title: The genetics of common kidney disease: a pathway toward clinical relevance.
abstract: Genome-wide association studies (GWASs) have advanced our understanding of the genetic basis for common renal diseases, including chronic kidney disease (CKD) and related traits such as hypertension. The 'common variant, common disease' hypothesis-the theoretical basis for gene mapping by GWASs-has, however, underestimated the complexity of the genetic architecture underlying these diseases. The disease-specific variants identified by GWASs, despite being supported by statistically robust associations, often fail to illuminate the biology underlying the association and explain only a small portion of the estimated heritability of these diseases, even in aggregate. Although these variants have highlighted novel pathways that can be targeted therapeutically, their small effect sizes have minimal effects on diagnosis, prognosis, and management of individual patients. At present, therefore, the data do not support the routine use of genetic testing in the management of patients with CKD. Advances in technology, such as massively parallel gene sequencing, and characterization of alternative modes of inheritance should further elucidate the genetic architecture of CKD and provide tools to improve patient care.
authors.affiliation: Center for Study of Kidney Disease and Biology, 2500 MetroHealth Drive R415, Cleveland, OH 44109-1998, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Drawz
authors.forename: John R
authors.initials: JR
authors.lastname: Sedor
mesh_terms: D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007674:Kidney Diseases / Q000208:ethnology / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics; D008957:Models, Genetic; D020409:Molecular Motor Proteins / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D010597:Pharmacogenetics; D018570:Risk Assessment
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D005819:Genetic Markers; D008075:Lipoproteins, HDL; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains