Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in…

• MG
  Massachusetts General Hospital
• GS
  Gilead Sciences
• CH
  Children's Hospital of Philadelphia

  Awards: P50DK114786, UL1TR001878, U01HG008680
• VU
  Vanderbilt University
• UO
  University of Pennsylvania

  Award: P30-DK19525
• NU
  Northwestern University

  Awards: U01HG008657, U01HG011167
• CC
  Cincinnati Children's Hospital Medical Center

  Award: U01HG011175
• UO
  University of Washington

  Awards: U01HG008680, U01HG006379, U01HG008685, U01HG008657, U01HG011181
• NT
  Norges Teknisk-Naturvitenskapelige Universitet
• RP
  Regeneron Pharmaceuticals
• VU
  Vanderbilt University Medical Center

  Award: U01HG011166
• GC
  Georgia Clinical and Translational Science Alliance
• UO
  University of Pennsylvania Health System
• NN
  National Natural Science Foundation of China
• NN
  Novo Nordisk
• HM
  Helse Midt-Norge
• NK
  Nemzeti Kutatási Fejlesztési és Innovációs Hivatal

  Award: K132695
• NI
  National Institutes of Health

  Awards: UL1TR001878, DK132630, DK126194, U01HG006379, P50DK114786, U01HG008680, U01HG008685, HD043483, DK105821, K12 HD043483, R01HG011345, U01HG011181, DK087635, DK19525, 813913, R01HL151152, P30-DK19525, DK050306, K24 HL157960, DK076077, P30-DK050306
• PS
  Perelman School of Medicine, University of Pennsylvania

  Awards: P30-DK050306, P30-DK19525, UL1TR001878
• MS
  Medical School, University of Michigan
• NI
  Norwegian Institute of Public Health
• NH
  National Human Genome Research Institute

  Awards: U01HG011175, U01HG008680, U01HG011176, U01HG008657, U01HG011167, U01HG011181, R01HG011345, U01HG008685, U01HG011166, U01HG011169, U01HG011172, U01HG006379
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: U01HG008680, UL1TR001878, DK105821, P30-DK19525, DK087635, DK076077, P50DK114786, DK126194, DK19525, DK050306, P30-DK050306
• NC
  National Center for Advancing Translational Sciences

  Awards: UL1TR001878, U01HG008680