Lessons from CKD-Related Genetic Association Studies-Moving Forward

Abstract

Over the past decade, genetic association studies have uncovered numerous determinants of kidney function in the general, diabetic, hypertensive, CKD, ESRD, and GN-based study populations (e.g., IgA nephropathy, membranous nephropathy, FSGS). These studies have led to numerous novel and unanticipated findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. In this review, we report on major discoveries and advances resulting from this rapidly progressing research domain. We also predict some of the next steps the nephrology community should embrace to accelerate the identification of genetic and molecular processes leading to kidney dysfunction, pathophysiologically based disease subgroups, and specific therapeutic targets, as we attempt to transition toward a more precision-based medicine approach.

Keywords: Genetic Association Studies; Hypertension, Renal; Hypertensive Nephropathy; Kidney Failure, Chronic; Renal Insufficiency, Chronic; chronic kidney disease; diabetes mellitus; genetic renal disease; genome wide association; glomerulonephritis; nephritis; nephrology; precision medicine; systems biology.

Figure 1.

Genome-wide association studies approach summary. K, thousand; M, million; MN, membranous nephropathy; SNP, single nucleotide polymorphism.

Figure 2.

Karyotype representing primary genome-wide significant associations (P<5×10⁻⁸) between single nucleotide polymorphisms and kidney-related phenotypes. The figure was generated using the PhenoGram tool (83). The ethnicity of the studied population is symbol-coded whereas the phenotype is color-coded. DKD, diabetic kidney disease; HIVAN, HIV-associated nephropathy; IgAN, IgA nephropathy; MN, membranous nephropathy.