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 (CD). We hypothesized that overall IBD genetic risk, determined by IBD genetics 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 SNP genotypes were determined using the Immunochip and GRS were estimated by Mangrove. Results Among 157 Caucasian CGD patients 55 were confirmed, 78 excluded and 24 were uncertain for IBD. 201 established, independent European IBD risk SNPs passed quality control. After sample quality control and removing non-IBD CGD patients with perianal disease, mean GRS for 40 unrelated CGD-IBD patients was higher than 53 CGD non-IBD patients (in log2-scale 0.08±1.62 vs. −0.67±1.64, p=0.026) but lower than 239 IBD Genetics Consortium (IBDGC) young-onset CD 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 SNPs were nominally significant among CGD-IBD vs. CGD non-IBD, including those near LACC1 (p=0.005), CXCL14 (p=0.007) and TNFSF15 (p=0.016). Conclusions The weight of 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 non-syndromic pediatric CD, 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.

We performed 3D hydrodynamic simulations of the inner ≈ 50% radial extent of a 25 M⊙ star in the early phase of the main sequence and investigate core convection and internal gravity waves in the core-envelope boundary region. Simulations for different grid resolutions and driving luminosities establish scaling relations to constrain models of mixing for 1D applications. As in previous works, the turbulent mass entrainment rate extrapolated to nominal heating is unrealistically high (1.58 × 10−4 M⊙ yr−1), which is discussed in terms of the non-equilibrium response of the simulations to the initial stratification. We measure quantitatively the effect of mixing due to internal gravity waves excited by core convection interacting with the boundary in our simulations. The wave power spectral density as a function of frequency and wavelength agrees well with the GYRE eigenmode predictions based on the 1D spherically averaged radial profile. A diffusion coefficient profile that reproduces the spherically averaged abundance distribution evolution is determined for each simulation. Through a combination of eigenmode analysis and scaling relations it is shown that in the N2-peak region, mixing is due to internal gravity waves and follows the scaling relation DIGW-hydro∝L4/3 over a $\gtrapprox 2\,\,\mathrm{\mathrm{dex}}$ range of heating factors. Different extrapolations of the mixing efficiency down to nominal heating are discussed. If internal gravity wave mixing is due to thermally-enhanced shear mixing, an upper limit is $D_\mathrm{IGW}\lessapprox 2$ to 3 × 104 cm2/s at nominal heating in the N2-peak region above the convective core.

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