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rs2072135, a low-penetrance variant for chronic lymphocytic leukaemia?

Sava, Georgina P.; Speedy, Helen E.; Di Bernardo, Maria Chiara; Deaglio, Silvia; Karabon, Lidia; Frydecka, Irena; Woszczyk, Dariusz; Rossi, Davide; Gaidano, Gianluca and Mansouri, Larry, et al. (2013) In British Journal of Haematology 162(2). p.221-228
Abstract
Recent multi-stage genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are robustly associated with chronic lymphocytic leukaemia (CLL) risk. Given that most of these SNPs map to non-coding regions of the genome, it suggests that the functional basis of many GWAS signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (eQTL) data on lymphoblastoid cells lines (LCLs) we have globally demonstrated an association between GWAS P-values and eQTLs, consistent with much of the variation in CLL risk being defined by variants impacting on gene expression. To explore using eQTL data to select GWAS SNPs for replication, we genotyped... (More)
Recent multi-stage genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are robustly associated with chronic lymphocytic leukaemia (CLL) risk. Given that most of these SNPs map to non-coding regions of the genome, it suggests that the functional basis of many GWAS signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (eQTL) data on lymphoblastoid cells lines (LCLs) we have globally demonstrated an association between GWAS P-values and eQTLs, consistent with much of the variation in CLL risk being defined by variants impacting on gene expression. To explore using eQTL data to select GWAS SNPs for replication, we genotyped rs2072135 (GWAS P-value=00024, eQTL P-value=1510(-19)) in five independent case-control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined P-value=1x10(-4)), rs2072135 defines a promising risk locus for CLL. Incorporating eQTL information offers an attractive strategy for selecting SNPs from GWAS for validation. (Less)
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publication status
published
subject
keywords
chronic lymphocytic leukaemia, risk, polymorphism, gene expression
in
British Journal of Haematology
volume
162
issue
2
pages
221 - 228
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000321211300009
  • scopus:84879840126
ISSN
0007-1048
DOI
10.1111/bjh.12366
language
English
LU publication?
yes
id
def00a3e-bd4a-4efa-8fc5-555a8e276214 (old id 3975866)
date added to LUP
2013-09-02 07:35:02
date last changed
2019-02-20 02:39:04
@article{def00a3e-bd4a-4efa-8fc5-555a8e276214,
  abstract     = {Recent multi-stage genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are robustly associated with chronic lymphocytic leukaemia (CLL) risk. Given that most of these SNPs map to non-coding regions of the genome, it suggests that the functional basis of many GWAS signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (eQTL) data on lymphoblastoid cells lines (LCLs) we have globally demonstrated an association between GWAS P-values and eQTLs, consistent with much of the variation in CLL risk being defined by variants impacting on gene expression. To explore using eQTL data to select GWAS SNPs for replication, we genotyped rs2072135 (GWAS P-value=00024, eQTL P-value=1510(-19)) in five independent case-control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined P-value=1x10(-4)), rs2072135 defines a promising risk locus for CLL. Incorporating eQTL information offers an attractive strategy for selecting SNPs from GWAS for validation.},
  author       = {Sava, Georgina P. and Speedy, Helen E. and Di Bernardo, Maria Chiara and Deaglio, Silvia and Karabon, Lidia and Frydecka, Irena and Woszczyk, Dariusz and Rossi, Davide and Gaidano, Gianluca and Mansouri, Larry and Smedby, Karin E. and Juliusson, Gunnar and Rosenquist, Richard and Catovsky, Daniel and Houlston, Richard S.},
  issn         = {0007-1048},
  keyword      = {chronic lymphocytic leukaemia,risk,polymorphism,gene expression},
  language     = {eng},
  number       = {2},
  pages        = {221--228},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {rs2072135, a low-penetrance variant for chronic lymphocytic leukaemia?},
  url          = {http://dx.doi.org/10.1111/bjh.12366},
  volume       = {162},
  year         = {2013},
}