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dc.contributor.authorAndreassen, Ole Andreasen_US
dc.contributor.authorDesikan, Rahul S.en_US
dc.contributor.authorWang, Yunpengen_US
dc.contributor.authorThompson, Wesley K.en_US
dc.contributor.authorSchork, Andrew J.en_US
dc.contributor.authorZuber, Verenaen_US
dc.contributor.authorDoncheva, Nadezhda T.en_US
dc.contributor.authorEllinghaus, E.vaen_US
dc.contributor.authorMattingsdal, Mortenen_US
dc.contributor.authorFranke, Andreen_US
dc.contributor.authorLie, Benedicte. A.en_US
dc.contributor.authorMills, Ian Geoffreyen_US
dc.contributor.authorAukrust, Pålen_US
dc.contributor.authorMcEvoy, Linda K.en_US
dc.contributor.authorDjurovic, Srdjanen_US
dc.contributor.authorKarlsen, Tom Hemmingen_US
dc.contributor.authorDale, Anders M.en_US
dc.description.abstractEpidemiological 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.rightsAttribution CC BYeng
dc.titleAbundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanismsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2015 Andreassen et al.
dc.source.journalPLoS ONE

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