ArticlemedRxiv : the preprint server for health sciences2024
Multi-trait Analysis of GWAS for circulating FGF23 Identifies Novel Network Interactions Between HRG-HMGB1 and Cardiac Disease in CKD.
Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors at 4 institutions in 1 country.
Funding
Abstract
Background: Genome-wide association studies (GWAS) have identified numerous genetic loci associated with mineral metabolism (MM) markers but have exclusively focused on single-trait analysis. In this study, we performed a multi-trait analysis of GWAS (MTAG) of MM, exploring overlapping genetic architecture between traits, to identify novel genetic associations for fibroblast growth factor 23 (FGF23). Methods: We applied MTAG to genetic variants common to GWAS of 5 genetically correlated MM markers (calcium, phosphorus, FGF23, 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH)) in European-ancestry subjects. We integrated information from UKBioBank GWAS for blood levels for phosphate, 25(OH)D and calcium (n=366,484), and CHARGE GWAS for PTH (n=29,155) and FGF23 (n=16,624). We then used functional genomics to model interactive and dynamic networks to identify novel associations between genetic traits and circulating FGF23. Results: MTAG increased the effective sample size for all MM markers to n=50,325 for FGF23. After clumping, MTAG identified independent genome-wide significant SNPs for all traits, including 62 loci for FGF23. Many of these loci have not been previously reported in single-trait analyses. Through functional genomics we identified Histidine-rich glycoprotein ( Conclusion: Our findings highlight the importance of MTAG analysis of MM markers to boost the number of genome-wide significant loci for FGF23 to identify novel genetic traits. Functional genomics revealed novel networks that inform unique cellular functions and identified
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