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. 2016 Dec;22(12):2794-2801.
doi: 10.1097/MIB.0000000000000966.

Genetic Risk for Inflammatory Bowel Disease Is a Determinant of Crohn's Disease Development in Chronic Granulomatous Disease

Free PMC article

Genetic Risk for Inflammatory Bowel Disease Is a Determinant of Crohn's Disease Development in Chronic Granulomatous Disease

Chengrui Huang et al. Inflamm Bowel Dis. .
Free PMC article


Background: Approximately, one-third to one-half of children with chronic granulomatous disease (CGD) develop gastrointestinal inflammation characteristic of idiopathic inflammatory bowel disease (IBD), usually Crohn's disease. We hypothesized that the overall IBD genetic risk, determined by IBD genetic risk score (GRS), might in part determine IBD development in CGD.

Methods: We reviewed medical records to establish IBD diagnoses in CGD subjects seen at NIAID. IBD risk single nucleotide polymorphism genotypes were determined using the Immunochip, and GRS were estimated by Mangrove.

Results: Among 157 white patients with CGD, 55 were confirmed, 78 excluded, and 24 were uncertain for IBD. Two hundred one established, independent European IBD risk single nucleotide polymorphisms passed quality control. After sample quality control and removing non-IBD CGD patients with perianal disease, mean GRS for 40 unrelated patients with CGD-IBD was higher than 53 CGD non-IBD patients (in log2-scale 0.08 ± 1.62 versus -0.67 ± 1.64, P = 0.026) but lower than 239 IBD Genetics Consortium (IBDGC) young-onset Crohn's disease cases (0.76 ± 1.60, P = 0.025). GRS for non-IBD CGD was similar to 609 IBDGC controls (-0.69 ± 1.60, P = 0.95). Seven established IBD single nucleotide polymorphisms were nominally significant among CGD-IBD versus CGD non-IBD, including those near LACC1 (P = 0.005), CXCL14 (P = 0.007), and TNFSF15 (P = 0.016).

Conclusions: The weight of the common IBD risk alleles are significant determinants of IBD in CGD. However, IBD risk gene burden among CGD children with IBD is significantly lower than that in nonsyndromic pediatric Crohn's disease, congruent with the concept that defective superoxide production in CGD is also a major IBD risk factor. Individual IBD genes might interact with the CGD defect to cause IBD in CGD.

Conflict of interest statement

No authors have conflicts of interest to declare.


Figure 1
Figure 1
Comparisons of mean IBD genetic risk scores (GRSs) in log2 scale among 609 IBDGC healthy controls (IBDGC Ctrl), 53 CGD patients without IBD (CGD no IBD), 40 CGD patients with IBD (CGD IBD), and 239 IBDGC young-onset CD cases (IBDGC CD YO)
Figure 2
Figure 2
Histograms showing distributions of IBD genetic risk scores (GRSs) in log2 scale for four sets of study subjects: IBDGC healthy controls and IBDGC Crohn’s disease Young Onset (left side), and CGD-no IBD and CGD-IBD (right side).

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