Neutralizing spurious associations

The finding is significant because such population structure can bias genome-wide association studies (GWASs) aimed at determining genetic links to disease, leading to spurious associations. On the basis of their work the researchers suggest ways of avoiding or correcting this bias.

GWASs are increasingly employed to reveal relationships between single nucleotide polymorphisms (SNPs) and particular disease conditions. The technique seeks out statistical differences among sets of polymorphic genetic markers between sufferers of a disease and a control group.

It has already supplied useful information about the genetic basis of asthma, cancer, diabetes, heart disease and mental illness. GWASs, however, assume that the two groups being compared are drawn from the same homogeneous population—that is, there is no underlying pattern of genetic difference between them other than susceptibility to the disease condition being tested.

Although the population as a whole does not show great genetic diversity, previous work by other researchers suggested that the Japanese fall into two genetic categories, perhaps reflecting two migration events. But these studies were of limited regions of the genome. So the RIKEN researchers embarked on a much broader investigation with greater relevance to GWASs. They published their results in a recent issue of The American Journal of Human Genetics (1).

Given the good quality of SNP data on the Japanese population, the researchers used statistical techniques mainly based on principal components analysis to check the homogeneity of genetic structure in a sample of 7,003 people drawn from all over Japan. They found strong evidence of the dual nature of the Japanese population. One genetic group, the Hondo cluster, includes most people from the main islands of Japan; the other, the much smaller Ryukyu cluster, includes most individuals from Okinawa and nearby islands.

The research also demonstrated how such population stratification could impact the results of GWASs using Japanese subjects. As a consequence, the researchers propose measures to avoid bias, such as excluding members from the Ryukyu cluster if they occur in small proportion, equalizing Ryukyu numbers in both disease and control groups, or using statistical techniques to compensate for any potential bias.

“The aim of our analysis is to improve methods for conducting GWASs,” says first author Yumi Yamaguchi-Kabata. “We now wish to broaden the work to encompass different local regions in Asia.”

Reference

1. Yamaguchi-Kabata, Y., Nakazono, K., Takahashi, A., Saito, S., Hosono, N., Kubo, M., Nakamura, Y. & Kamatani, N. Japanese population structure, based on SNP genotypes from 7003 individuals compared to other ethnic groups: Effects on population-based association studies. The American Journal of Human Genetics 83, 445–456 (2008).

The corresponding author for this highlight is based at the RIKEN Laboratory for Statistical Analysis

Media Contact

Saeko Okada ResearchSEA

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors