Table 3.
OR calculations for 3 NOD2 CD risk alleles (p.R702W, p.G908R, p.L1007fs), composite, and compound heterozygous combinations in the DiscovEHR cohort.
| NOD2 variant | DiscovEHR MAF | DiscovEHR controls (N = 50,305) | DiscovEHR IBD cases (N = 984) | Additive model OR [95% CI] (P-value) | Genotypic model (heterozygous) OR [95% CI] (P-value) | Genotypic model (homozygous) OR [95% CI] (P-value) | Recessive model OR [95% CI] (P-value) | ExAC MAF | IBD exomes OR (P-value) |
|---|---|---|---|---|---|---|---|---|---|
| p.R702W | 0.050 | Het = 4727; Hom = 145 | Het = 116; Hom = 11 | 1.43 [1.20–1.71] (4.63 × 10–5) | 1.30 [1.06–1.58] (0.008765) | 4.02 [2.17–7.45] (6.86 × 10–6) | 3.91 [2.11–7.24] (2.86 × 10–6) | 0.035 | 1.92 (< 1 × 10–16) |
| p.G908R | 0.017 | Het = 1683; Hom = 16 | Het = 52; Hom = 0 | 1.56 [1.18–2.06] (0.001544) | 1.61 [1.21–2.13] (0.00087) | NA | NA | 0.012 | 1.91 (< 1 × 10–16) |
| p.L1007fs | 0.029 | Het = 2808; Hom = 42 | Het = 86; Hom = 8 | 1.84 [1.50–2.26] (1.69 × 10–9) | 1.63 [1.30–2.04] (1.67 × 10–5) | 10.15 [4.75–21.69] (1.38 × 10–12) | 9.80 [4.59–20.94] (3.80 × 10–13) | 0.018 | 2.57 (< 1 × 10–16) |
| Compound Het | N = 263 | N = 22 | 4.35 [2.80–6.75] (8.14 × 10–13) | ||||||
| Composite NOD2 | Het = 8955; Rec = 450 | Het = 232; Rec = 41 | 1.64 [1.45–1.86] (4.58 × 10–15) | 1.49 [1.28–1.73] (2.75 × 10–7) | 5.24 [3.77–7.27] (4.31 × 10–22) | 4.81 [3.47–6.67] (1.63 × 10–25) | |||
| 3.29 [2.56–4.23] (2 alleles predicted) |
There were no homozygotes for the p.G908R variant affected with IBD in our cohort; therefore, no genotypic homozygous and recessive ORs could be calculated. The ‘Composite NOD2′ calculations account for all alleles and genotypes for the 3 CD risk variants in the different genetic models.