Adler et. al.
NOD2 predicting Crohn’s phenotype meta-analysis
Supplemental materials
Supplementary Figure 1
Graphic representation of QUADAS criteria for assessment of publication quality. Bars
represent percent of publications fulfilling criteria in each category. Papers with
inadequate documentation of these criteria are may introduce an increased risk for bias.
Supplementary Figure 2
Forest plots of relative risk (A) and sensitivity and specificity (B) of one mutant NOD2
allele for complicated disease. There was little heterogeneity between studies (I2=44.6%;
Cochran’s Q=18.4, p=0.05). RR, risk ratio; CI, confidence interval, B1, inflammatory;
B2, structuring; B3, fistulizing phenotypes.
Supplementary Figure 3
Forest plots of relative risk (A) and sensitivity and specificity (B) of two mutant NOD2
alleles. There was moderate heterogeneity between studies (I2=55.0%; Cochran’s
Q=12.5, p=0.2). RR, risk ratio; CI, confidence interval, B1, inflammatory; B2,
structuring; B3, fistulizing phenotypes.
Supplementary Figure 4
Forest plots of relative risk (A) and sensitivity and specificity (B) for the presence of any
homozygous NOD2 mutant allele. There was substantial heterogeneity between studies
(I2= 93.8%; Cochran’s Q=4.5, p=0.2). RR, risk ratio; CI, confidence interval, B1,
inflammatory; B2, structuring; B3, fistulizing phenotypes.
Supplementary Figure 5
Forest plots of relative risk for complicated disease in the presence of p.R702W (A),
p.G908R (B), and p.Leu1007fsX1008 (C) mutant allele. RR, risk ratio; CI, confidence
interval, B1, inflammatory; B2, structuring; B3, fistulizing phenotypes.
Supplementary Figure 6
Forest plots of relative risk for perianal disease in the presence of p.R702W (A),
p.G908R (B), and p.Leu1007fsX1008 (C) mutant allele. RR, risk ratio; CI, confidence
interval, B1, inflammatory; B2, structuring; B3, fistulizing phenotypes.
Supplementary Figure 7
Summary receiver operating characteristics (ROC) curves for the presence of one or more
NOD2 mutant alleles as a predictor of stricturing (A), and fistulizing (B) Crohn’s disease
phenotypes and surgery (C) for Crohn’s disease. The AuROC curve is 0.61 for stricturing
disease, 0.54 for fistulizing disease, and 0.63 for surgery, consistent with low prognostic
accuracy for each.
Supplementary Figure 8
Summary receiver operating characteristics (ROC) curves (A) for the presence of
homozygous p.Leu1007fsX1008 mutant alleles as a predictor of complicated disease.
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Adler et. al.
NOD2 predicting Crohn’s phenotype meta-analysis
The AuROC curve is 0.98 for complicated disease, consistent with high prognostic
accuracy. Likelihood ratio (LR) scatterplot matrix (B) of the presence of homozygous
p.Leu1007fsX1008 mutant alleles associated with complicated disease. The summary
LR point is represented by the shaded rhomboid. The bars represent the 95% confidence
intervals. All 5 studies are in the right lower quadrant providing neither exclusion nor
confirmation, demonstrating that homozygous p.Leu1007fsX1008 mutant alleles are
weak predictors of complicated disease phenotype. The positive likelihood ratio (LRP) is
2.6 (95% CI 0.4 to 16.6), and negative likelihood ratio (LRN) is 0.98 (95% CI 0.94 to
1.03) making p.Leu1007fsX1008 highly specific, but poorly sensitive for predicting
complicated disease. LUQ, left upper quadrant; RUQ, right upper quadrant; LLQ, left
lower quadrant; RLQ, right lower quadrant.
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