ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2697

Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia

Jayanth Doss1, Huan Mo2, Leslie J. Crofford1 and Joshua C. Denny2, 1Rheumatology, Vanderbilt University School of Medicine, Nashville, TN, 2Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: The differences between seronegative and seropositive rheumatoid
arthritis (RA) have not been widely reported. We performed an electronic health
record (EHR)-based phenome-wide association study (PheWAS) to identify disease associations
that differ between seropositive and seronegative RA.

Methods:   A validated algorithm identified RA subjects from the
de-identified EHR (1). Serotypes were determined by values of rheumatoid factor
(RF) and anti-cyclic citrullinated peptide antibody (ACPA). A PheWAS uses
logistic regression to identify ICD9 codes that are more likely to be present
in one group of patients versus another. A PheWAS comparing seropositive and
seronegative patients was performed and identified disease associations (i.e.
ICD9 codes) for each serotype. Following PheWAS, select disease associations
were manually reviewed and fibromyalgia was specifically evaluated using a
validated algorithm.

Results:   A total of 2199 individuals were identified with RA and with
serologic testing. Of these, 1382 (63%) were seropositive. Seronegative RA was
associated with “Myalgia and Myositis” (odds ratio [OR] 2.1, P=3.7×10-10)
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=4.0×10-6). Seropositive RA was associated with Chronic Airway
Obstruction (OR=2.2, P=1.4×10-4), tobacco use (OR=2.1, P=3.8×10-4),
and other pulmonary phenotypes.

Conclusion:   This PheWAS study in RA patients identifies a strong
association between seronegativity and fibromyalgia.  It also replicates a
well-known association between seropositivity and chronic airway obstruction
related to tobacco use. These findings demonstrate the utility of the PheWAS
approach to discover novel phenotype associations within different subgroups of
a disease.

Table 1

 

All Patients (n = 2199)

Seropositive (n = 1382)

Seronegative (n = 817)

Demographic Characteristics

 

 

 

Age, mean ± SD years

52.1 ± 14.5

53.17 ± 13.4

51.7 ± 14

Sex, no. (%) female

1669 (76)

1012 (73)

657 (80)

Race, no. (%)

 

 

 

White

1711 (78)

1063 (77)

648 (79)

Black

176 (8)

127 (9)

50 (6)

Other

22 (1)

14 (1)

7 (1)

Unknown

290 (13)

178 (13)

112 (14)

Electronic Health Record (EHR) Encounter Data

 

 

 

Median EHR time in years (IQR)

8 (5 – 14)

8 (5 – 13)

8 (5 – 14)

Median EHR time with RA ICD9 Codes in years (IQR)

6 (3 – 8)

6 (3 – 9)

5 (3 – 8)

Median EHR Billing Encounters (IQR)

29 (14 – 60)

29 (14 – 60)

29 (14 – 60)

Median EHR Billing Encounters with RA ICD9 Codes (IQR)

16 (8 – 28)

17 (8 – 29)

14 (7 – 26)

 

 

Table 2. PheWAS results adjusted for age and sex

 

Cases

Controls

OR

CI (95%)

p

Associations favoring seronegative RA 

Myalgia and Myositis *

346

1642

2.1

1.7 – 2.7

3.7 x 10-10

Spondylosis and allied disorders

104

1725

2.2

1.4 – 3.2

1.7 x 10-4

Spondylosis without myelopathy

96

1725

2.2

1.4 – 3.3

2.5 x 10-4

Intervertebral disc disorders

191

1725

1.7

1.3 – 2.3

5.2 x 10-4

Internal Derangement of Knee

38

2032

3.4

1.7 – 6.8

5.3 x 10-4

Polymyalgia Rheumatica

35

2140

3.2

1.6 – 6.6

1.1 x 10-3

Spinal Stenosis

102

1725

1.9

1.3 – 2.9

1.7 x 10-3

 

 

 

 

 

 

Associations favoring seropositive RA

Chronic Airway Obstruction

149

1842

2.2

1.5 – 3.4

1.4 x 10-4

Tobacco Use Disorder

143

1885

2.1

1.4 – 3.1

3.8 x 10-4

Staphylococcus Infection

32

2051

5.7

1.7 – 18.8

4.3 x 10-3

Chronic Ulcer of Skin

51

2104

2.8

1.3 – 5.8

5.8 x 10-3

Diseases of Respiratory System

29

2112

7.5

1.8 – 31.6

6.2 x 10-3

Post-Inflammatory Pulm Fibrosis

65

1880

2.4

1.3 – 4.4

6.3 x 10-3

Symptoms Involving Resp System

26

2138

6.6

1.6 – 28.1

1.1 x 10-2

* p-value reaches Bonferroni
threshold of 1.3 x 10-4

 

Figure 1.  PheWAS Manhattan
plots of RA patients comparing seropositive and seronegative phenotypes


 

References

1.    Carroll
RJ, et al. Portability of an algorithm to identify rheumatoid arthritis in
electronic health records. J Am Med Inform Assoc JAMIA. 2012 Jun;19(e1):e162–9.

Disclosure: J. Doss, None; H. Mo, None; L. J. Crofford, None; J. C. Denny, None.

To cite this abstract in AMA style:

Doss J, Mo H, Crofford LJ, Denny JC. Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/phenome-wide-association-study-of-rheumatoid-arthritis-subgroups-identifies-association-between-seronegative-disease-and-fibromyalgia/. Accessed .

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