PMID- 23818875
OWN - NLM
STAT- MEDLINE
DCOM- 20130910
LR  - 20211021
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 9
IP  - 6
DP  - 2013 Jun
TI  - DeepSAGE reveals genetic variants associated with alternative polyadenylation and 
      expression of coding and non-coding transcripts.
PG  - e1003594
LID - 10.1371/journal.pgen.1003594 [doi]
LID - e1003594
AB  - Many disease-associated variants affect gene expression levels (expression 
      quantitative trait loci, eQTLs) and expression profiling using next generation 
      sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 
      94 total blood samples from healthy volunteers with DeepSAGE to gain specific 
      insight into how genetic variants affect the expression of genes and lengths of 
      3'-untranslated regions (3'-UTRs). We detected previously unknown cis-eQTL 
      effects for GWAS hits in disease- and physiology-associated traits. Apart from 
      cis-eQTLs that are typically easily identifiable using microarrays or 
      RNA-sequencing, DeepSAGE also revealed many cis-eQTLs for antisense and other 
      non-coding transcripts, often in genomic regions containing 
      retrotransposon-derived elements. We also identified and confirmed SNPs that 
      affect the usage of alternative polyadenylation sites, thereby potentially 
      influencing the stability of messenger RNAs (mRNA). We then combined the power of 
      RNA-sequencing with DeepSAGE by performing a meta-analysis of three datasets, 
      leading to the identification of many more cis-eQTLs. Our results indicate that 
      DeepSAGE data is useful for eQTL mapping of known and unknown transcripts, and 
      for identifying SNPs that affect alternative polyadenylation. Because of the 
      inherent differences between DeepSAGE and RNA-sequencing, our complementary, 
      integrative approach leads to greater insight into the molecular consequences of 
      many disease-associated variants.
FAU - Zhernakova, Daria V
AU  - Zhernakova DV
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Genetics, Groningen, The Netherlands.
FAU - de Klerk, Eleonora
AU  - de Klerk E
FAU - Westra, Harm-Jan
AU  - Westra HJ
FAU - Mastrokolias, Anastasios
AU  - Mastrokolias A
FAU - Amini, Shoaib
AU  - Amini S
FAU - Ariyurek, Yavuz
AU  - Ariyurek Y
FAU - Jansen, Rick
AU  - Jansen R
FAU - Penninx, Brenda W
AU  - Penninx BW
FAU - Hottenga, Jouke J
AU  - Hottenga JJ
FAU - Willemsen, Gonneke
AU  - Willemsen G
FAU - de Geus, Eco J
AU  - de Geus EJ
FAU - Boomsma, Dorret I
AU  - Boomsma DI
FAU - Veldink, Jan H
AU  - Veldink JH
FAU - van den Berg, Leonard H
AU  - van den Berg LH
FAU - Wijmenga, Cisca
AU  - Wijmenga C
FAU - den Dunnen, Johan T
AU  - den Dunnen JT
FAU - van Ommen, Gert-Jan B
AU  - van Ommen GJ
FAU - 't Hoen, Peter A C
AU  - 't Hoen PA
FAU - Franke, Lude
AU  - Franke L
LA  - eng
GR  - RC2 MH089951/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20130620
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Retroelements)
SB  - IM
EIN - PLoS Genet. 2013 Sep;9(9). doi: 
      10.1371/annotation/296056cb-f80c-4b04-985b-180f6d3cc4ae
MH  - 3' Untranslated Regions/genetics
MH  - Gene Expression Regulation/*genetics
MH  - Genome-Wide Association Study
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Polyadenylation/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Quantitative Trait Loci/*genetics
MH  - Retroelements/*genetics
PMC - PMC3688553
COIS- The authors have declared that no competing interests exist.
EDAT- 2013/07/03 06:00
MHDA- 2013/09/11 06:00
PMCR- 2013/06/01
CRDT- 2013/07/03 06:00
PHST- 2013/04/12 00:00 [received]
PHST- 2013/05/10 00:00 [accepted]
PHST- 2013/07/03 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2013/09/11 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - PGENETICS-D-13-00977 [pii]
AID - 10.1371/journal.pgen.1003594 [doi]
PST - ppublish
SO  - PLoS Genet. 2013 Jun;9(6):e1003594. doi: 10.1371/journal.pgen.1003594. Epub 2013 
      Jun 20.