dc.date.accessioned | 2015-04-15T14:21:11Z | |
dc.date.available | 2015-04-15T14:21:11Z | |
dc.date.created | 2015-04-15T15:21:05Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Andreassen, Ole Andreas Desikan, RS Wang, Yunpeng Thompson, WK Schork, AJ Zuber, Verena Doncheva, NT Ellinghaus, E Mattingsdal, Morten Franke, A Lie, BA Mills, Ian Geoffrey Aukrust, Pål McEvoy, LK Djurovic, Srdjan Karlsen, TH Dale, AM . Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms. PLoS ONE. 2015 | |
dc.identifier.uri | http://hdl.handle.net/10852/43610 | |
dc.description.abstract | Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn’s disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents. | en_US |
dc.language | EN | |
dc.language.iso | en | en_US |
dc.publisher | Public Library of Science (PLoS) | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Andreassen, Ole Andreas | |
dc.creator.author | Desikan, RS | |
dc.creator.author | Wang, Yunpeng | |
dc.creator.author | Thompson, WK | |
dc.creator.author | Schork, AJ | |
dc.creator.author | Zuber, Verena | |
dc.creator.author | Doncheva, NT | |
dc.creator.author | Ellinghaus, E | |
dc.creator.author | Mattingsdal, Morten | |
dc.creator.author | Franke, A | |
dc.creator.author | Lie, BA | |
dc.creator.author | Mills, Ian Geoffrey | |
dc.creator.author | Aukrust, Pål | |
dc.creator.author | McEvoy, LK | |
dc.creator.author | Djurovic, Srdjan | |
dc.creator.author | Karlsen, TH | |
dc.creator.author | Dale, AM | |
cristin.unitcode | 185,53,10,70 | |
cristin.unitname | NORMENT part UiO | |
cristin.ispublished | false | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1237405 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS ONE&rft.volume=&rft.spage=&rft.date=2015 | |
dc.identifier.jtitle | PLoS ONE | |
dc.identifier.volume | 10 | |
dc.identifier.issue | 4 | |
dc.identifier.doi | 10.1371/journal.pone.0123057 | |
dc.identifier.urn | URN:NBN:no-47944 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1932-6203 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/43610/2/PLoS%2BOne.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | e0123057 | |