Presentation Information
[OE7-3]Genetic correlation analysis provides novel insight into genetic background of human traits centralizing psoriasis
○Kotaro Ogawa1,2, Tsoi Lam3, Hiroaki Tanaka4, Masahiro Kanai5, Stuart Philip3, Nair Rajan3, Yoshiya Tanaka4, Hideki Mochizuki2, Elder James3, Yukinori Okada1,6,7,8 (1.Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan, 2.Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan, 3.University of Michigan Medical School, Ann Arbor, MI, USA., 4.The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, 5.Broad Institute of MIT and Harvard, USA, 6.Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan, 7.Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan, 8.Laboratory of Statistical Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan)
Epidemiological studies have reported comorbidity of psoriasis with many immune-related diseases, coronary artery disease, and metabolic traits. However, cross-trait relationship of genetic backgrounds between these traits and psoriasis has been elusive. Here, we collected the large-scale European-ancestry genome-wide association studies summary statistics of psoriasis and 21 traits and diseases, which have been reported to have close relationship to psoriasis in epidemiological studies. Then we conducted cross-trait genetic correlation analysis using LD score regression.
Pairwise genetic correlation analysis identified that coronary artery disease, immune-related diseases (Crohn's disease, ulcerative colitis, and schizophrenia), and metabolic traits (type 2 diabetes, body mass index, triglyceride, and HDL-cholesterol) were significantly associated with psoriasis. Cell-type specific analysis identified that CD4+CD25-IL17+PMA Ionomycin simulated Th17 primary cells are most significantly associated with psoriasis. Our study revealed such cell-type specificity by disentangling genetic links among psoriasis and relevant cell types without prior biologicalknowledge. Phenotype-cell type network analysis identified connections between allergic and autoimmune diseases and immune-related cell types, providing additional cell types contributing to psoriasis genetics.
Pairwise genetic correlation analysis identified that coronary artery disease, immune-related diseases (Crohn's disease, ulcerative colitis, and schizophrenia), and metabolic traits (type 2 diabetes, body mass index, triglyceride, and HDL-cholesterol) were significantly associated with psoriasis. Cell-type specific analysis identified that CD4+CD25-IL17+PMA Ionomycin simulated Th17 primary cells are most significantly associated with psoriasis. Our study revealed such cell-type specificity by disentangling genetic links among psoriasis and relevant cell types without prior biologicalknowledge. Phenotype-cell type network analysis identified connections between allergic and autoimmune diseases and immune-related cell types, providing additional cell types contributing to psoriasis genetics.