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

AP Morris; TH Le; H Wu; A Akbarov; PJ van der Most; G Hemani; GD Smith; A Mahajan; KJ Gaulton; GN Nadkarni; A Valladares-Salgado; N Wacher-Rodarte; JC Mychaleckyj; ND Dueker; X Guo; Y Hai; J Haessler; Y Kamatani; AM Stilp; G Zhu; JP Cook; J Ärnlöv; SH Blanton; MH de Borst; EP Bottinger; TA Buchanan; S Cechova; FJ Charchar; PL Chu; J Damman; J Eales; AG Gharavi; V Giedraitis; AC Heath; E Ipp; K Kiryluk; HJ Kramer; M Kubo; A Larsson; CM Lindgren; Y Lu; PAF Madden; GW Montgomery; GJ Papanicolaou; LJ Raffel; RL Sacco; E Sanchez; H Stark; J Sundstrom; KD Taylor; AH Xiang; A Zivkovic; L Lind; E Ingelsson; NG Martin; JB Whitfield; J Cai; CC Laurie; Y Okada; K Matsuda; C Kooperberg; YDI Chen; T Rundek; SS Rich; RJF Loos; EJ Parra; M Cruz; JI Rotter; H Snieder; M Tomaszewski; BD Humphreys; N Franceschini

Journal article

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

AP Morris, TH Le, H Wu, A Akbarov, PJ van der Most, G Hemani, GD Smith, A Mahajan, KJ Gaulton, GN Nadkarni, A Valladares-Salgado, N Wacher-Rodarte, JC Mychaleckyj, ND Dueker, X Guo, Y Hai, J Haessler, Y Kamatani, AM Stilp, G Zhu Show all

Nature Communications | NATURE PORTFOLIO | Published : 2019

DOI: 10.1038/s41467-018-07867-7

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Abstract

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. Me..

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University of Melbourne Researchers

Mr Fadi Charchar Author

Grants

Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development

Funding Acknowledgements

T.H.L. is supported by the NIH (R01-DK-113632). G.H. is supported by the Wellcome Trust (208806/Z/17/Z). G.H. and G.D.S. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/1). C.M.L. is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds, the Oxford NIHR Biomedical Research Centre, Widenlife and the NIH (5P50-HD-028138-27). R.L.S. and T.R. are supported by the NIH (R37-NS-029993 and U54-TR-002736) and the Evelyn F McKnight Brain Institute. H.S. and A. Z. are supported by the DFG (INST 208/664-1). M.T. is supported the British Heart Foundation (PG/17/35/33001) and Kidney Research UK (RP_017_20180302). N.F. is supported by the NIH (R01-MD-012765, R56-DK-104806, and R01-DK-117445-01A1). Additional funding and acknowledgements can be found in Supplementary Note 1.