rs115403343 (CFAP53P1/INTS6P1): Kidney Function

Key takeaways

• rs115403343 was identified in a trans-ancestry genetic study of over one million individuals as linked to kidney filtration rate.
• The variant is located near CFAP53P1 and INTS6P1, which are pseudogenes - DNA sequences that resemble genes but do not produce functional proteins.
• Together, all eGFR-linked variants found in this study explain about 7% of the variation in kidney filtration rate across the study population.
• A genetic risk score built from eGFR-lowering variants was associated with diagnosed chronic kidney disease in over 450,000 additional people.
• No specific effect size for rs115403343 alone is reported in the available source material; the evidence described here reflects the broader study context.

What the research says rs115403343, near the CFAP53P1 - INTS6P1 pseudogene locus, was among 308 loci reaching genome-wide significance for estimated glomerular filtration rate (eGFR - a blood test-derived estimate of how much blood the kidneys filter per minute) in a trans-ancestry discovery meta-analysis of 765,348 individuals, with independent replication in 280,722 participants from the Million Veteran Program (combined n > 1,046,070). After replication, 264 loci were confirmed - 166 of them newly identified - and 147 of those 264 also showed corroborating associations with blood urea nitrogen (BUN; n = 416,178), a separate kidney function marker. A genetic risk score built from eGFR-associated variants was additionally associated with clinically diagnosed chronic kidney disease (CKD) in 452,264 separate individuals.

Reported associations

• Estimated glomerular filtration rate (eGFR): rs115403343 is among the eGFR-associated variants identified at genome-wide significance in a trans-ancestry GWAS meta-analysis (combined n > 1,046,070). The full set of 308 discovery index SNPs explained 7.1% of eGFR variance and approximately 19.6% of eGFR genetic heritability (estimated heritability h = 39%, 95% credible interval 32% to 47%).
• Chronic kidney disease (CKD): A genetic risk score incorporating eGFR-lowering variants showed association with clinically diagnosed CKD in 452,264 independent individuals, supporting the relevance of this class of loci to CKD as a disease endpoint.

Evidence quality This locus was identified in one of the largest kidney function GWAS conducted to date, with discovery in 765,348 individuals spanning European, East Asian, African-American, South Asian, and Hispanic ancestry groups, and independent replication in 280,722 participants (combined n > 1,046,070). Of 308 discovery loci, 264 survived independent replication. Pathway analyses and enrichment in mouse models with renal phenotypes support the kidney as the primary target organ for eGFR-associated loci as a group. Colocalization analyses across 46 human tissues identified 17 genes differentially expressed in kidney among the broader set of loci, and fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. However, the source material does not report a variant-specific effect size, p-value, or tissue expression result for rs115403343 individually, and no independent studies specific to this variant are available here. Evidence strength for this particular locus, as distinguished from the broader set of 264 replicated eGFR loci, cannot be assessed from the materials provided.

Lifestyle considerations No lifestyle considerations on file for this variant.