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Genome-wide polygenic score to predict chronic kidney disease across ancestries
- Source :
- Nat Med
- Publication Year :
- 2021
-
Abstract
- Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD. The new GPS was tested in 15 independent cohorts, including 3 cohorts of European ancestry (n = 97,050), 6 cohorts of African ancestry (n = 14,544), 4 cohorts of Asian ancestry (n = 8,625) and 2 admixed Latinx cohorts (n = 3,625). We demonstrated score transferability with reproducible performance across all tested cohorts. The top 2% of the GPS was associated with nearly threefold increased risk of CKD across ancestries. In African ancestry cohorts, the APOL1 risk genotype and polygenic component of the GPS had additive effects on the risk of CKD.
- Subjects :
- Multifactorial Inheritance
Genotype
General Medicine
Apolipoprotein L1
Polymorphism, Single Nucleotide
Article
General Biochemistry, Genetics and Molecular Biology
Gene Frequency
Risk Factors
Humans
Genetic Predisposition to Disease
Renal Insufficiency, Chronic
Alleles
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 1546170X
- Volume :
- 28
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....7c5cba6417300ff2da91b4f3bf828920