You are here

Sci Transl Med DOI:10.1126/scitranslmed.aay1548

Using genetics to prioritize diagnoses for rheumatology outpatients with inflammatory arthritis.

Publication TypeJournal Article
Year of Publication2020
AuthorsKnevel, R, le Cessie, S, Terao, CC, Slowikowski, K, Cui, J, Huizinga, TWJ, Costenbader, KH, Liao, KP, Karlson, EW, Raychaudhuri, S
JournalSci Transl Med
Date Published2020 May 27

It is challenging to quickly diagnose slowly progressing diseases. To prioritize multiple related diagnoses, we developed G-PROB (Genetic Probability tool) to calculate the probability of different diseases for a patient using genetic risk scores. We tested G-PROB for inflammatory arthritis-causing diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathy, psoriatic arthritis, and gout). After validating on simulated data, we tested G-PROB in three cohorts: 1211 patients identified by International Classification of Diseases (ICD) codes within the eMERGE database, 245 patients identified through ICD codes and medical record review within the Partners Biobank, and 243 patients first presenting with unexplained inflammatory arthritis and with final diagnoses by record review within the Partners Biobank. Calibration of G-probabilities with disease status was high, with regression coefficients from 0.90 to 1.08 (1.00 is ideal). G-probabilities discriminated true diagnoses across the three cohorts with pooled areas under the curve (95% CI) of 0.69 (0.67 to 0.71), 0.81 (0.76 to 0.84), and 0.84 (0.81 to 0.86), respectively. For all patients, at least one disease could be ruled out, and in 45% of patients, a likely diagnosis was identified with a 64% positive predictive value. In 35% of cases, the clinician's initial diagnosis was incorrect. Initial clinical diagnosis explained 39% of the variance in final disease, which improved to 51% (


Alternate JournalSci Transl Med
PubMed ID32461333