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Polygenic risk scores for eGFR are associated with age at kidney failure
Kane E Collins1,2,3, Edmund Gilbert1,2, Vincent Mauduit4
1School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
Insights
Polygenic risk scores for decreased estimated glomerular filtration rate (eGFR) are linked to earlier kidney failure. Higher scores predict developing kidney failure approximately two years sooner, highlighting genetic influences on disease progression.
Area of Science:
- Nephrology
- Genetics
- Epidemiology
Background:
- Chronic kidney disease (CKD) has a complex genetic basis, involving both single-gene and multiple-gene factors.
- CKD progression is influenced by clinical factors like hypertension, diabetes, and proteinuria, all of which have genetic components quantifiable by polygenic risk scores.
Purpose of the Study:
- To investigate the association between polygenic risk scores for CKD-related traits and the age at which kidney failure develops.
- To determine if genetic predisposition influences the timing of kidney failure onset.
Main Methods:
- Utilized genome-wide genotype data from 10,586 kidney failure patients across 12 cohorts.
- Calculated polygenic risk scores for traits including hypertension, albuminuria, and decreased eGFR using established weights.
- Employed logistic regression to analyze the association between polygenic risk scores and age at kidney failure, stratified by primary kidney disease.
Main Results:
- Individuals with the highest polygenic risk scores for decreased eGFR experienced kidney failure approximately two years earlier than others (49.9 vs. 47.9 years).
- Each standard deviation increase in the decreased eGFR polygenic risk score correlated with higher odds of kidney failure before age 60 (OR=1.05).
- High decreased eGFR polygenic risk scores significantly increased the odds of early kidney failure (OR=1.26).
Conclusions:
- Decreased eGFR polygenic risk score is a significant factor contributing to the variability in the age of kidney failure development.
- Genetic predisposition, as measured by polygenic risk scores, plays a role in the timing of kidney failure onset.
Background:
The genetic architecture of chronic kidney disease (CKD) is complex, including monogenic and polygenic contributions. CKD progression to kidney failure is influenced by factors including male sex, baseline estimated glomerular filtration rate (eGFR), hypertension, diabetes, proteinuria, and the underlying kidney disease. These traits all have strong genetic components, which can be partially quantified using polygenic risk scores. This paper examines the association between polygenic risk scores for CKD-related traits and age at kidney failure development.
Methods:
Genome-wide genotype data from 10,586 patients with kidney failure were compiled from 12 cohorts. Polygenic risk scores for hypertension, albuminuria, rapid decline in eGFR, decreased total kidney volume, and decreased eGFR were calculated using weights from published independent population-scale genome-wide association studies. The association between each polygenic risk score and age at kidney failure was investigated using logistic regression models. The association between polygenic risk score and age at kidney failure was also investigated separately for each primary kidney disease.
Results:
Individuals in the highest 10% of polygenic risk score for decreased eGFR developed kidney failure 2 years earlier than those in the bottom 90% (49.9 years and 47.9 years, P = 5e-5). A standard deviation increase in decreased eGFR polygenic risk score was associated with increased odds of developing kidney failure before the age of 60 years (Odds ratio (OR) = 1.05; 95% CI 1.01-1.10; P = 0.01), as was high decreased eGFR polygenic risk score (OR = 1.26; 95% CI 1.08-1.46; P = 0.003).
Conclusions:
We conclude that decreased eGFR polygenic risk score explains a portion of the variation in age at development of kidney failure.
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