Quinn T Ostrom1, Jacob Edelson2,3, Jinyoung Byun1,2, Younghun Han1,2, Ben Kinnersley4, Beatrice Melin5, Richard S Houlston4, Michelle Monje6, Kyle M Walsh7,8, Christopher I Amos1,2, Melissa L Bondy1,9. 1. Department of Medicine, Section of Epidemiology and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA. 2. Institute for Clinical and Translational Research, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA. 3. Center for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, California, USA. 4. Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, London, UK. 5. Department of Radiation Sciences - Oncology, Umea University, Umea, Sweden. 6. Department of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, California, USA. 7. Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA. 8. Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA. 9. Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA.
Abstract
BACKGROUND: Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases. METHODS: Using summary statistics from a glioma genome-wide association studies (GWAS) meta-analysis, we identified significant enrichment for risk variants associated with gene expression changes in immune cell populations. We also estimated genetic correlations between glioma and autoimmune, atopic, and hematologic traits using linkage disequilibrium score regression (LDSC), which leverages genome-wide single-nucleotide polymorphism (SNP) associations and patterns of linkage disequilibrium. RESULTS: Nominally significant negative correlations were observed for glioblastoma (GB) and primary biliary cirrhosis (rg = -0.26, P = .0228), and for non-GB gliomas and celiac disease (rg = -0.32, P = .0109). Our analyses implicate dendritic cells (GB pHM = 0.0306 and non-GB pHM = 0.0186) in mediating both GB and non-GB genetic predisposition, with GB-specific associations identified in natural killer (NK) cells (pHM = 0.0201) and stem cells (pHM = 0.0265). CONCLUSIONS: This analysis identifies putative new associations between glioma and autoimmune conditions with genomic architecture that is inversely correlated with that of glioma and that T cells, NK cells, and myeloid cells are involved in mediating glioma predisposition. This provides further evidence that increased activation of the acquired immune system may modify individual susceptibility to glioma.
BACKGROUND: Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases. METHODS: Using summary statistics from a glioma genome-wide association studies (GWAS) meta-analysis, we identified significant enrichment for risk variants associated with gene expression changes in immune cell populations. We also estimated genetic correlations between glioma and autoimmune, atopic, and hematologic traits using linkage disequilibrium score regression (LDSC), which leverages genome-wide single-nucleotide polymorphism (SNP) associations and patterns of linkage disequilibrium. RESULTS: Nominally significant negative correlations were observed for glioblastoma (GB) and primary biliary cirrhosis (rg = -0.26, P = .0228), and for non-GB gliomas and celiac disease (rg = -0.32, P = .0109). Our analyses implicate dendritic cells (GB pHM = 0.0306 and non-GB pHM = 0.0186) in mediating both GB and non-GB genetic predisposition, with GB-specific associations identified in natural killer (NK) cells (pHM = 0.0201) and stem cells (pHM = 0.0265). CONCLUSIONS: This analysis identifies putative new associations between glioma and autoimmune conditions with genomic architecture that is inversely correlated with that of glioma and that T cells, NK cells, and myeloid cells are involved in mediating glioma predisposition. This provides further evidence that increased activation of the acquired immune system may modify individual susceptibility to glioma.
Authors: Qianghu Wang; Baoli Hu; Xin Hu; Hoon Kim; Massimo Squatrito; Lisa Scarpace; Ana C deCarvalho; Sali Lyu; Pengping Li; Yan Li; Floris Barthel; Hee Jin Cho; Yu-Hsi Lin; Nikunj Satani; Emmanuel Martinez-Ledesma; Siyuan Zheng; Edward Chang; Charles-Etienne Gabriel Sauvé; Adriana Olar; Zheng D Lan; Gaetano Finocchiaro; Joanna J Phillips; Mitchel S Berger; Konrad R Gabrusiewicz; Guocan Wang; Eskil Eskilsson; Jian Hu; Tom Mikkelsen; Ronald A DePinho; Florian Muller; Amy B Heimberger; Erik P Sulman; Do-Hyun Nam; Roel G W Verhaak Journal: Cancer Cell Date: 2017-07-10 Impact factor: 31.743
Authors: Corinna Seliger; Cristian Ricci; Christoph R Meier; Michael Bodmer; Susan S Jick; Ulrich Bogdahn; Peter Hau; Michael F Leitzmann Journal: Neuro Oncol Date: 2015-06-20 Impact factor: 12.300
Authors: Linden Disney-Hogg; Alex J Cornish; Amit Sud; Philip J Law; Ben Kinnersley; Daniel I Jacobs; Quinn T Ostrom; Karim Labreche; Jeanette E Eckel-Passow; Georgina N Armstrong; Elizabeth B Claus; Dora Il'yasova; Joellen Schildkraut; Jill S Barnholtz-Sloan; Sara H Olson; Jonine L Bernstein; Rose K Lai; Minouk J Schoemaker; Matthias Simon; Per Hoffmann; Markus M Nöthen; Karl-Heinz Jöckel; Stephen Chanock; Preetha Rajaraman; Christoffer Johansen; Robert B Jenkins; Beatrice S Melin; Margaret R Wrensch; Marc Sanson; Melissa L Bondy; Richard S Houlston Journal: BMC Med Date: 2018-03-15 Impact factor: 8.775
Authors: Jinyoung Byun; Younghun Han; Kyle M Walsh; Amy S Park; Melissa L Bondy; Christopher I Amos Journal: Sci Rep Date: 2022-02-03 Impact factor: 4.379