A Genome-Wide Association Study of Copy Number Variations Identifies the Deletion Associated with Efficacy of TNF-Alpha Blocker Therapy in Korean Patients with Rheumatoid Arthritis
DC Field | Value | Language |
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dc.contributor.author | Gu, Ki-Nam | - |
dc.contributor.author | Bang, So-Young | - |
dc.contributor.author | Lee, Hye-Soon | - |
dc.contributor.author | Park, Youngho | - |
dc.contributor.author | Kang, Juyeon | - |
dc.contributor.author | Kim, Ji-Soong | - |
dc.contributor.author | Nam, Bora | - |
dc.contributor.author | Yoo, Hyun-Seung | - |
dc.contributor.author | Shin, Jung-Min | - |
dc.contributor.author | Lee, Yeon-Kyung | - |
dc.contributor.author | Lee, Tae-Han | - |
dc.contributor.author | Chun, Sehwan | - |
dc.contributor.author | Cho, Soo-Kyung | - |
dc.contributor.author | Choi, Chan-Bum | - |
dc.contributor.author | Sung, Yoon-Kyoung | - |
dc.contributor.author | Kim, Tae-Hwan | - |
dc.contributor.author | Jun, Jae-Bum | - |
dc.contributor.author | Yoo, DaeHyun | - |
dc.contributor.author | Kim, Kwangwoo | - |
dc.contributor.author | Bae, Sang-Cheol | - |
dc.date.accessioned | 2021-08-02T10:32:22Z | - |
dc.date.available | 2021-08-02T10:32:22Z | - |
dc.date.created | 2021-06-02 | - |
dc.date.issued | 2019-11-10 | - |
dc.identifier.issn | 2326-5191 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/12134 | - |
dc.description.abstract | Background/Purpose: Copy number variation (CNV) is the most common structural variation defined as large ( >1 kb) genomic deletions and duplications and could yield a high impact on various traits including drug response. In this study, we performed a genome-wide association studies (GWAS) of CNV to investigate the efficacy of treatment with TNF-α blockers in patients with rheumatoid arthritis (RA). Methods: The study was conducted in 357 Korean RA patients treated with TNF-α blockers. All the study subjects were classified into non-responders and responders based on the change in disease activity indexes at 6 months according to the EULAR response criteria. A multivariate logistic regression analysis performed to fit the response to TNF-α blocker therapy with a CNV adjusting for the top 10 genetic principal components, body mass index, gender, baseline disease activity, and methotrexate use. Results: The study subjects had 319 common CNVs with the frequency of abnormal-copy carrier ≥ 5% in autosomes and varied in their responses to TNF-α blockers with a wide range of 6-month changes in disease activity indexes. The CNV-response association analysis revealed that the copy number at 2q14.3 was associated with response to TNF-α blockers therapy in the patients with RA (P ≤ 3.2 x 10-4) at a false discovery rate (FDR) threshold of 5%. The loss of copy number in the identified CNV was significantly more in the non-responders than in the responders (7.3 ≤ odds ratio ≤ 8.5), indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the experimentally validated binding sites of two transcription factors, MAFF and MAFK. Conclusion: This study conducted the first genome-wide CNV analysis to identify which structural variations associated with the varied response to the TNF-α blocker therapy. Here, we identified a novel CNV that explained a proportion of the inter-individual variance in efficacy of biologics based on the common response criteria. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.title | A Genome-Wide Association Study of Copy Number Variations Identifies the Deletion Associated with Efficacy of TNF-Alpha Blocker Therapy in Korean Patients with Rheumatoid Arthritis | - |
dc.type | Conference | - |
dc.contributor.affiliatedAuthor | Bang, So-Young | - |
dc.contributor.affiliatedAuthor | Lee, Hye-Soon | - |
dc.contributor.affiliatedAuthor | Cho, Soo-Kyung | - |
dc.contributor.affiliatedAuthor | Choi, Chan-Bum | - |
dc.contributor.affiliatedAuthor | Sung, Yoon-Kyoung | - |
dc.contributor.affiliatedAuthor | Kim, Tae-Hwan | - |
dc.contributor.affiliatedAuthor | Jun, Jae-Bum | - |
dc.contributor.affiliatedAuthor | Yoo, DaeHyun | - |
dc.contributor.affiliatedAuthor | Bae, Sang-Cheol | - |
dc.identifier.wosid | 000507466903311 | - |
dc.identifier.bibliographicCitation | 2019 ACR/ARP Annual Meeting | - |
dc.relation.isPartOf | 2019 ACR/ARP Annual Meeting | - |
dc.relation.isPartOf | ARTHRITIS & RHEUMATOLOGY | - |
dc.citation.title | 2019 ACR/ARP Annual Meeting | - |
dc.citation.conferencePlace | US | - |
dc.citation.conferenceDate | 2019-11-10 | - |
dc.type.rims | CONF | - |
dc.description.journalClass | 1 | - |
dc.identifier.url | https://acrabstracts.org/abstract/a-genome-wide-association-study-of-copy-number-variations-identifies-the-deletion-associated-with-efficacy-of-tnf-alpha-blocker-therapy-in-korean-patients-with-rheumatoid-arthritis/ | - |
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