci involved in inflammation, lipid metabolism, glucose metabolism, and bone health.

Conclusion

MTAG boosted the number of genome-wide significant loci FGF23. Our findings highlight the importance of performing multi-trait analysis in GWAS studies of mineral metabolism markers to identify novel genetic associations. These genetic loci may provide insight into the biological mechanisms underlying mineral metabolism and may have implications for the development of therapies for mineral-related disorders.

Manhattan plot of the strength of association of genetic variants with circulating FGF23 after MTAG

Funding

  • NIDDK Support