Predicting the progression of rheumatoid arthritis

Date:
March 7, 2022
Source:
Tokyo Medical and Dental University
Summary:
Researchers evaluated the ability of a polygenic risk score
constructed from a genome-wide association study of rheumatoid
arthritis susceptibility to predict radiographic progression,
which is indicative of structural joint damage in individuals with
rheumatoid arthritis. The research team identified an association
between the polygenic risk score and radiographic progression,
an observation that was pronounced in people with a younger age
of onset of rheumatoid arthritis.



FULL STORY ========================================================================== Predicting the future may be beyond our grasp, but what about predicting disease progression? Researchers in Japan have delved into the human
genome to investigate a predictive tool for the progression of rheumatoid arthritis (RA), an inflammatory autoimmune disease showing progressive
joint damage.


==========================================================================
In a new study published in Arthritis & Rheumatology, researchers led by
Tokyo Medical and Dental University (TMDU) used data from a genome-wide association study (GWAS) of RA susceptibility to construct a polygenic
risk score (PRS).

They evaluated the PRS's ability to predict radiographic progression -
- progressive anatomical damage assessed by radiographic imaging --
in individuals with RA.

In a GWAS, genomic analysis of a group of individuals is performed to
identify genetic variants that may be associated with a certain trait
or disease. A PRS can be generated from a GWAS dataset and represents an individual's risk of developing a specific disease based on a summation of
the genetic variants associated with that disease. Previous studies have identified genetic factors associated with radiographic progression of RA, including the presence of anti- citrullinated protein antibodies (ACPAs)
and variants located in the human leukocyte antigen (HLA) region of the
human chromosome that contribute to regulating the immune system. However,
the predictive accuracy of these factors is not robust. Therefore,
the TMDU-led research team set out to evaluate the ability of the PRS
to predict radiographic progression in people with RA.

"We generated the PRS using summary statistics from a GWAS analysis of
RA susceptibility and evaluated radiographic joint damage retrospectively
from patient medical records," explains lead author Suguru Honda.

The researchers then conducted statistical analysis to assess whether
there is an association between PRS and severity of radiographic
progression.

Additionally, the research team performed a multivariable analysis
to evaluate the association between radiographic progression and the combination of PRS and other factors such as sex, age of onset, and
presence of ACPAs or HLA region variants.

"Our analyses revealed an association between PRS and radiographic progression," says senior author Yuta Kochi. "The PRS significantly
differed between severe and non-severe progression groups."
The researchers found that patients with a higher PRS had a
higher risk of severe progression, particularly among younger-onset individuals. Furthermore, the multivariable analysis revealed that the association of the PRS with radiographic progression is not influenced by
other clinical factors. Thus, PRS's could be used to predict radiographic progression. These findings highlight the potential applications of
genetic profiling in the development of precision medicine approaches
for the treatment of RA.

========================================================================== Story Source: Materials provided by
Tokyo_Medical_and_Dental_University. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Suguru Honda, Katsunori Ikari, Koichiro Yano, Chikashi Terao, Eiichi
Tanaka, Masayoshi Harigai, Yuta Kochi. Polygenic risk scores are
associated with radiographic progression in patients with rheumatoid
arthritis. Arthritis & Rheumatology, 2022; DOI: 10.1002/art.42051 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220307132042.htm

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