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Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB

Bicak, Mesude ; Wang, Xing ; Gao, Xiaoni ; Xu, Xing ; Väänänen, Riina Minna ; Taimen, Pekka ; Lilja, Hans LU ; Pettersson, Kim and Klein, Robert J. (2020) In Human Molecular Genetics 29(10). p.1581-1591
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
29
issue
10
pages
11 pages
publisher
Oxford University Press
external identifiers
  • pmid:32065238
  • scopus:85087320183
ISSN
0964-6906
DOI
10.1093/hmg/ddaa026
language
English
LU publication?
yes
id
df800c7f-5c1e-444d-8ee7-8754b51b1868
date added to LUP
2020-07-16 11:21:06
date last changed
2020-07-17 01:59:28
@article{df800c7f-5c1e-444d-8ee7-8754b51b1868,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Bicak, Mesude and Wang, Xing and Gao, Xiaoni and Xu, Xing and Väänänen, Riina Minna and Taimen, Pekka and Lilja, Hans and Pettersson, Kim and Klein, Robert J.},
  issn         = {0964-6906},
  language     = {eng},
  number       = {10},
  pages        = {1581--1591},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB},
  url          = {http://dx.doi.org/10.1093/hmg/ddaa026},
  doi          = {10.1093/hmg/ddaa026},
  volume       = {29},
  year         = {2020},
}