iKIR score decreases protection associated with protective class II genotypes in T1D.

The UK-GRID cohort without carriers of HLA class I drivers (N = 5,420) was stratified into individuals with high or low iKIR score at a 1.75 cutoff (we also tested cutoffs 1.5 and 2.0, see S5 Table). The protective effect of each genotype was evaluated independently in each stratum using multivariate logistic regression with gender as covariate. HLA class II protection is enhanced in the iKIR low strata for all genotypes but for the very infrequent protective genotype DQA1*02:01-DQB1*03:03. Regression coefficients, permutation p-values and cohort sizes are reported for the different strata. P-value for the whole cohort (unstratified analysis) calculated using the Wald-test; p-values for the stratification analysis are calculated using the permutation test.

本研究纳入未携带人类白细胞抗原I类（HLA class I）驱动变异的UK-GRID队列（UK-GRID cohort）个体共5420例，以1.75为截断值将其划分为iKIR评分（iKIR score）高、低两组；本研究同时测试了1.5与2.0作为截断值，详见补充表S5。针对各分层亚组，以性别作为协变量，采用多因素logistic回归分别独立评估每种基因型的保护效应。除极为罕见的保护性基因型DQA1*02:01-DQB1*03:03外，所有基因型的人类白细胞抗原II类（HLA class II）保护效应在iKIR评分低分组中均得到增强。本研究报告了不同分层亚组的回归系数、置换检验P值及队列样本量。全队列（未分层分析）的P值采用Wald检验（Wald-test）计算；分层分析的P值则采用置换检验（permutation test）计算。