1. OR9 Multiethnic rna sequencing analysis of HLA reveals HLA-allele specific eQTLs
- Author
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Jill A. Hollenbach, Otto Jolanki, Paul Norman, Emmanuel Mignot, and Hanna Ollila
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Genetics ,Immunology ,Gene expression ,Immunology and Allergy ,RNA ,General Medicine ,Human leukocyte antigen ,Allele ,1000 Genomes Project ,Biology ,Gene ,Phenotype ,Histocompatibility - Abstract
Aim The HLA is major regulator for immune responses and several auto-immune or inflammatory diseases show a strong association with specific HLA alleles. However, it remains unclear what is the effect of individual HLA alleles on variation in cell phenotype and gene expression that potentially contribute to disease predisposition. Our aim was to characterize the role of individual HLA-alleles on gene expression over two ethnic groups and multiple populations. Methods We used RNA sequencing from lymphoblastoid cell lines, including HLA region, combined with HLA typing data from the 1000 genomes and Geuvadis projects in 462 individuals from European (CEPH, Finnish, British, Toscani) and African (Yoruba) populations. The analysis was normalized using PANAMA and analyzed with linear mixed model in R v3.2.0. Results The effect of HLA-alleles on gene expression revealed several genome-wide significant cis-eQTLs for other genes at the HLA region. Importantly, we also characterized several robust trans-eQTL signals for HLA class I and class II alleles ( P −8 ) that were enriched in genes mediating immune responses and shared among different populations. Conclusion HLA-alleles have a robust effect on gene expression and cellular phenotype that is shared across multiple populations.
- Published
- 2015
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