RT Journal
A1 Cao, Shuo
A1 Zhu, Haoran
A1 Cui, Jinru
A1 Liu, Sun
A1 Li, Yuhe
A1 Shi, Junfang
A1 Mo, Junyuan
A1 Wang, Zihan
A1 Wang, Hailan
A1 Hu, Jiaxin
A1 Chen, Lizhi
A1 Li, Yuan
A1 Xia, Laixin
A1 Xiao, Shan
T1 Allele-specific RNA N6-methyladenosine modifications reveal functional genetic variants in human tissues
JF Genome Research 
JO Genome Research 
YR 2023 
FD August 01 
VO 33 
IS 8 
SP 1369 
OP 1380 
DO 10.1101/gr.277704.123 
UL http://genome.cshlp.org/content/33/8/1369.abstract 
AB An intricate network of cis- and trans-elements acts on RNA N6-methyladenosine (m6A), which in turn may affect gene expression and, ultimately, human health. A complete understanding of this network requires new approaches to accurately measure the subtle m6A differences arising from genetic variants, many of which have been associated with common diseases. To address this gap, we developed a method to accurately and sensitively detect transcriptome-wide allele-specific m6A (ASm6A) from MeRIP-seq data and applied it to uncover 12,056 high-confidence ASm6A modifications from 25 human tissues. We also identified 1184 putative functional variants for ASm6A regulation, a subset of which we experimentally validated. Importantly, we found that many of these ASm6A-associated genetic variants were enriched for common disease–associated and complex trait–associated risk loci, and verified that two disease risk variants can change m6A modification status. Together, this work provides a tool to detangle the dynamic network of RNA modifications at the allelic level and highlights the interplay of m6A and genetics in human health and disease.