Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms

• Published in: PloS one Vol. 10; no. 4; p. e0123057
• Main Authors: Andreassen, Ole A, Desikan, Rahul S, Wang, Yunpeng, Thompson, Wesley K, Schork, Andrew J, Zuber, Verena, Doncheva, Nadezhda T, Ellinghaus, Eva, Albrecht, Mario, Mattingsdal, Morten, Franke, Andre, Lie, Benedicte A, Mills, Ian G, Mills, Ian, Aukrust, Pål, McEvoy, Linda K, Djurovic, Srdjan, Karlsen, Tom H, Dale, Anders M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.04.2015; Public Library of Science (PLoS)
• Subjects: Addictions; Analysis; Anti-inflammatory agents; Arthritis; Atherosclerosis; Autoimmune diseases; Autoimmune Diseases - blood; Autoimmune Diseases - genetics; Blood; Blood levels; Blood lipids; Cancer; Cardiovascular disease; Celiac disease; Cholesterol; Clinical medicine; Data processing; Density; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Dyslipidemia; Environmental factors; Epidemiology; Genetic aspects; Genetic Loci; Genetic Pleiotropy; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health risks; High density lipoprotein; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class II - genetics; Hospitals; Humans; Immunologic diseases; Inflammation; Inflammatory bowel diseases; Inflammatory Bowel Diseases - blood; Inflammatory Bowel Diseases - genetics; Informatics; Intestine; Laboratories; Lipids; Lipoproteins; Lipoproteins, HDL - blood; Lipoproteins, LDL - blood; Loci; Low density lipoprotein; Medical research; Medicine; Mental health; Metabolism; Metabolites; Molecular biology; Neurosciences; Pathogenesis; Pattern analysis; Physiological aspects; Pleiotropy; Polymorphism, Single Nucleotide; Psoriasis; Psychiatry; Psychosis; Rheumatoid arthritis; Risk factors; Risk sharing; Sarcoidosis; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Triglycerides; Triglycerides - blood; Ulcerative colitis; Norway; United States; La Jolla California; Austria; California; United States > US; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123057

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.