January 11, 2008

Genes, disease and ethnicity

Statistical analyses demonstrate variability in association between genes and osteoarthritis links to ethnicity

x-ray image of hip joint

Figure 1: X-rays of a normal hip joint (left) and one affected by osteoarthritis (right).

Genes can affect disease differently depending on one’s ethnicity, concludes a team of international researchers reporting in the July 2007 issue of Human Molecular Genetics1.

It has been long known that some diseases have genetic risk factors that determine whether a person is susceptible. Because some diseases have many genetic factors associated with them, they are called ‘polygenic’ diseases. The greater the number of genes associated with a disease, the more difficult it can be to show a causal link between one specific gene and disease.

Led by Shiro Ikegawa at the SNP Research Center of RIKEN in Yokohama, the team analyzed published studies that showed inconsistent results on the importance of one particular gene in the susceptibility to osteoarthritis (OA) (Fig. 1). The gene in question codes for a protein called asporin, which accumulates in arthritic joints.

A previous study positively linked OA of the knee and a specific change in asporin in a population of Japanese people; the association was replicated in a separate study of OA of the knee and in another study of OA of the hip. However, other studies of people from the United Kingdom, Greece, China and Spain found either positive or insignificant associations of genetics changes in asporin and OA in the knee and/or hip.

With the hope of shedding light on these inconsistencies, Ikegawa’s team performed a type of statistical analysis called ‘meta-analysis’, which takes the information from separate studies and analyzes it with special types of statistical formulae that can factor out confounding factors present in each individual study.

“Meta-analyses can solve the problem of inconsistent studies by considering and compensating for the differences of the observers [the researcher],” says Ikegawa. Meta-analyses remove types of bias inherent in the complex and unpredictable nature of studying human diseases.

From their analyses, Ikegawa and team concluded that the genetic link between asporin and knee OA has global relevance and that while asporin is clearly the susceptibility gene with a modest effect in Asians, it is less so for Europeans.

Commenting on their success in achieving these results and developing a center of international collaboration in this field, Ikegawa says: “The road to collaboration was long and winding but the world is one, and so it should be for science and patients in every aspect.” Such collaboration will no doubt be required to help solve other puzzling mysteries that link genes to human disease.


  1. Nakamura, T., Shi, D., Tzetis, M., Rodriguez-Lopez, J., Miyamoto, Y., Tsezou, A., Gonzalez, A., Jiang, Q., Kamatani, N., Loughlin, J. & Ikegawa, S. Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Human Molecular Genetics 14, 1676–1681 (2007). (Link)