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. 2021 Dec 10;118(15):3151–3161. doi: 10.1093/cvr/cvab357

Figure 1.

Figure 1

Overview of the strategy and the outputs of the study. (A) Conceptual overview of the study in four stages of MR studies. Stage 1—obesity traits and biochemical measures of kidney function, Stage 2—obesity traits and kidney health index, Stage 3—obesity traits and kidney disease, Stage 4—hypertension and diabetes as potential mediators of association between obesity traits and kidney health index. eGFRcrea, GFR estimated by creatinine; eGFRcys, GFR estimated by cystatin C; eGFRcreacys, GFR estimated by creatinine and cystatin C; BUN, blood urea nitrogen; SBP, systolic blood pressure; DBP, diastolic blood pressure; kidney health index, a composite renal phenotype integrating all available serum measures of kidney function (eGFRcrea, eGFRcys, eGFRcrea, and BUN), a uACR and the ICD-derived information on the history of kidney disease from hospital episode statistics. (B) Summary of the 50 most highly correlated phenotypes with kidney health index. Strength of statistical significance is shown by the size of the coloured circle, direction, and magnitude of association is shown by intensity of either blue (negative association) or red (positive association). All phenotypes are grouped and labelled by clinical category. (C) Summary of GSEA on canonical pathways for obesity traits alone and after adjustment for hypertension and diabetes. Strength of statistical significance is shown by the size of the coloured circle, direction, and magnitude of association is shown by intensity of either blue (negative association) or red (positive association), non-significant results after adjustment are coloured grey. All pathways are grouped and labelled by their biological theme. NFKB, ST Ga13 pathway; FCGR1, Reactome fcgamma receptor FCGR dependent phagocytosis; FCGR2, Reactome FCGR activation; FCGR3, Reactome FCGR3A-mediated IL10 synthesis; FCERI1, Reactome Fc epsilon receptor FCERI signalling; FCERI2, Reactome FCERI mediated Ca+2 mobilization; FCERI3, Reactome FCERI mediated MAPK activation; FCERI4, Reactome FCERI mediated NF-kB activation; Robos1, Reactome regulation of expression of SLITs and ROBOs; Robos2, Reactome signaling by ROBO receptors; RNA1, Reactome RRNA processing; RNA2, Reactome metabolism of RNA; RNA3, Reactome Nonsense-Mediated Decay; PIPS, Reactome synthesis of PIPS at the Golgi membrane; ENaC, Epithelial sodium channel; ECM1, Reactome MET activates PTK2 signaling; ECM2, Reactome MET promotes cell motility; ECM3, Reactome signaling by MET; PAKS, Reactome RHO GTPases activate PAKs.