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Page 2 of 12 Cao et al. J Transl Genet Genom 2019;3:4. I https://doi.org/10.20517/jtgg.2018.16
[1]
disease (ESRD) . In 2015, 124,411 new patients were diagnosed with ESRD according to the United States
[2]
Renal Data System, reflecting the increasing burden of kidney failure . A possible explanation for increased
renal failure is that the symptoms of most patients are non-specific or even missing in early-stage CKDs
(stages 1 to 3). Therefore, timely diagnosis and treatment of patients at a high risk of progression in the early
stage is a major clinical concern.

A biomarker is a quantifiable and analyzable characteristic that serves as an indicator of disease status,
[3]
prognosis or response to therapeutic interventions . Proteinuria and kidney function parameters are reliable
and relatively non-invasive classical biomarkers; however, their sensitivity and specificity in detecting early
[4]
renal injury is not optimal . Moreover, they cannot provide pathological information at the molecular level.
Therefore, there is an urgent need to uncover novel biomarkers with high sensitivity and specificity.

Personalized medical approaches generally stratify patients based on their biological or genomic make-
up and thus optimize personalize management regimes. The genetic background has a strong influence
on a wide spectrum of CKDs. Therefore, genomic biomarkers are expected to provide additional
information regarding the etiology and mechanisms underlying CKD progression, as well as help identify
[5]
more homogeneous patient subgroups and increasingly targeted therapies . The use of new biomarkers
obtained via high-throughput technologies is expected in the future, together with vast improvements in
computational power applied to genomics, proteomics, and metabolomics studies using biological fluids and
[6]
renal biopsy tissue . So far, such studies have focused on optimzing development of new therapies, drug
[7]
selection and drug dosage .

The aim of personalized medicine is to enable clinicians to rapidly, efficiently and accurately determine
[8]
the most appropriate diagnosis and therapy for a patient . Genomic biomarkers may not only provide
information regarding the etiology and mechanisms underlying CKD progression but may also be used for
early diagnosis and for the selection of appropriate drugs, thereby personalizing therapy.

In this review, we first introduce commonly used genomic medicine methods. Then, we summarize
the potential genomic biomarker candidates of inherited and acquired CKD. Finally, we discuss the
opportunities and challenges offered by personalized genomic medicine.

OVERVIEW OF GENE VARIATIONS AND GENETIC TESTING
According to databases including Gencode, Ensembl and RefSeq, there are approximately 19,000 to 21,000
[9]
protein-coding genes in the human genome . Moreover, all humans share approximately 99.9% similarity in
[10]
their DNA .
Nucleotide-level variations occur frequently in the human genome, the most common being a single-nucleotide
polymorphism (SNP), which is a variation in a single nucleotide between genome sequences. Laboratories use
high-throughput whole genome sequencing for genotyping of all SNPs in an individual. SNPs are present at
[11]
> 1% within a given population and account for a majority of normal human genetic variations . Most SNPs
have no obvious phenotypic effects, although some can affect gene expression and susceptibility to certain
[12]
diseases . Earlier methods for genome screening for genetic etiologies of disease employed candidate gene
[13]
studies and linkage analysis. In 2005, the first genome-wide association study (GWAS) was performed . Since
then, GWASs have emerged as the most widely used tools to map risk-associated loci for complex pathologies
via analysis of the association between genome-wide markers and the disease.

Even though genetic predisposition of an individual is a critical factor in determining renal disease
manifestation, robust interactions between genetic predisposition and environmental factors strongly
influence the course of CKD. Only a few renal disorders, such as Alport syndrome (AS) and autosomal
dominant polycystic kidney disease (ADPKD), are caused by single-gene variations. Such disorders can