Volume 90, Issue 4, Pages 764-773 (October 2016) Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function  Jiaojiao Jing, Cristian Pattaro, Anselm Hoppmann, Yukinori Okada, Caroline S. Fox, Anna Köttgen  Kidney International  Volume 90, Issue 4, Pages 764-773 (October 2016) DOI: 10.1016/j.kint.2016.04.004 Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 1 Four gene lists were identified by retrieval of abnormal kidney phenotypes on the Mouse Genome Informatics website. These lists were interrogated in the CKDGen dataset for single-nucleotide polymorphisms associated with eGFRcrea or UACR. The observed number of significant genes was compared with the number expected by chance. Significant enrichment (morphology/eGFR) is indicated using bold boxes. GFR, glomerular filtration rate; eGFRcrea, estimated glomerular filtration rate; KO, knockout; UACR, urinary albumin-to-creatinine ratio. Kidney International 2016 90, 764-773DOI: (10.1016/j.kint.2016.04.004) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 2 Venn diagram illustrating the number of genes in each investigated list and their overlap. Gene lists were derived from the Mouse Genome Informatics resource and contain human orthologs of genes that, when manipulated or mutated, give rise to the respective murine phenotypes: morphology (“abnormal kidney morphology”), urine protein (“abnormal urine protein level”), glomerular filtration rate (GFR) (“abnormal glomerular filtration rate”), and physiology (“abnormal kidney physiology”). Kidney International 2016 90, 764-773DOI: (10.1016/j.kint.2016.04.004) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 3 Number of observed genes containing associated single-nucleotide polymorphisms based on the investigated lists (dashed line) compared with the expected distribution based on 2000 lists generated at random (histogram). Significant enrichment was observed for the morphology list (a), but not for physiology (b) or GFR (c). The P values from permutation were < 5×10−4). Kidney International 2016 90, 764-773DOI: (10.1016/j.kint.2016.04.004) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 4 Regional association plots of novel estimated glomerular filtration–associated loci in the CKDGen Consortium: CYP26A1 (a), BMP4 (b), and LAMA5 (c). Between single-nucleotide polymorphisms (SNPs) linkage disequilibrium, expressed as the square of the correlation coefficient, is based on the 1000 Genomes EUR samples (phase 1, version 3). chr, chromosome. Kidney International 2016 90, 764-773DOI: (10.1016/j.kint.2016.04.004) Copyright © 2016 International Society of Nephrology Terms and Conditions

Figure 5 Regional association plots of the CYP24A1 locus before (a) and after conditioning on the nearby CKDGen association signal upstream of BCAS1 (b). After conditioning, single-nucleotide polymorphisms (SNPs) in CYP24A1 show genomewide significant associations with estimated glomerular filtration rate. Kidney International 2016 90, 764-773DOI: (10.1016/j.kint.2016.04.004) Copyright © 2016 International Society of Nephrology Terms and Conditions