A Systems Genetics Approach Provides a Bridge from Discovered Genetic Variants to Biological Pathways in Rheumatoid Arthritis
2011

Understanding Genetic Factors in Rheumatoid Arthritis

Sample size: 2787 publication 10 minutes Evidence: moderate

Author Information

Author(s): Nakaoka Hirofumi, Cui Tailin, Tajima Atsushi, Oka Akira, Mitsunaga Shigeki, Kashiwase Koichi, Homma Yasuhiko, Sato Shinji, Suzuki Yasuo, Inoko Hidetoshi, Inoue Ituro

Primary Institution: National Institute of Genetics, Tokai University, and other institutions in Japan

Hypothesis

Can a systems genetics approach improve our understanding of the genetic architecture of rheumatoid arthritis?

Conclusion

The systems genetics approach is useful for identifying genetic risk factors and biological pathways related to rheumatoid arthritis.

Supporting Evidence

  • 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in the study.
  • The area under the curve for the genetic risk score was 68.4%.
  • Significant associations were found for several genetic variants.
  • The predictive ability improved for seropositive RA patients.
  • Simulation studies indicated the need for more genetic loci to improve prediction accuracy.
  • Network analysis identified functional modules relevant to RA etiology.
  • ZAP70 was prioritized as a key gene in the study.

Takeaway

Researchers studied genes related to rheumatoid arthritis to find out how they work together and how they can help predict the disease.

Methodology

The study involved genome-wide association studies (GWAS) and case-control analysis of genetic variants in rheumatoid arthritis patients.

Potential Biases

Potential bias due to the reliance on previously published studies and the limitations of the databases searched.

Limitations

The study's electronic database search was conducted a year prior, and newer genetic findings may not have been included.

Participant Demographics

1,287 rheumatoid arthritis cases and 1,500 controls of Japanese origin.

Statistical Information

P-Value

p<0.05

Confidence Interval

95% CI, 66.4 to 70.4%

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0025389

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