Publication

Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies

COGENT Consortium, Morris, A. P., Le, T. H., Wu, H., Akbarov, A., van der Most, P. J., Hemani, G., Smith, G. D., Mahajan, A., Gaulton, K. J., Nadkarni, G. N., Valladares-Salgado, A., Wacher-Rodarte, N., Mychaleckyj, J. C., Dueker, N. D., Guo, X., Hai, Y., Haessler, J., Kamatani, Y., Stilp, A. M., Zhu, G., Cook, J. P., Arnlov, J., Blanton, S. H., de Borst, M. H., Bottinger, E. P., Buchanan, T. A., Cechova, S., Charchar, F. J., Chu, P-L., Damman, J., Eales, J., Gharavi, A. G., Giedraitis, V., Heath, A. C., Ipp, E., Kiryluk, K., Kramer, H. J., Kubo, M., Larsson, A., Lindgren, C. M., Lu, Y., Madden, P. A. F., Montgomery, G. W., Papanicolaou, G. J., Raffel, L. J., Sacco, R. L., Sanchez, E., Stark, H., Sundstrom, J. & Snieder, H., 3-Jan-2019, In : Nature Communications. 10, 1, 14 p., 29.

Research output: Contribution to journalArticleAcademicpeer-review

  • COGENT Consortium
  • Andrew P. Morris
  • Thu H. Le
  • Haojia Wu
  • Artur Akbarov
  • Peter J. van der Most
  • Gibran Hemani
  • George Davey Smith
  • Anubha Mahajan
  • Kyle J. Gaulton
  • Girish N. Nadkarni
  • Adan Valladares-Salgado
  • Niels Wacher-Rodarte
  • Josyf C. Mychaleckyj
  • Nicole D. Dueker
  • Xiuqing Guo
  • Yang Hai
  • Jeffrey Haessler
  • Yoichiro Kamatani
  • Adrienne M. Stilp
  • Gu Zhu
  • James P. Cook
  • Johan Arnlov
  • Susan H. Blanton
  • Martin H. de Borst
  • Erwin P. Bottinger
  • Thomas A. Buchanan
  • Sylvia Cechova
  • Fadi J. Charchar
  • Pei-Lun Chu
  • Jeffrey Damman
  • James Eales
  • Ali G. Gharavi
  • Vilmantas Giedraitis
  • Andrew C. Heath
  • Eli Ipp
  • Krzysztof Kiryluk
  • Holly J. Kramer
  • Michiaki Kubo
  • Anders Larsson
  • Cecilia M. Lindgren
  • Yingchang Lu
  • Pamela A. F. Madden
  • Grant W. Montgomery
  • George J. Papanicolaou
  • Leslie J. Raffel
  • Ralph L. Sacco
  • Elena Sanchez
  • Holger Stark
  • Johan Sundstrom
  • Harold Snieder

Chronic kidney disease (CKD) affects -10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

Original languageEnglish
Article number29
Number of pages14
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 3-Jan-2019

    Keywords

  • GENOME-WIDE ASSOCIATION, GLOMERULAR-FILTRATION-RATE, MENDELIAN RANDOMIZATION, GENOTYPE IMPUTATION, SERUM CREATININE, BLOOD-PRESSURE, CELL-TYPES, EXPRESSION, VARIANTS, LOCI

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