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bioRxiv · 10.1101/2020.09.04.283713

Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals

Stanzick, K.-J.·Li, Y.·Gorski, M.·Wuttke, M.·Pattaro, C.·Koettgen, A.·Stark, K. J.·Heid, I. M.·Winkler, T. W.
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Abstract

Chronic kidney disease (CKD) has a complex genetic underpinning. Genome-wide association studies (GWAS) of CKD-defining glomerular filtration rate (GFR) have identified hundreds of loci, but prioritization of variants and genes is challenging. To expand and refine GWAS discovery, we meta-analyzed GWAS data for creatinine-based estimated GFR (eGFRcrea) from the Chronic Kidney Disease Genetics Consortium (CKDGen, n=765,348, trans-ethnic) and UK Biobank (UKB, n=436,581, Europeans). The results (i) extend the number of eGFRcrea loci (424 loci; 201 novel; 8.9% eGFRcrea variance explained by 634 independent signals); (ii) improve fine-mapping resolution (138 99% credible sets with [≤]5 variants, 44 single-variant sets); (iii) ascertain likely kidney function relevance for 343 loci (consistent association with alternative biomarkers); and (iv) highlight 34 genes with strong evidence by a systematic Gene PrioritiSation (GPS). We provide a sortable, searchable and customizable GPS tool to navigate through the in silico functional evidence and select relevant targets for functional investigations.

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Stanzick, K.-J., Li, Y., Gorski, M., Wuttke, M., Pattaro, C., Koettgen, A., Stark, K. J., Heid, I. M., Winkler, T. W.. 2020-09-04. Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals. https://doi.org/10.1101/2020.09.04.283713

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