- Design
- Genome-wide association study with polygenic scores and external validation
- Population
- About 470,000 UK Biobank participants; validation cohorts of 1,304 and 939
- Primary outcome
- Loci affecting filtration markers but not GFR; genetic bias in eGFR
- Effect
- 52 creatinine and 48 cystatin C loci; mean eGFR bias 3.8 (creatinine) vs 0.6 (cystatin C) mL/min/1.73 m²
A genome-wide study in about 470,000 UK Biobank participants identified 52 loci that affect serum creatinine and 48 that affect cystatin C without affecting true GFR. Creatinine loci clustered in muscle and energy metabolism; cystatin C loci in inflammation and immune pathways.
Polygenic scores estimated an average genetic bias of 3.8 mL/min/1.73 m² in creatinine-based eGFR (individual range −1.5 to 7.9) and 0.6 in cystatin C-based eGFR (range −3.5 to 4.7). Creatinine bias differed by self-reported race and tracked muscle mass. The findings were validated against measured GFR in two independent cohorts.
This helps explain why two patients with the same eGFR can have different measured GFR. It is research-stage and will not change eGFR reporting now, but it supports using combined creatinine–cystatin C equations or measured GFR when a decision depends on precision.
- Use combined creatinine–cystatin C eGFR when drug dosing or staging depends on precision
- Consider measured GFR at decision thresholds such as donor assessment
- Remember muscle mass alters creatinine-based eGFR
- Do not order genetic testing for eGFR interpretation
Why it matters
It shows part of eGFR error is inherited, not just muscle mass or diet.
Don't overread it
This is population genetics in mostly European-ancestry participants; it does not provide a clinical correction.
The statistics, in plain English
A polygenic score adds up many small genetic effects. A mean bias of 3.8 mL/min is small at normal kidney function but matters near thresholds, such as 30 or 60 mL/min. The narrower bias for cystatin C suggests it is less affected by these genetic factors than creatinine.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for nephrology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free