Genetic mapping of A-to-I RNA editing in human tissues links population variation and autoimmune disease

Speaker：Qin Li Ph.D，Stanford University, Department of Genetics

Title：Genetic mapping of A-to-I RNA editing in human tissues links population variation and autoimmune disease

Time：2019-4-10，10:00 AM

Place：Wangkezhen Building 348

Abstract:Adenosine-to-inosine (A-to-I) RNA editing plays a vital role in innate immunity, but its regulatory role and functional importance in disease pathogenesis remain largely unclear. Here we mapped the cis-regulatory variants of A-to-I RNA editing (edQTLs) in 49 human tissues from 934 individuals and found that almost ten thousand edited genes were subjected to genetic regulation. edQTLs distribution in Alu repeats aligned with the binding signature of ADAR protein and explained up to 70% of editing level variation. By fine-mapping with disease and complex trait GWAS, we found that edQTLs were strongly enriched in autoimmune and coronary-artery diseases, prevailing over expression and splicing QTLs. Moreover, 40-50% of the phenotype heritability of autoimmune diseases was explained by edQTLs and the partitioned heritability was more than 10-fold enriched over expression QTLs in predicted immunogenic RNA regions. Colocalization analysis pinpointed 25 loci shared between edQTLs and autoimmune disease GWAS signal. Interestingly, the top colocalization signals resided mostly in intermolecular double-stranded RNAs formed by proximal anti-sense transcripts. Our findings illustrate widespread genetic regulation of RNA editing in human tissues, and shed light onto RNA editing-mediated mechanisms in autoimmune disease etiology.