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<p>Kidney disease disproportionately affects populations of African ancestry, yet most genetic studies have focused on Europeans. Here, we present a three-stage genome-wide association study meta-analysis of estimated glomerular filtration rate in ~26,000 individuals across Eastern, Western, and Southern Africa and ~81,000 African-ancestry individuals in the diaspora. Continental African meta-analysis identifies four independent genome-wide significant loci, including two previously unreported loci. Pan-African meta-analysis identifies 19 independent loci, including three previously unreported loci. Fine-mapping reveals four loci with high causality probability, and phenome-wide analyses demonstrate pleiotropic effects on cardiometabolic and immunological traits. Notably, <i>APOL1</i> high-risk variants strongly associated with kidney disease in African Americans show markedly lower frequency and attenuated effects in continental Africa, indicating potential distinct genetic architectures. Polygenic scores from genetically similar populations significantly outperformed those from distant cohorts. These findings demonstrate the necessity of conducting genomic research across diverse African populations to enable equitable health outcomes.</p>

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KidneyGenAfrica multi-cohort Genome-wide association study and polygenic prediction of kidney function in 110,000 Africans

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月10日

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  • Abram B. Kamiza,
  • Tinashe Chikowore,
  • Guanjie Chen,
  • Oyesola Ojewunmi,
  • Tafadzwa Machipisa,
  • Feng Zhou,
  • Richard Mayanja,
  • Sounkou Toure,
  • Opeyemi Soremekun,
  • Christopher Kintu,
  • Mariam Nakabuye,
  • Mine Koprulu,
  • Allan Kalungi,
  • Robert Kalyesubula,
  • Babatunde Salako,
  • Oyekanmi Nashiru,
  • Manuel Corpas,
  • Cassianne Robinson-Cohen,
  • Nora Franceschini,
  • Cristian Pattaro,
  • Anna Köttgen,
  • Dorothea Nitsch,
  • Claudia Langenberg,
  • Catherine Tcheandjieu,
  • Moffat Nyirenda,
  • Andrew P. Morris,
  • Jennifer Asimit,
  • Eleftheria Zeggini,
  • Charles Rotimi,
  • Michele Ramsay,
  • Adebowale Adeyemo,
  • June Fabian,
  • Amelia C. Crampin,
  • Jean-Tristan Brandenburg,
  • Segun Fatumo

摘要

Kidney disease disproportionately affects populations of African ancestry, yet most genetic studies have focused on Europeans. Here, we present a three-stage genome-wide association study meta-analysis of estimated glomerular filtration rate in ~26,000 individuals across Eastern, Western, and Southern Africa and ~81,000 African-ancestry individuals in the diaspora. Continental African meta-analysis identifies four independent genome-wide significant loci, including two previously unreported loci. Pan-African meta-analysis identifies 19 independent loci, including three previously unreported loci. Fine-mapping reveals four loci with high causality probability, and phenome-wide analyses demonstrate pleiotropic effects on cardiometabolic and immunological traits. Notably, APOL1 high-risk variants strongly associated with kidney disease in African Americans show markedly lower frequency and attenuated effects in continental Africa, indicating potential distinct genetic architectures. Polygenic scores from genetically similar populations significantly outperformed those from distant cohorts. These findings demonstrate the necessity of conducting genomic research across diverse African populations to enable equitable health outcomes.