As individual amino acids coded by the HLA genes have been previously indicated to drive disease association,27, 28 we examined whether the associations of the top SNPs could be explained by individual coding polymorphisms at the HLA-DRB1 or DQA1 alleles (Supplementary Table 3). The DRB1 position 11 V was observed with the strongest protection for ASPD (OR=0.49 (0.37–0.66), P=2.4 × 10−6). Interestingly, DRB1 position 11 V is detected here with those DRB1*04 alleles that were associated at the allele level. In addition, DRB1 position 11 V was in relatively high LD with rs2395163 (D′=0.83, r2=0.56). Conditioning for position 11 V removed the association with rs2395163, but not with the leading variant at the HLA region (rs9268528 conditioned P=8.3 × 10−3) or with DRB1*01:01 (conditioned P=5.2 × 10−4), which was the strongest association at the HLA-region after conditioning for DRB1 position 11 V. Finally, we studied whether DRB1 position 11 V, together with HLA-DRB1*01:01, would explain the association with rs9268528. This was not the case. Even though the P-value for rs9268528 association was weaker after conditioning for both HLA-DRB1*01:01 and for DRB1 position 11 V, it was still significant with a point-wise P-value<0.05.
