Abstract: FR-PO1022
Mendelian Randomization of Hypothyroidism and Kidney Function in Veterans
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Hinojosa, Sebastian, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Triozzi, Jefferson Lorenzo, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Wang, Guanchao, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Hung, Adriana, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Group or Team Name
- Million Veteran Program.
Background
Hypothyroidism and chronic kidney disease (CKD) are highly prevalent conditions with a potential mechanistic link. A previous study in women from the WGHS (N 3336) demonstrated an association of hypothyroidism and CKD.
We studied the association of genetically predicted hypothyroidism in MVP, a large cohort composed of 93% men (exposure), and kidney function (outcome). The outcomes were creatinine-based GFR and cystatin-based GFR (both log-transformed) from CKDGen. We replicated our findings using two additional genetic datasets for the exposure.
Methods
Two-sample MR was conducted to study the associations between hypothyroidism and kidney function. The primary genetic instrument of the exposure for MR was derived from GWAS of hypothyroidism using data from MVP in 289,307 European American individuals (18,740 cases, 270,567 controls). We repeated the analysis in the FinnGen study (26,064 cases, 59,912 controls) and in UKBB (16,376 cases, 320,783 controls). In MVP and UKBB, the definition of hypothyroidism was based on diagnosis codes, and in FinnGen, on levothyroxine prescription purchases. The outcome was evaluated using summary statistics from GWAS for eGFR from CKDGen for eGFR creatinine (N 133,413) and eGFR-cystatin (N 32,834).
Results
Genetically predicted hypothyroidism demonstrated a causal relation with the risk of lower kidney function. In our primary analysis Cohorts: MVP/CKDGen (beta (SE): -0.009 (0.002), p 0.001). Results were consistent in sensitivity and replication analyses, as shown in Table 1. There was no evidence of horizontal pleiotropy.
Conclusion
Our study findings support that hypothyroidism is causally associated with lower kidney function. The mendelian randomization methodology supports a causal relationship and is less susceptible to confounding and reverse causation biases.
Exposure hypothyroidism; Outcome GFR
| MVP | UKBB | Finn | MVP | UKBB | Finn | |
| Hypothyroidism #Cases/Control | 63629/384460 | 16376/320783 | 26064/59912 | 63629/384460 | 16376/320783 | 26064/59912 |
| GFR-creatinine | GFR-cystatin C | |||||
| Sample Size | 133413 | 133413 | 133413 | 32834 | 32834 | 32834 |
| n_SNP | 68 | 59 | 20 | 156 | 58 | 20 |
| IVW (beta) | -0.0092 | -0.1191 | -0.009 | -0.0053 | -0.1983 | -0.0133 |
| p-value | 0.0012 | 0.0004 | 0.0062 | 0.0073 | 0.0072 | 0.0544 |
| W_Median (beta) | -0.0089 | -0.1242 | -0.009 | 0.002 | -0.2087 | -0.0004 |
| p-value | 0.0007 | 0.003 | 0.0002 | 0.1572 | 0.0204 | 0.9352 |
| MR_Egger (beta) | -0.0126 | -0.1818 | -0.014 | -0.0019 | -0.3552 | -0.018 |
| p-value | 0.0226 | 0.02 | 0.1596 | 0.653 | 0.0431 | 0.3653 |
Funding
- Veterans Affairs Support