A1 Refereed original research article in a scientific journal
Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB
Authors: Bicak M, Wang X, Gao XN, Xu X, Vaananen RM, Taimen P, Lilja H, Pettersson K, Klein RJ
Publisher: OXFORD UNIV PRESS
Publication year: 2020
Journal: Human Molecular Genetics
Journal name in source: HUMAN MOLECULAR GENETICS
Journal acronym: HUM MOL GENET
Volume: 29
Issue: 10
First page : 1581
Last page: 1591
Number of pages: 11
ISSN: 0964-6906
eISSN: 1460-2083
DOI: https://doi.org/10.1093/hmg/ddaa026
Self-archived copy’s web address: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526792/
Abstract
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.
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.
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