Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms
dc.contributor.author | Andreassen, Ole Andreas | en_US |
dc.contributor.author | Desikan, Rahul S. | en_US |
dc.contributor.author | Wang, Yunpeng | en_US |
dc.contributor.author | Thompson, Wesley K. | en_US |
dc.contributor.author | Schork, Andrew J. | en_US |
dc.contributor.author | Zuber, Verena | en_US |
dc.contributor.author | Doncheva, Nadezhda T. | en_US |
dc.contributor.author | Ellinghaus, E.va | en_US |
dc.contributor.author | Mattingsdal, Morten | en_US |
dc.contributor.author | Franke, Andre | en_US |
dc.contributor.author | Lie, Benedicte. A. | en_US |
dc.contributor.author | Mills, Ian Geoffrey | en_US |
dc.contributor.author | Aukrust, Pål | en_US |
dc.contributor.author | McEvoy, Linda K. | en_US |
dc.contributor.author | Djurovic, Srdjan | en_US |
dc.contributor.author | Karlsen, Tom Hemming | en_US |
dc.contributor.author | Dale, Anders M. | en_US |
dc.date.accessioned | 2015-04-27T12:48:41Z | |
dc.date.available | 2015-04-27T12:48:41Z | |
dc.date.issued | 2015-04-08 | eng |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | https://hdl.handle.net/1956/9839 | |
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.iso | eng | eng |
dc.publisher | PLoS | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | eng |
dc.title | Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2015-04-15T13:24:49Z | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2015 Andreassen et al. | |
dc.source.articlenumber | e0123057 | |
dc.identifier.doi | https://doi.org/10.1371/journal.pone.0123057 | |
dc.identifier.cristin | 1237405 | |
dc.source.journal | PLoS ONE | |
dc.source.40 | 10 | |
dc.source.14 | 4 |