Exome Sequencing of Chinese Patients With Anticitrullinated Protein Antibody-Positive Rheumatoid Arthritis in Singapore.

IF 3.6 2区医学 Q2 RHEUMATOLOGY

Journal of Rheumatology Pub Date : 2025-01-15 DOI:10.3899/jrheum.2024-0140

Khai Pang Leong, Mei Yun Yong, Ee Tzun Koh, Peter Pak Moon Cheung, Manjari Lahiri, Chin Teck Ng, Chia Mun Woo, Liuh Ling Goh, Sandy Hong Hong Lim, Preeti Dhanasekaran, Grace Yee May Cheah, Justina Wei Lyn Tan, Wenchao Hu, Mei Ling Chong, Vikrant Kumar, Sonia Davila

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引用次数: 0

Abstract

Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies. To investigate the genetic predisposition of Chinese patients to anticitrullinated protein antibody (ACPA)-positive RA, we carried out an exome sequencing study.

Methods: Patients were recruited from 3 major public hospitals in Singapore: Tan Tock Seng Hospital (TTSH), Singapore General Hospital, and the National University Hospital. Controls came from an established exome collection and from the TTSH Health Control Biobank. All the participants were of Chinese descent. We performed whole-exome sequencing (WES) in 595 ACPA-positive patients with RA and 1281 controls and validated the candidate variants by genotyping 795 RA cases and 600 controls.

Results: The discovery cohort yielded 73 susceptibility single-nucleotide variants (SNVs) that reached statistical significance. In the validation study with an independent cohort, 2 SNVs remained significant: PCNXL4 (P = 1.50 × 10^-5) and DHRS7 (P = 6.02 × 10^-5). The majority of known susceptibility foci were not captured by exome sequencing.

Conclusion: In this WES study of ACPA-positive RA in Chinese patients, we discovered 2 new variants in PCNXL4 and DHRS7 associated with risk for RA.

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新加坡华人抗瓜氨酸化蛋白抗体阳性类风湿关节炎患者的外显子组测序。

目的：通过全基因组关联研究（GWAS）发现了130多个类风湿关节炎（RA）的易感位点。为了研究中国人抗环瓜氨酸肽抗体阳性RA的遗传易感性，我们进行了外显子组测序研究。方法：患者来自新加坡三家主要公立医院：陈笃生医院（TTSH）、新加坡总医院和国立大学卫生系统。对照来自已建立的外显子组收集和TTSH健康控制生物库。所有的参与者都是华裔。我们对595例acpa阳性RA患者和1281例对照者进行了全外显子组测序（WES），并通过对795例RA患者和600例对照者进行基因分型验证了候选变异。结果：发现队列产生73个具有统计学意义的敏感性snv。在独立队列验证研究中，两个snv仍然显著：PCNXL4 （p值1.50x10-5）和DHRS7 （p值6.02x10 -5）。大多数已知的易感灶没有被外显子组测序捕获。结论：在中国acpa阳性RA患者的WES研究中，我们发现了PCNXL4和DHRS7两种与疾病风险相关的新变异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Rheumatology 医学-风湿病学

CiteScore

6.50

自引率

5.10%

发文量

285

审稿时长

1 months

期刊介绍： The Journal of Rheumatology is a monthly international serial edited by Earl D. Silverman. The Journal features research articles on clinical subjects from scientists working in rheumatology and related fields, as well as proceedings of meetings as supplements to regular issues. Highlights of our 41 years serving Rheumatology include: groundbreaking and provocative editorials such as "Inverting the Pyramid," renowned Pediatric Rheumatology, proceedings of OMERACT and the Canadian Rheumatology Association, Cochrane Musculoskeletal Reviews, and supplements on emerging therapies.