Publication Date:
2013-11-15
Description:
Genomewide association studies (GWAS) have identified seven independent regions associated with Multiple Myeloma (MM) risk with an additional locus linked to the t11;14 subtype. Inherited variation is an important determinant of gene expression, such that the majority of published GWAS risk loci across all diseases can be linked to gene regulation. To understand whether the functional mechanisms that confer MM risk are related to allelic differences within regulatory regions, we sought to identify expression quantitative trait loci (eQTLs) in MM plasma cells. Recent studies have also suggested that eQTLs can be specific to cell type. In a heterogeneous disease such as MM, we might expect there to be variation in eQTLs between cytogenetic subgroups. To address this, we performed a genomewide analysis to identify MM related eQTLs, as well as potential subgroup specific MM eQTLs. The identification of eQTLs specific to MM plasma cells provides a means to link regulatory function to the powerful hypothesis-free tool of GWAS. To generate MM related eQTLs, we combined orthogonal mRNA expression data (Affymetrix U133+2 arrays) from CD138+ selected plasma cells with genotyping data (Illumina Omni Express BeadChips) from germline DNA in the same individual. Two independent datasets comprising 183 MM patients from UK and 662 from Germany were analysed in parallel. Genotype data was filtered by standard quality control parameters. Single nucleotide polymorphisms (SNPs) showing deviation from Hardy-Weinberg equilibrium with P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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