(GDR: gene detection rate, SV: surrogate variables). We estimated the effect of OUD vs. unaffected individuals across each annotated cell type, across neuronal subtypes (Neuron), across glial types (Glia), and across all cell types (All). For the first set of hypotheses at the annotated cell type level, we used the simple contrast CelltypeA_OUD_Sex?_Region? - CelltypeA_UC_Sex?_Region? with samples from both Sex and Regions to obtain the average effect across those variables (?, the wildcard placeholder for F, M, Caudate, or Putamen). For the second set hypotheses, we only included individuals within each Sex to obtain the effect of OUD vs. unaffected within each sex subset. For the third set of hypotheses, we use the following contrast: (CelltypeA_OUD_SexF_Region? - CelltypeA_UC_SexF_Region?) - (CelltypeA_OUD_SexM_Region? - CelltypeA_UC_SexM_Region?).