Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 publication

DOI

10.1038/s41467-018-07867-7

Type

Journal article

Journal

Nature communications

Publication Date

03/01/2019

Volume

10

Addresses

Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK. apmorris@liverpool.ac.uk.

Keywords

Kidney, Humans, Kidney Calculi, Hypertension, Histones, Glomerular Filtration Rate, Histone Code, Blood Pressure, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Ethnic Groups, Female, Male, Renal Insufficiency, Chronic, Genome-Wide Association Study, Genetic Loci