Comprehensive analysis of treatment response phenotypes in rheumatoid arthritis for pharmacogenetic studies

Arthritis Research & Therapy
Kristopher A StandishNicholas J Schork

Abstract

An individual patient's response to a particular drug is influenced by multiple factors, which may include genetic predisposition. Pharmacogenetic studies attempt to discover and estimate the contributions of genetic variants to the variability in response to a drug treatment. The task of identifying the genetic contribution is often complicated by response phenotypes that are based on imprecise or subjective clinical observations. Because the success of a pharmacogenetic study depends on the analysis of a heritable phenotype, it is important to identify phenotypes with a significant heritable component to ensure reliable and reproducible results in subsequent genetic association studies. We retrospectively analyzed data collected from 436 rheumatoid arthritis patients treated with golimumab during the phase III GO-FURTHER study. We investigated the reliability of several potential response outcomes after golimumab treatment. Using whole-genome sequencing of the clinical trial cohort, we estimated the heritability of each potential outcome measure. We further performed a longitudinal analysis of the clinical data to estimate variability of outcome measures over time and the degree to which each response metric could be confound...Continue Reading

References

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Methods Mentioned

BETA
genotyping
ESR

Clinical Trials Mentioned

NCT00973479

Software Mentioned

R suite
GCTA
wide Complex Trait Analysis toolkit ( GCTA )
Genome

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