☆ 4.8 Article

Genome-wide polygenic score to predict chronic kidney disease across ancestries

NATURE MEDICINE (2022)

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Journal

NATURE MEDICINE
Volume 28, Issue 7, Pages 1412-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41591-022-01869-1

Keywords

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Categories

Biochemistry & Molecular Biology Cell Biology Medicine, Research & Experimental

Funding

  1. National Human Genome Research Institute eMERGE-IV [2U01HG008680-05, 1U01HG011167-01, 1U01HG011176-01]
  2. National Institute of Neurological Disorders and Stroke [U01NS041588]
  3. National Institute on Aging
  4. National Institutes of Health (NIH)
  5. Department of Health and Human Services
  6. NHLBI [R01HL055673, R01HL123782, R01HL092173, K24HL133373]
  7. UKBB [41849]
  8. [UG3DK114926]
  9. [RC2DK116690]
  10. [R01LM013061]
  11. [K25DK128563]
  12. [UL1TR001873]
  13. [R01HL151855]
  14. [UM1DK078616]

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A polygenic score for chronic kidney disease has been generated and optimized, showing reproducible performance across 15 cohorts of different ancestries. The study identified potentially clinically relevant thresholds and demonstrated the predictive effects of the score comparable to family history of the disease.
A new study generated and optimized a polygenic score for chronic kidney disease with reproducible performance across 15 cohorts of different ancestries, and identified potentially clinically relevant thresholds with predicted effects comparable to having a family history of the disease. 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.

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