Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.

Almlöf, Jonas Carlsson; Lundmark, Per; Lundmark, Anders; Ge, Bing; Pastinen, Tomi; Cardiogenics Consortium; Goodall, Alison H; Cambien, François; Deloukas, Panos; Ouwehand, Willem H; Syvänen, Ann-Christine; Schunkert, Heribert; Attwood, Tony; Belz, Stephanie; Braund, Peter; Brocheton, Jessy; Cooper, Jason; Crisp-Hihn, Abi; Diemert, Patrick; Erdmann, Jeanette; Foad, Nicola; Godefroy, Tiphaine; Gracey, Jay; Gray, Emma; Gwilliams, Rhian; Heimerl, Susanne; Hengstenberg, Christian; Jolley, Jennifer; Krishnan, Unni; Lloyd-Jones, Heather; Liljedahl, Ulrika; Lugauer, Ingrid; Maouche, Seraya; Moore, Jasbir S; Montalescot, Gilles; Muir, David; Murray, Elizabeth; Nelson, Chris P; Neudert, Jessica; Niblett, David; O'Leary, Karen; Pollard, Helen; Proust, Carole; Rankin, Angela; Rendon, Augusto; Rice, Catherine M; Sager, Hendrik; Samani, Nilesh J; Sambrook, Jennifer; Schunkert, Heribert; Schmitz, Gerd; Scholz, Michael; Schroeder, Laura; Stephens, Jonathan; Tennstedt, Stefanie; Wallace, Chris     «

Almlöf, Jonas Carlsson; Lundmark, Per; Lundmark, Anders; Ge, Bing; Pastinen, Tomi; Cardiogenics Consortium; Goodall, Alison H; Cambien, François; Deloukas, Panos; Ouwehand, Willem H; Syvänen, Ann-Christine; Schunkert, Heribert; Attwood, Tony; Belz, Stephanie; Braund, Peter; Brocheton, Jessy; Cooper, Jason; Crisp-Hihn, Abi; Diemert, Patrick; Erdmann, Jeanette; Foad, Nicola; Godefroy, Tiphaine; Gracey, Jay; Gray, Emma; Gwilliams, Rhian; Heimerl, Susanne; Hengstenberg, Christian; Jolley, Jennifer;...     »

We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding genes. Focusing on the intergenic regions, and using stringent analysis of the allele-specific expression data, we detected robust cis-regulatory SNPs in 258 out of 489 informative intergenic regions included in the analysis. The cis-regulatory SNPs that were significantly associated with allele-specific expression of long non-coding RNAs were enriched to enhancer regions marked for active or bivalent, poised chromatin by histone modifications. Out of the lncRNA regions regulated by cis-acting regulatory SNPs, 20% (n = 52) were co-regulated with the closest protein coding gene. We compared the identified cis-regulatory SNPs with those in the catalog of SNPs identified by genome-wide association studies of human diseases and traits. This comparison identified 32 SNPs in loci from genome-wide association studies that displayed a strong association signal with allele-specific expression of non-coding RNAs in monocytes, with p-values ranging from 6.7×10(-7) to 9.5×10(-89). The identified cis-regulatory SNPs are associated with diseases of the immune system, like multiple sclerosis and rheumatoid arthritis.     «

We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding gene...     »