rs2072135, a low-penetrance variant for chronic lymphocytic leukaemia?
2013 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 162, no 2, 221-228 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 162, no 2, 221-228 p.
chronic lymphocytic leukaemia, risk, polymorphism, gene expression
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-204979DOI: 10.1111/bjh.12366ISI: 000321211300009OAI: oai:DiVA.org:uu-204979DiVA: diva2:641361