title: Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.
abstract: 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.
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas Carlsson
authors.initials: JC
authors.lastname: Almlöf
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Lundmark
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lundmark
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Canada.
authors.forename: Bing
authors.initials: B
authors.lastname: Ge
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Canada.
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.affiliation: Department of Cardiovascular Science, University of Leicester, Leicester, United Kingdom; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.affiliation: INSERM UMRS 937, Pierre and Marie Curie University and Medical School, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Heart Centre, Charterhouse Square London, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; National Health Service Blood and Transplant, Cambridge Centre, Long Road, Cambridge, United Kingdom.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
mesh_terms: D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D058977:Molecular Sequence Annotation; D009000:Monocytes / Q000378:metabolism*; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding