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Arthritis Rheumatol. 2016 Sep 2. doi: 10.1002/art.39851. [Epub ahead of print]
Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association between Seronegative Disease and Fibromyalgia.
Doss J1, Mo H2, Carroll RJ3, Crofford LJ4, Denny JC5.
Author information
Abstract
OBJECTIVE:
The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA.
METHODS:
A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). We tested EHR-derived phenotypes using PheWAS comparing seropositive RA against seronegative RA, yielding disease associations. PheWAS was also performed on RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed and fibromyalgia was specifically evaluated using a validated algorithm.
RESULTS:
There were 2199 individuals identified with RA and either RF or ACPA testing. Of these, 1382 (63%) were seropositive. Seronegative RA was associated with "Myalgia and Myositis" (odds ratio [OR] 2.1, P=3.7x10-10 ) and back pain. A manual record review showed 80% of Myalgia and Myositis codes were used for fibromyalgia, and follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR=1.8, P=4.0x10-6 ). Seropositive RA was associated with Chronic Airway Obstruction (OR=2.2, P=1.4x10-4 ) and tobacco use (OR=2.2, P=7.0x10-4 ).
CONCLUSION:
This PheWAS in RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity with chronic airway obstruction and seropositivity with tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. This article is protected by copyright. All rights reserved.
Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association between Seronegative Disease and Fibromyalgia.
Doss J1, Mo H2, Carroll RJ3, Crofford LJ4, Denny JC5.
Author information
Abstract
OBJECTIVE:
The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA.
METHODS:
A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). We tested EHR-derived phenotypes using PheWAS comparing seropositive RA against seronegative RA, yielding disease associations. PheWAS was also performed on RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed and fibromyalgia was specifically evaluated using a validated algorithm.
RESULTS:
There were 2199 individuals identified with RA and either RF or ACPA testing. Of these, 1382 (63%) were seropositive. Seronegative RA was associated with "Myalgia and Myositis" (odds ratio [OR] 2.1, P=3.7x10-10 ) and back pain. A manual record review showed 80% of Myalgia and Myositis codes were used for fibromyalgia, and follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR=1.8, P=4.0x10-6 ). Seropositive RA was associated with Chronic Airway Obstruction (OR=2.2, P=1.4x10-4 ) and tobacco use (OR=2.2, P=7.0x10-4 ).
CONCLUSION:
This PheWAS in RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity with chronic airway obstruction and seropositivity with tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. This article is protected by copyright. All rights reserved.
