Geneticists uncover a trail of variants associated with kidney dysfunction, specifically among East Asian populations

Chronic kidney disease (CKD) can be associated with a wide range of symptoms and physiological abnormalities, with potentially severe consequences for patients. Credit: 2012 iStockphoto.com/IngramPublishing

The past decade has seen a steady torrent of data linking human genetic variants associated with disease risk, and yet many important gaps remain. For example, many of these studies have focused primarily on Caucasian populations in North America and Europe. The resulting data may be less relevant to other ethnic groups that may have accumulated distinct subsets of risk factors over the millennia since our ancestors first parted ways in Africa.

The Asian Genetic Epidemiology Network (AGEN) was formed to address this issue by identifying disease risk loci specific to . A new study from AGEN-affiliated scientists has now identified 17 genomic sites that potentially predispose East Asian individuals to (CKD). CKD, which puts patients at risk of and cardiovascular disease, encompasses a host of potential metabolic symptoms. Accordingly, project leaders Yukinori Okada and Toshihiro Tanaka of the RIKEN Center for Genomic Medicine designed their study to identify potential genetic variants linked with four different physiological manifestations of CKD.

The AGEN Consortium is attempting to identify genetic markers and variants that might flag elements of disease risk specifically prevalent in the genomes of Asian individuals. Credit: 2012 iStockphoto.com/francisblack

They performed what is known as a meta-analysis, conducting a broad examination of obtained from 11 previously-studied cohorts comprising over 70,000 East Asian individuals. In particular, they were interested in identifying tiny variations known as single- (SNPs) that appear to be associated with CKD symptoms. This yielded 25 candidate loci, which the AGEN team then double-checked against another dataset obtained from nearly 20,000 more East Asian subjects.

Alongside several previously-identified potential risk factors, their analysis uncovered 17 loci that appear to be meaningfully linked with CKD. Importantly, only a subset of these showed equally strong association with CKD symptoms in datasets obtained from large numbers of Caucasians. They were also able to identify individual variants linked to multiple CKD manifestations, including SNPs within three genes that were significantly associated with all four symptoms selected for this study.

Several of the SNPs identified here were linked to genes involved in immunity and embryonic development, including one gene with an established role in the formation of the kidney. At least three others have been tied to kidney function in previous studies. For many of the other genes identified, however, the connection to kidney or metabolic disease remains unclear, and further study will be required to assemble these diverse data into a coherent map of CKD etiology and to understand which factors are particularly important 'red flags' for health risk in East Asian patients.

More information: Okada, Y., Sim, X., Go, M.J., Wu, J.-Y., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P. et al. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nature Genetics 44, 904–909 (2012).

add to favorites email to friend print save as pdf

Related Stories

Finding genes that expand waistlines

Jul 20, 2012

Some common genetic variants associated with obesity in east Asians have been identified by two international research teams involving RIKEN researchers. Yukinori Okada and Toshihiro Tanaka at the RIKEN Center ...

Recommended for you

A nucleotide change could initiate fragile X syndrome

9 hours ago

Researchers reveal how the alteration of a single nucleotide—the basic building block of DNA—could initiate fragile X syndrome, the most common inherited form of intellectual disability. The study appears ...

Gene clues to glaucoma risk

Aug 31, 2014

Scientists on Sunday said they had identified six genetic variants linked to glaucoma, a discovery that should help earlier diagnosis and better treatment for this often-debilitating eye disease.

Mutation disables innate immune system

Aug 29, 2014

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

User comments