A longitudinal genome-wide association study of anti-tumor necrosis factor response among Japanese patients with rheumatoid arthritis

Arthritis Research & Therapy
Kyoko HonneDamini Jawaheer

Abstract

Studies of Caucasian patients with rheumatoid arthritis (RA) to identify genetic biomarkers of anti-tumor necrosis factor (TNF) response have used response at a single time point as the phenotype with which single nucleotide polymorphism (SNP) associations have been tested. The findings have been inconsistent across studies. Among Japanese patients, only a few SNPs have been investigated. We report here the first genome-wide association study (GWAS) to identify genetic biomarkers of anti-TNF response among Japanese RA patients, using response at 2 time-points for a more reliable clinical phenotype over time. Disease Activity Scores based on 28 joint counts (DAS28) were assessed at baseline (before initial therapy), and after 3 and 6 months in 487 Japanese RA patients starting anti-TNF therapy for the first time or switching to a new anti-TNF agent. A genome-wide panel of SNPs was genotyped and additional SNPs were imputed. Using change in DAS28 scores from baseline at both 3 (ΔDAS-3) and 6 months (ΔDAS-6) as the response phenotype, a longitudinal genome-wide association analysis was conducted using generalized estimating equations (GEE) models, adjusting for baseline DAS28, treatment duration, type of anti-TNF agent and concomi...Continue Reading

References

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Citations

Aug 25, 2017·Pharmacogenomics·Nisha NairAnne Barton
Dec 12, 2018·Annals of the Rheumatic Diseases·Yukinori OkadaKazuhiko Yamamoto
May 8, 2018·PloS One·Rosario Lopez-RodriguezAntonio Gonzalez
Dec 12, 2020·Pharmacogenomics·Bianca Jc van den Bosch, Marieke Jh Coenen
Feb 25, 2021·Expert Review of Clinical Immunology·Ikram MezghicheElisabetta Bianchi

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Methods Mentioned

BETA
genotyping

Software Mentioned

STATA
PLINK
GTOOL
EIGENSTRAT
ShapeIT
Impute2
Illumina BeadStudio

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