Hanna W van Steenbergen1, Roula Tsonaka2, Tom Wj Huizinga1, Saskia le Cessie3, Annette Hm van der Helm-van Mil1. 1. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. 2. Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. 3. Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
BACKGROUND: The severity of radiologic progression is variable between rheumatoid arthritis (RA) patients. Recently, several genetic severity variants have been identified and were replicated, these belong to 12 loci. This study determined the contribution of the identified genetic factors to the explained variance in radiologic progression and whether genetic factors, in addition to traditional risk factors, improve the accuracy of predicting the severity of radiologic progression. METHODS: 426 early RA patients with yearly radiologic follow-up were studied. The main outcome measure was the progression in Sharp-van der Heijde score (SHS) over 6 years, assessed as continuous outcome or categorised in no/little, moderate or severe progression. Assessed were improved fit of a linear mixed model analysis on serial radiographs, R(2) using linear regression analyses, C-statistic and the net proportion of patients that was additionally correctly classified when adding genetic risk factors to a model consisting of traditional risk factors. RESULTS: The genetic factors together explained 12-18%. When added to a model including traditional factors and treatment effects, the genetic factors additionally explained 3-7% of the variance (p value R(2)change=0.056). The percentage of patients that was correctly classified increased from 56% to 62%; the net proportion of correct reclassifications 6% (95% CI 3 to 10%). The C-statistic increased from 0.78 to 0.82. Sensitivity analyses using imputation of missing radiographs yielded comparable results. CONCLUSIONS: Genetic risk factors together explained 12-18% of the variance in radiologic progression. Adding genetic factors improved the predictive accuracy, but 38% of the patients were still incorrectly classified, limiting the value for use in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND: The severity of radiologic progression is variable between rheumatoid arthritis (RA) patients. Recently, several genetic severity variants have been identified and were replicated, these belong to 12 loci. This study determined the contribution of the identified genetic factors to the explained variance in radiologic progression and whether genetic factors, in addition to traditional risk factors, improve the accuracy of predicting the severity of radiologic progression. METHODS: 426 early RApatients with yearly radiologic follow-up were studied. The main outcome measure was the progression in Sharp-van der Heijde score (SHS) over 6 years, assessed as continuous outcome or categorised in no/little, moderate or severe progression. Assessed were improved fit of a linear mixed model analysis on serial radiographs, R(2) using linear regression analyses, C-statistic and the net proportion of patients that was additionally correctly classified when adding genetic risk factors to a model consisting of traditional risk factors. RESULTS: The genetic factors together explained 12-18%. When added to a model including traditional factors and treatment effects, the genetic factors additionally explained 3-7% of the variance (p value R(2)change=0.056). The percentage of patients that was correctly classified increased from 56% to 62%; the net proportion of correct reclassifications 6% (95% CI 3 to 10%). The C-statistic increased from 0.78 to 0.82. Sensitivity analyses using imputation of missing radiographs yielded comparable results. CONCLUSIONS: Genetic risk factors together explained 12-18% of the variance in radiologic progression. Adding genetic factors improved the predictive accuracy, but 38% of the patients were still incorrectly classified, limiting the value for use in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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