Open AccessProstate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB
Author(s) -
Mesude Bicak,
Xing Wang,
Xiaoping Gao,
Xianghua Xu,
Riina Minna Väänänen,
Pekka Taimen,
Hans Lilja,
Kim Pettersson,
Robert J. Klein
Publication year - 2020
Publication title -
human molecular genetics online/human molecular genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.811
H-Index - 276
eISSN - 1460-2083
pISSN - 0964-6906
DOI - 10.1093/hmg/ddaa026
Subject(s) - expression quantitative trait loci , biology , single nucleotide polymorphism , genome wide association study , snp , genetics , lncap , prostate cancer , locus (genetics) , linkage disequilibrium , carcinogenesis , allele , quantitative trait locus , genetic association , gene , cancer , genotype
How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.