Page 51 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk

HOW DOES ESTABLISHED RHEUMATOID ARTHRITIS DEVELOP
models for RA, some including environmental factors, are presented in Table 1. In the case of multiple publications from one cohort, only the last publication is shown.
In summary, these studies show ORs of different models of around 2.0, and a wide 3 variation of area under the curves (AUC) from a low value of 0.54 to a high value of
0.89 (with the highest values also including clinical parameters). A relatively high specificity for identifying individuals at risk (75-90%) is unfortunately accompanied
by a very low sensitivity (30-45%). Therefore, apart from the disadvantage of its high cost, genetic risk prediction is thus still not precise enough to be used in current clinical practice, even though more and more genetic loci are being discovered. However, a recent study shows that a GRS plus environmental factors in family members of RA patients provides enough discrimination to enable the selection of high-risk subjects for intervention studies(13). To support future research, Nagai et al. have made the open access database “RAvariome,” which was developed to list all RA-associated genetic variants and check reproducibility over different ethnicities(14). Their website (http:// hinv.jp/hinv/rav/) also provides a “genetic risk predictor,” which gives the lifetime risk on developing RA per individual. Unfortunately, as with the different GRS, the timing of RA development cannot be predicted by using this database.
Table 1. Prediction models for development of rheumatoid arthritis using genetic, clinical and behavioral (smoking) data
Reference Cohort; variables
Numbers
570 UA
1552 ACPA+RA
1504 con- trols
WTCCC/ UKRAGG: 1516/2623 RA 1647/1500 controls
Results
Model with genetic loci combined: AUC 0.54 (CI: 0.48-0.59)
Genetic loci and clinical parameter: AUC 0.89 (CI: 0.86-0.95)
European ancestry: AUC 0.71 (CI: 0.68-0.73) African ancestry:
AUC 0.63 (CI: 0.56-0.70) East Asian ancestry: AUC 0.74 (CI: 0.59-0.89) Hispanic ancestry:
AUC 0.66 (CI: 0.56-0.76)
HLA-SNP model
WTCCC: AUC 0.80 (CI: 0.78-0.81) UKRAGG: AUC 0.76 (CI: 0.72-0.79) HLA-SNP-smoking model
WTCCC: AUC 0.84 (CI: 0.81-0.87) UKRAGG: AUC 0.86 (CI: 0.80-0.91)
table continues
van der Helm
2010(15)
Kurree- man
2011(9)
Scott 2013(16)
Early arthritis cohort, the Netherlands
Genetic loci: HLA-DRB1 SE alleles, 11 SNPs
Clinical parameter: smoking
EHR cohort, USA
Genetic loci: 1 HLA allele, 29 SNPs
WTCCC and UKRAGG, UK
Genetic loci: 25 HLA alleles, 31 SNPs
Clinical parameter: smoking
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