Phenome-Wide Association Study of Autoantibodies to Citrullinated and Noncitrullinated Epitopes in Rheumatoid Arthritis

被引：27

作者：

Liao, Katherine P. ^{[1
,2
]}

Sparks, Jeffrey A. ^{[1
,2
]}

Hejblum, Boris P. ^{[3
]}

Kuo, I-Hsin ^{[1
,2
,4
]}

Cui, Jing ^{[1
,2
]}

Lahey, Lauren J. ^{[5
,6
]}

Cagan, Andrew ^{[7
]}

Gainer, Vivian S. ^{[7
]}

Liu, Weidong ^{[8
]}

Cai, T. Tony ^{[9
]}

Sokolove, Jeremy ^{[5
,6
]}

Cai, Tianxi

机构：

[1] Brigham & Womens Hosp, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA USA

[3] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[4] Biogen, Cambridge, MA USA

[5] VA Palo Alto Healthcare Syst, Palo Alto, CA USA

[6] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA

[7] Partners Healthcare, Charlestown, MA USA

[8] Shanghai Jiao Tong Univ, Shanghai, Peoples R China

[9] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA

来源：

ARTHRITIS & RHEUMATOLOGY | 2017年 / 69卷 / 04期

关键词：

ELECTRONIC MEDICAL-RECORDS; FALSE DISCOVERY RATE; HEALTH RECORDS; DISEASE; RISK;

D O I：

10.1002/art.39974

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. Patients with rheumatoid arthritis (RA) develop autoantibodies against a spectrum of antigens, but the clinical significance of these autoantibodies is unclear. Using a phenome-wide association study (PheWAS) approach, we examined the association between autoantibodies and clinical subphenotypes of RA. Methods. This study was conducted in a cohort of RA patients identified from the electronic medical records (EMRs) of 2 tertiary care centers. Using a published multiplex bead assay, we measured 36 autoantibodies targeting epitopes implicated in RA. We extracted all International Classification of Diseases, Ninth Revision (ICD-9) codes for each subject and grouped them into disease categories (PheWAS codes), using a published method. We tested for the association of each autoantibody (grouped by the targeted protein) with PheWAS codes. To determine significant associations (at a false discovery rate [FDR] of <= 0.1), we reviewed the medical records of 50 patients with each PheWAS code to determine positive predictive values ( PPVs). Results. We studied 1,006 RA patients; the mean +/- SD age of the patients was 61.0 +/- 12.9 years, and 79.0% were female. A total of 3,568 unique ICD-9 codes were grouped into 625 PheWAS codes; the 206 PheWAS codes with a prevalence of >= 3% were studied. Using the PheWAS method, we identified 24 significant associations of auto-antibodies to epitopes at an FDR of <= 0.1. The associations that were strongest and had the highest PPV for the PheWAS code were autoantibodies against fibronectin and obesity ( P = 6.1 x 10(-4), PPV 100%), and that between fibrinogen and pneumonopathy ( P = 2.7 x 10(-4), PPV 96%). Pneumonopathy codes included diagnoses for cryptogenic organizing pneumonia and obliterative bronchiolitis. Conclusion. We demonstrated application of a bio-informatics method, the PheWAS, to screen for the clinical significance of RA-related autoantibodies. Using the PheWAS approach, we identified potentially significant links between variations in the levels of autoantibodies and comorbidities of interest in RA.

引用

页码：742 / 749

页数：8

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