*Purpose: The RNA sequencing has the possibility of detecting overall gene expression as well as allele-specific expression. Here, we reported a study of genome-wide allele specific expression analysis of RNA sequencing profiles of pre-transplant blood in kidney transplant recipients to identify variant allele specific expression associated with graft loss.

*Methods: We genotyped 574 recipients using Exome DNA SNP array to generate typed and imputed exonic SNPs. We also performed RNA sequencing of the pre-transplant blood of 292 recipients to obtain additional exonic SNPs. We counted the reads covering variant and reference alleles respectively as allele-specific expression at each exonic SNP locus in 292 patients. We did association analysis of the both alleles with death censored graft loss (DCGL) using Cox model. We further investigated the identified association signals with single cell RNA sequencing of pretransplant PBMCs from 4 recipients.

*Results: We observed the expression of variant allele rather than reference allele at 605 SNP loci were significantly associated with DCGL (p <= 0.05), suggesting an allele-specific expression association with graft loss. The genes harboring those significant loci were enriched in the pathways of B cell receptor signaling pathway, hematopoietic cell lineage and antigen processing and presentation, among others. Interestingly, 19 out of the 605 significant loci were clustered in the Leukocyte Immunoglobulin-Like Receptors (LILRs) gene family which play a critical role in regulating immune response. The majority of these 19 exonic SNPs (12/19, 63%) are nonsynonymous in the signal-transducing cytoplasmic tail, implicating a functional role of LILR genes in graft loss by altering LILR protein function through the variants in immune response. The single cell sequencing data showed specific expression of LILR gene family in monocyte and dendritic cells and confirmed variant allele specific expression of LILR genes in the 2 patients with graft loss.

*Conclusions: Variant allele specific expression of LILR genes in pretransplant blood identifies kidney transplant patients at high risk of graft loss. The functional role of this variant allele expression in immune response regulation needs further investigation.

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