Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms
| العنوان: | Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms |
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| المؤلفون: | 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 |
| المصدر: | e0123057 PLoS ONE |
| بيانات النشر: | PLoS, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | lipids (amino acids, peptides, and proteins) |
| الوصف: | 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. publishedVersion |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::0df0f1498069535893e6f05813101ff5Test https://hdl.handle.net/1956/9839Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.dedup.wf.001..0df0f1498069535893e6f05813101ff5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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