Table 1.
Methods and summary estimates from mendelian randomization studies of FGF23 and heart failure phenotypes
| Study (First Author, Journal, Publication date) | FGF23 GWAS | FGF23 Instruments | Source of Outcome data (n = number of HF cases) | MR IVW OR (95%CI) |
|---|---|---|---|---|
|
| ||||
| Liang Y et al. Frontiers in Genetics 07/23/2021 | CHARGE Consortium, FGF23 GWAS meta-analysis, n =16,624 | 4 SNPs with p<5×10−8 (rs17216707 near CYP24A1, rs11741640 near RGS14, rs17479566 near LINC01229, rs9925837 near LINC01506) | HERMES (n = 47,309) | 0.99 (0.75, 1.31) |
|
| ||||
| Akwo E et al CJASN 08/01/2022 | CHARGE Consortium, FGF23 GWAS meta-analysis, n=16,624 | 4 SNPs with p<5×10−8 (rs17216707 near CYP24A1, rs11741640 near RGS14, rs17479566 near LINC01229, rs9925837 near LINC01506) | Overall HF | |
| HERMES (n = 47,309) | 1.13 (0.89, 1.42) | |||
| BioVU, Overall (n = 18,415) | 1.32 (0.95, 1.84) | |||
| BioVU, low eGFR PRSa (n=3086) | 3.09 (1.38, 6.91) | |||
| BioVU, low eGFR PRSa (n=15,329) | 1.11 (0.77, 1.54) | |||
| HFpEF | ||||
| BioVU, Overall (n = 13,141) | 1.47 (1.01, 2.14) | |||
| BioVU, low eGFR PRSa (n=2223) | 7.20 (2.80, 18.5) | |||
| BioVU, low eGFR PRSa (n=10,918) | 1.03 (0.67, 1.57) | |||
| HFrEF | ||||
| BioVU, Overall (n = 3394) | 0.86 (0.38, 1.96) | |||
| BioVU, low eGFR PRSa (n=554) | 0.24 (0.03, 1.72) | |||
| BioVU, low eGFR PRSa (n=2840) | 1.12 (0.45, 2.77) | |||
|
| ||||
| Donovan et al CJASN 01/01/2023 | SCALLOP Consortium, FGF23 GWAS meta-analysis, n = 19,195 | Genetic score of 34 SNPs with p<5×10−6 | HERMES (n = 47,309) | 1.00 (0.94, 1.05) |
|
| ||||
| UK Biobank (n=10,177) | 1.01 (0.94, 1.10) | |||
|
| ||||
| Henry et al Circulation 04/19/2022 | SCALLOP Consortium, FGF23 GWAS meta-analysis, n = 19,195 | 1 Cis-variant (rs6489536) near the FGF23 gene with p < 5×10−8 | HERMES (n = 47,309) | 0.79 (0.62, 1.02) |
|
| ||||
| 2 Cis-variants (rs6489536 and rs7955866) near the FGF23 gene with p < 1×10−6 | HERMES (n = 47,309) | 0.80 (0.71–0.89) | ||
BioVU, Vanderbilt University Medical Center DNA Biobank; CHARGE, Cohorts for Heart and Aging Research in Genetic Epidemiology; eGFR, estimated Glomerular Filtration Rate; FGF23, Fibroblast Growth Factor-23; GWAS, Genome-Wide Association Study; HERMES, Heart Failure Molecular Epidemiology Therapeutic Targets; HF, heart failure; HFpEF heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IVW, Inverse Variance Weighted; MR, mendelian randomization; OR, Odds Ratio; PRS, Polygenic Risk Score; SNP, single nucleotide polymorphism