Genome-wide association analysis of anti-TNF-α treatment response in Chinese patients with psoriasis.

TNF-α inhibitors are effective biological agents for treating psoriasis, but the treatment responses differ across patients. This study aimed to identify genetic biomarkers of anti-TNF-α response in Chinese psoriasis patients using a genome-wide association approach. We recruited two independent cohorts of Chinese psoriasis patients administered etanercept biosimilar (with or without methotrexate). We identified 61 and 87 good responders (PASI improvement ≥75%), 19 and 10 poor responders (PASI improvement <50%) after 24 weeks treatment in the two cohorts, respectively. Then we performed genome-wide association studies (GWAS) on anti-TNF-α response in each cohort independently, followed by a fixed-effects inverse-variance meta-analysis in the 148 good and 29 poor responders. We tested genetic associations with >3 million genetic variants in either cohort. Meta-analysis identified significant associations within seven loci at < 10, which also showed consistent association evidence in the two cohorts. These seven loci include rs2431355 (OR = 6.65, = 4.46 × 10, on 5q13.3), rs11801616 (OR = 0.11, = 1.75 × 10, on 1p35.2), rs3754679 (OR = 0.17, = 7.71 × 10, on 2q11.2), rs13166823 (OR = 0.09, = 3.71 × 10, on 5q31.1), rs10220768 (OR = 5.49, = 1.48 × 10, on 15q11.2), rs4796752 (OR = 5.56, = 1.49 × 10, on 17q21.2), and rs13045590 (OR = 0.08, = 9.67 × 10, on 20q13.3). Of the seven SNPs, six SNPs showed significant eQTL effect ( < 1 × 10) for several genes in multiple tissues. These results suggest novel biological mechanisms and potential biomarkers for the response to anti-TNF therapies. These findings warrant further validation.