Nine residues in HLA-DQ molecules determine with susceptibility and resistance to type 1 diabetes among young children in Sweden.

ABSTRACT: HLA-DQ molecules account over 50% genetic risk of type 1 diabetes (T1D), but little is known about associated residues. Through next generation targeted sequencing technology and deep learning of DQ residue sequences, the aim was to uncover critical residues and their motifs associated with T1D. Our analysis uncovered (αa1, α44, α157, α196) and (β9, β30, β57, β70, β135) on the HLA-DQ molecule. Their motifs captured all known susceptibility and resistant T1D associations. Three motifs, "DCAA-YSARD" (OR = 2.10, p = 1.96*10^-20), "DQAA-YYARD" (OR = 3.34, 2.69*10^-72) and "DQDA-YYARD" (OR = 3.71, 1.53*10^-6) corresponding to DQ2.5 and DQ8.1 (the latter two motifs) associated with susceptibility. Ten motifs were significantly associated with resistance to T1D. Coll

SUBMITTER: Zhao LP 

PROVIDER: S-EPMC8065060 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature