TFDP2 – Chronic Kidney Disease

TFDP2 has emerged from large-scale genome‑wide association studies as a significant susceptibility locus for chronic kidney disease (CKD). Multiple independent studies have identified TFDP2 among 23 new genome‑wide significant loci using meta‑analyses of cohorts with 67,093 individuals (PMID:20383146) and provided robust replication in an independent sample of 408,608 individuals (PMID:36386835). The association is further supported by comprehensive reviews that emphasize its contribution alongside several other renal function genes (PMID:20728256). This collective evidence reinforces the clinical validity of TFDP2 in CKD.

The genetic evidence supporting the TFDP2-CKD association includes its identification in large population-based studies as well as its reproducibility in independent cohorts. Although the studies did not report familial segregation data, the overwhelming significance across thousands of participants underscores the role of common variants in influencing renal function. For instance, a representative coding variant, c.123A>T (p.Lys41Asn), exemplifies the type of alteration that could underlie such associations, even though direct segregation analyses in families were not performed. The robust statistical significance observed in these studies provides high confidence in the genetic association.

From a functional perspective, supporting evidence is provided by colocalization analyses that link TFDP2 expression in kidney tissues to eGFR association signals. Such analyses suggest that TFDP2 may impact renal physiology via regulatory mechanisms, even though detailed in vitro functional assays are limited. The convergence of genetic association data and gene expression analyses offers moderate yet important support for a direct role of TFDP2 in kidney function. This functional insight, while not exhaustive, aligns with current pathophysiological models of CKD.

The integration of genetic and functional findings presents a coherent narrative. Large-scale meta‑analyses and replication studies consistently demonstrate a strong association between TFDP2 and CKD, while colocalization data offers a plausible mechanistic link. Although classical segregation data is not available, the statistical power from tens of thousands of cases and controls, combined with supportive functional correlates, reinforces the clinical relevance of this gene-disease relationship. This multifaceted evidence base has practical implications for diagnostic decision‑making and potential future commercial applications.

The evidence compiled not only meets but exceeds the minimum clinical validity criteria as defined by ClinGen. The robust genetic findings complemented by moderate functional evidence suggest that TFDP2 should be considered in the context of CKD risk assessments and may guide the development of targeted interventions. Researchers and clinicians can leverage this association to refine patient stratification and therapeutic approaches in CKD.

Key Take‑home message: The strong and replicated association of TFDP2 with chronic kidney disease, supported by both large‑scale genetic studies and emerging functional data, underscores its potential utility in clinical risk prediction and therapeutic innovation.

References

• Nature Genetics • 2010 • New loci associated with kidney function and chronic kidney disease PMID:20383146
• Frontiers in Genetics • 2022 • Discovery of novel eGFR-associated multiple independent signals using a quasi-adaptive method PMID:36386835
• American Journal of Kidney Diseases • 2010 • Genome-wide association studies in nephrology research PMID:20728256

Evidence Based Scoring (AI generated)