Database (Oxford). 2013 Oct 23;2013(0):bat073. doi: 10.1093/database/bat073. Print 2013.
RAvariome: a genetic risk variants database for rheumatoid arthritis based on assessment of reproducibility between or within human populations.
SourceDepartment of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan and Data Management and Integration Team, Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo 135-0064, Japan.
Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease of the joints and is caused by both genetic and environmental factors. In the past six years, genome-wide association studies (GWASs) have identified many risk variants associated with RA. However, not all associations reported from GWASs are reproduced when tested in follow-up studies. To establish a reliable set of RA risk variants, we systematically classified common variants identified in GWASs by the degree of reproducibility among independent studies. We collected comprehensive genetic associations from 90 papers of GWASs and meta-analysis. The genetic variants were assessed according to the statistical significance and reproducibility between or within nine geographical populations. As a result, 82 and 19 single nucleotide polymorphisms (SNPs) were confirmed as intra- and inter-population-reproduced variants, respectively. Interestingly, majority of the intra-population-reproduced variants from European and East Asian populations were not common in two populations, but their nearby genes appeared to be the components of common pathways. Furthermore, a tool to predict the individual's genetic risk of RA was developed to facilitate personalized medicine and preventive health care. For further clinical researches, the list of reliable genetic variants of RA and the genetic risk prediction tool are provided by open access database RAvariome. Database URL: http://hinv.jp/hinv/rav/
- [PubMed - in process]
The flowchart for the assessment of association results from articles. From comprehensive search by NHGRI Genome-Wide Association catalog, HuGE Navigator and PubMedScan, 153 literatures were collected. In all, 7730 associations were collected from 90 literatures by manual screening and reading. The associations were grouped into the nine geographical populations based on sample information. A total of 6740 associations (6614 unique genetic variants) were chosen as representative associations of the variants in either population. In all, 5444 representative associations (5405 unique variants) did not reach significance level, and 1296 representative associations (1274 unique variants) were statistically significant and remained for further analysis. Forty representative associations of 19 variants were reproduced between different populations, and associations of 82 variants were reproduced in the particular population. The confirmed variants were used to predict genetic risk of RA based on individual’s genotype. The data can be view and downloaded from the web database RAvariome.
RAvariome: a genetic risk variants database for rheumatoid arthritis based on assessment of reproducibility between or within human populations
Database (Oxford). 2013;2013:bat073.