Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB
(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
- Bicak, Mesude ; Wang, Xing ; Gao, Xiaoni ; Xu, Xing ; Väänänen, Riina Minna ; Taimen, Pekka ; Lilja, Hans LU ; Pettersson, Kim and Klein, Robert J.
- organization
- publishing date
- 2020
- 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
-
- scopus:85087320183
- pmid:32065238
- 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
- 2024-08-22 00:39:11
@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 < 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}}, }