Table 1.

Ewens-Watterson Homozygosity (EWH) test of neutrality at the HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1 loci based on the 4-field allele resolution level HLA genotyping data (and according to IPD-IMGT/HLA database version 3.25.0) of this Spanish population study.

Locus	Number of subjects typed (n)	k	Fo	Fe	Fnd	p-value of F
HLA-A	276	36	0.0983	0.1048	−0.1924	0.5208
HLA-B	276	53	0.0444	0.0661	−1.2197	0.0331*
HLA-C	276	40	0.0617	0.0934	−1.0858	0.0577
HLA-DPA1	275	14	0.1639	0.2766	−1.0498	0.0806
HLA-DPB1	274	29	0.1769	0.1336	0.9376	0.8572
HLA-DQA1	272	23	0.0872	0.1708	−1.3322	0.0094**
HLA-DQB1	269	24	0.0869	0.1630	−1.2857	0.0120*
HLA-DRB1	272	37	0.0733	0.1015	−0.8761	0.1443

The normalized deviate of the Ewens-Watterson homozygosity statistic (F_nd) was calculated based on the observed allele frequencies at each HLA locus and it is used to infer the action of balancing (F_nd << 0) or directional (F_nd >> 0) selection at each HLA locus. The results of the Ewens-Watterson Homozygosity Test are shown above. Number of unique alleles (k); Observed F (F_o); Expected F (F_e); Normalized deviate of F (F_nd).

^(*)p-value of F lower than 0.05 (p < 0.05) indicates a statistical significance at the 5% level.

^(**)p-value of F lower than 0.01 (p < 0.01) indicates a statistical significance at the 1% level.

Also when performing EWH test, HLA-DRB¾/5 loci were not included as they represent a particular virtual single “locus”. Where these HLA-DRB¾/5 genes characteristically behave as alleles of a single locus as the presence of one of these genes at the haplotype level excludes the presence of the other two genes. This is based on the linkage constraints that exist between the HLA-DRB¾/5 loci and the HLA-DRB1 locus, in which several HLA-DRB1 allele families can be differentiated [22].