Table 4. Interactions underlying HLA class I disease associations in Crohn’s disease cases.

AH8.1 is associated with increased odds of good prognosis amongst Crohn’s disease cases. In our cohort two classical HLA class I alleles from this haplotype, B*08:01 and C*07:01 are associated with good prognosis (Appendix 3—table 7). For both B*08:01 and C*07:01 we sought to determine the underlying mechanism by performing 5 multivariate linear regressions (model 2–6), one for each of the distance metrics. The coefficient (Coeff) and P value for the index allele and the similarity metric are recorded below. Gender was included as an additional covariate in all models. A coefficient <0 indicates a protective effect (P, decreased odds of poor prognosis), a coefficient >0 indicates a detrimental effect (D, increased odds of poor prognosis). Despite good power, similar alleles by all 5 metrics were never significantly protective (indeed in some cases tended towards being detrimental e.g. similar alleles by TCR or LILRB1 binding). Inclusion of 3 non-MHC SNPs which were significant in a GWAS as covariates did not alter these conclusions. Significance codes: p<0.001 ***; p<0.01 **; p<0.05 *; p<0.1. ; P values are two tailed.

			Index allele
Model		COV.		B*08:01	C*07:01
1. Index only		index	Coeff	−0.50 P	−0.34 P
			P val	3.56 × 10−7 ****	0.0003 ***
2. Index+TCR.FS		Index	Coeff	−0.49	−0.34
			P val	9.96 × 10−7 ****	0.0008 ***
		TCR.FS	Coeff	0.65 D	0.041 D
			P val	0.20	0.84
3. Index+iKIR.FS		Index	Coeff	−0.50	−0.34
			P val	3.75 × 10−7 ****	0.0007 ***
		iKIR.FS	Coeff	−0.08 P	0.02 D
			P val	0.89	0.86
4. Index+aKIR.FS		Index	Coeff	−0.50	−0.34
			P val	3.56 × 10−7 ****	0.0003 ***
		aKIR.FS	Coeff	0	0.001 D
			P val	1	0.99
5. Index+LILRB1.S		Index	Coeff	−0.50	−0.28
			P val	1.46 × 10−6 ****	0.007 **
		LILRB1.S	Coeff	−0.001 P	0.28 D
			P val	1	0.09 .
6. Index+LILRB2.S		Index	Coeff	−0.50	−0.28
			P val	2.28 × 10−6 ****	0.007 **
		LILRB2.S	Coeff	0.007 P	0.28 P
			P val	0.98	0.11